BASIC SCIENCE
Europace (2017) 0, 1–10 doi:10.1093/europace/euw375
The effect of left ventricular pacing on transmural activation delay in myopathic human hearts nchez†, Paul Angaran†, Ste´phane Masse´, Krishnakumar Nair, Andreu Porta-Sa Talha Farid, Karthikeyan Umapathy, John Asta, Sigfus Gizurarson, and Kumaraswamy Nanthakumar* The Hull Family Cardiac Fibrillation Management Laboratory, University Health Network, Toronto General Hospital, 150 Gerrard Street West, Gerrard Wing, 3-526, Toronto, ON, Canada M5G 2C4 Received 13 July 2016; accepted after revision 22 October 2016
Aims
Left ventricular (LV) epicardial pacing (LVEpiP) in human myopathic hearts does not decrease global epicardial activation delay compared with right ventricular (RV) endocardial pacing (RVEndoP); however, the effect on transmural activation delay has not been evaluated. To characterize the transmural electrical activation delay in human myopathic hearts during RVEndoP and LVEpiP compared with global epicardial activation delay.
................................................................................................................................................................................................... Methods Explanted hearts from seven patients (5 male, 46 ± 10 years) undergoing cardiac transplantation were Langendorff-perfused and mapped using an epicardial sock electrode array (112 electrodes) and 25 transmural plunge needles (four electrodes, and results
2 mm spacing), for a total of 100 unipolar transmural electrodes. Electrograms were recorded during LVEpiP and RVEndoP, and epicardial (sock) and transmural (needle) activation times, along with patterns of activation, were compared. There was no difference between the global epicardial activation times (LVEpiP 147 ± 8 ms vs. RVEndoP 156± 17 ms, P = 0.46). The mean LV transmural activation time during LVEpiP was significantly shorter than that during RVEndoP (125 ± 44 vs. 172± 43 ms, P < 0.001). During LVEpiP, of the transmural layers endo-, mid-myocardium and epicardium, LV endocardial layer was often the earliest compared with other transmural layers.
................................................................................................................................................................................................... Conclusion In myopathic human hearts, LVEpiP did not decrease global epicardial activation delays compared with RVEndoP.
LV epicardial pacing led to early activation of the LV endocardium, revealing the importance of the LV endocardium even when pacing from the LV epicardium. 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏
Keywords
Electrophysiology
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Pacing
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Transmural activation
Introduction It is assumed that left ventricular (LV) pacing will produce greater electrical synchrony to ventricles with LBBB and electrical dyssynchrony. When Leclercq et al.1 used a high-density epicardial sock and measured electrical synchrony, surprisingly, LV epicardial pacing (LVEpiP) did not result in reduction in electrical dyssynchrony compared with LBBB. It is also known that epicardial activation best reflects surface ECG duration.2 Thus, it is no surprise that not all CRT
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Electrical dyssynchrony
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Langendorff
series have described QRS narrowing after CRT implantation as a predictor of response. In fact, many patients have a clinical and mechanical response despite the absence of QRS duration shortening.3 This has also been described in patients upgraded from a chronic right ventricular (RV) pacing system to a biventricular device.4 An explanation as to why some patients experience a clear benefit from LVEpiP, despite the lack of reduction in QRS duration or epicardial activation delay, is not known.
* Corresponding author. Tel: þ1 416 340 4442; fax: þ1 416 340 4457. E-mail address:
[email protected] †
The first two authors contributed equally to the study.
C The Author 2017. For permissions, please email:
[email protected]. Published on behalf of the European Society of Cardiology. All rights reserved. V
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A. Porta-Sanchez et al.
What’s new? • An in-depth evaluation of the transmural myocardial activation during left ventricular (LV) epicardial pacing vs. right ventricular (RV) endocardial pacing is presented. • Transmural activation times during LV epicardial pacing are shorter compared with RV endocardial pacing. • The LV epicardial pacing leads to rapider penetration into the LV endocardium compared with RV endocardial pacing.
Assessment of the electrical resynchronization with LV pacing has been studied with QRS duration and epicardial activation mapping tools, but a thorough evaluation of the involvement of the various myocardial layers, especially the transmural layer is lacking. More importantly, the sequence of activation of the various layers during RV endocardial pacing (RVEndoP) and LVEpiP is not known. It thus appears an important aspect of LV electrical activation is not being evaluated. One such important aspect is the transmural activation delay of the LV. This region of the myocardium has not been mapped in humans for obvious ethical concerns of plunging needle electrodes into myocardium. Our human Langendorff programme affords us the unique opportunity to study these transmural activation patterns in humans, specifically in cardiomyopathic patients, with commonly used pacing sites.5–7 We sought to study the transmural electrical activation delay, in the various layers of the myocardium, specifically the epicardium, mid-myocardium and endocardium in myopathic human hearts, during LVEpiP compared with RV pacing modality. We compared activation delay especially during RVEndoP and LVEpiP. The objective of this study was to characterize the electrical activation patterns in human myopathic hearts during RVEndoP and LVEpiP. We hypothesized that the LVEpiP-generated wavefront will produce less transmural electrical delay without altering global epicardial delay compared with the RVEndoP-generated wavefront.
Methods Protocol This protocol was approved by the University Health Network Research Ethics Board and informed consent was obtained from each patient. The hearts studied were explanted from seven cardiomyopathic patients undergoing orthotopic heart transplantation. The methods have been described by our group previously.7 Once the preparation was stabilized for 10 min, the mapping protocol was completed within 30 min. Each heart was paced from the RV endocardium using a pacing needle at the apex, and from the LV epicardium using a hook electrode on the posterolateral wall; the LVepiP site was then confirmed to have an acceptable pacing threshold, or the hook electrode would be repositioned as needed. The hearts were paced at cycle length of 600 ms at twice the diastolic threshold for 2 min and 1:1 capture was verified. There was a minimum interval of 5 min between pacing from each site. Electrograms were recorded during RVEndoP and LVEpiP.
Mapping tools An epicardial sock electrode array was used to map the ventricular epicardium (Figure 1A and B). The sock is made up of 112 unipolar electrodes
organized in 14 rows of eight electrodes each, mounted on an extensible mesh. Unipolar signal electrograms were recorded and used to determine local activation times (LATs). Unipolar plunge needles were constructed using a modified version of a previously described method.8,9 Twenty-five plunge needles were constructed using 13 mm, 21 gauge stainless steel needles (Figure 1C and D). Four 36-gauge silver electrodes were spaced 2 mm apart along the length of each needle, so that there were a total of 100 electrodes. The needles were inserted as five rows of five needles, starting between rows 1 and 2 on the epicardial sock and ending between rows 5 and 6, arranged in a grid formation covering the entire LV except for the septum.
Data acquisition and analysis Data acquisition and filtering has previously been described elsewhere.6 Unipolar electrogram signals were stored. Local activation time was automatically calculated from unipolar electrograms by determining the maximum negative dV/dt (maximum change in voltage over time), which was later confirmed manually. Transmurally in the LV, electrograms recorded from the electrodes on the plunge needles from the distal electrode to the proximal electrode were localized to four layers of the LV myocardium. We defined these layers as being endocardial, subendocardial, subepicardial, and epicardial, respectively (distal to proximal) (Figure 1C and D.
Definitions of measurements • Epicardial measurements (Figure 1B): Global epicardial activation was calculated from the epicardial sock electrode array by averaging the mean activation times of each epicardial region of the heart. Regional epicardial activation times were derived from electrodes on the sock array representing different surface regions of the heart. • Transmural measurements (Figure 1D): LV intralayer activation times were defined as the mean of the electrogram LATs in each layer of the myocardium, as recorded by the plunge needles (e.g. summation of LATs recorded in the subepicardial layer divided by the number of subepicardial recordings). The average LV transmural activation time was taken as the mean of all four intralayer LATs (i.e. (epicardial LATs þ subepicardial LATs þ subendocardial LATs þ endocardial LATs)/4 layers). Regional LV transmural activation times were mean LATs derived from electrodes on the plunge needles representing different LV regions (anterior base, posterior base, apex, lateral free wall, mid-anterior free wall). Total LV transmural activation time was defined as the length of time between pacing and the latest activation in all transmural layers. Transmural patterns of activation, based on the plunge needles, were classified as either: (i) simultaneous (
