The never-ending uphill slope: assessing paced ventricular function in the era of advanced mechanical imaging

This editorial refers to ‘Left ventricular apical pacing in children: feasibility and long-term effect on ventricular function’, by J. Kovanda et al., on pages 306--313. The seemingly simple contraction of the heart is anything but, involving not only elements of narrowing, shortening, lengthening, and widening, but also their resultant twisting or wringing motions.1 The complex ultrastructure of cardiac myofibres—involving a subepicardial clockwise helix and an opposing subendocardial counterclockwise helix—has been known for over 300 years. However, our ability to readily observe, measure, and assess these motions, both individually and in the aggregate, has greatly advanced over the last two decades. The evolution of modern non-invasive imaging technology has provided deeper insight into this fundamental question of how the heart moves and squeezes. Qualitative and quantitative assessment of ventricular function by two-dimensional echocardiography has been further augmented by tissue Doppler imaging (TDI), allowing for a more nuanced assessment of myocardial velocities throughout the cardiac cycle and more detail specifically about diastolic function. Mathematical derivations applied to TDI allow for the determination of strain and strain rate, giving information about local deformation. This became easier to implement—and for the non-echocardiographer to make sense of—with the advent of speckle-tracking echocardiography (STE), which provides a clear visual representation of both regional and global myocardial deformation. The colour depiction of STE is to the echocardiographer what three-dimensional electroanatomic mapping images are to the electrophysiologist. Both of these technologies have brought images collected and integrated in our brains onto the screens for visual display and improved understanding of the relationship of timing in the heart. While the literature is filled with various applications of these tools to assess the ‘what’ and ‘how’ of cardiac function, it is the ‘when’ that can bring the echocardiographer and the electrophysiologist together. Advanced mechanical imaging provides a visual bridge with which to observe the effects of conduction abnormalities, and this can be invaluable for patients with arrhythmias and conduction abnormalities, and particularly for those requiring pacemaker therapy. Not only can we see what moves, measure how much it changes, and determine how rapidly that occurs, but we can also assess when these events occur with the temporal resolution of a few milliseconds along with spatial relationships. These methods are commonly used to help determine who will optimally respond to cardiac resynchronization therapy (CRT) beyond typical electrocardiographic characteristics. Various combinations of traditional and advanced imaging modalities can be used both to determine who might benefit from biventricular pacing and if so, how to optimize the timing of left and right ventricular activation.2 These techniques require varying degrees of expertise, effort, and time. Predicting responders to CRT in paediatrics and congenital heart disease is still an area of intense investigation. However, left ventricular (LV) dysfunction from chronic right ventricular (RV) pacing is a well-recognized problem3,4 and other potential solutions to avoid the associated deleterious remodelling5 that accompanies it certainly merit investigation. The article in this issue of Europace by Kovanda et al.6 reports on patients with complete atrioventricular block with and without congenital heart disease who underwent LV apical pacing. This cross-sectional study evaluated young patients (mean age 7 years at evaluation, ranging from 3 to 10 years; mean age at pacemaker implantation 1 year, range 0–5 years) who were paced from the LV apex long-term (mean duration, 3.9 years). The authors evaluated laboratory and exercise data along with traditional echocardiographic measures of ventricular size and function, Doppler-based assessments of interventricular synchrony, and detailed STE measurements of global and regional function and their timings. Their key findings were that children undergoing LV apical pacing had decreased maximal heart rates and maximal oxygen consumption during exercise testing but preserved LV function as measured by shortening fraction, ejection fraction, and global longitudinal strain. Importantly, while there was an increase in the apical to basal mechanical delay, there was no difference in interventricular delay, opposing LV wall motion delay or efficiency of work as measured by post-systolic contraction (an inefficient manifestation of cardiac deformation). The authors did note evidence of inefficiency as measured by higher systolic internal stretch, which correlated with the apical to basal mechanical delay. The authors conclude that the associated contraction inefficiency was well tolerated given the normal ejection fraction, shortening fraction, and global longitudinal strain. They hypothesize that the heart can adapt to a certain degree of inefficiency and that an apical-to-basal mechanical delay may be better tolerated than the septal to lateral delay classically associated with RV pacing and the subsequent development of cardiomyopathy. The authors undertook a rigorous evaluation of LV mechanics in addition to assessing RV–LV timing in order to assess a truly three-dimensional model of dyssynchrony. This is an important methodological approach when the main question being addressed is the selection of the optimal pacing site, as the classic septal–lateral delay may not be expected in the absence of RV pacing (or a left bundle branch block). Their investigation went even further than assessing the relative timing of myocardial contraction, and they should be applauded for addressing the fact that not all contraction is equal, as contraction efficiency is influenced by when and where it occurs. Results here were mixed: while there was no change in post-systolic shortening, there was inefficiency systolic stretching. The authors’ proposal that this is well tolerated may be true; however, with a mean duration of follow-up of 4 years, it is difficult to say for certain. Pacemaker-induced cardiomyopathy can present after more than a decade of preserved function with chronic RV pacing.3 While the relatively small number of patients and follow-up interval here are important caveats, the medium-term results including exercise testing, ventricular size, preservation of intraventricular synchrony, and normal global function are promising. The observed apical-to-basal delay is not surprising as activation propagates from the LV lead outward. However, this may have important consequences despite the preserved global functional measurements. The authors noted an increased in the LV end-diastolic diameter with LV apical pacing despite an unchanged end-diastolic volume. This suggests altered ventricular geometry, which did not appear to affect function during the study period. However, combined with early apical activation, it may have important implications for the efficiency of blood ejection beyond measurements of deformation efficiency. The importance of the ‘wringing’ motion of the left ventricle is well established, with most twisting occurring at the apex. The oblique nature of apical myofibres allows 15% shortening to result in 60% ejection; with a transverse orientation that occurs at the base, the same shortening yields only 30% ejection.1 This complex movement contributes to the formation of intraventricular vortices, which can now be studied using ultrasound based, non-invasive particle image velocimetry. Unsurprisingly, conduction abnormalities (including those from pacing) disrupt these vortices and disturb the transfer of kinetic energy during the cardiac cycle.7 One might consider that the limited maximal oxygen consumption seen in paced patients in this study may not be due solely to an impaired chronotropic response, but potentially to impaired ejection. This warrants further investigation, particularly in congenital heart disease, which complicates the understanding of the mechano-electrical relationships. CRT has been shown to improve LV fluid dynamics,8 although the direct relationship of optimal vortex formation to clinical outcomes such as exercise performance and patient symptoms is less clear, especially in children. As our understanding of ventricular mechanics—and now intraventricular fluid dynamics!—improves, it becomes more challenging to know what the best endpoint is—a Sisyphean task of electromechanical evaluation. The importance of paediatric-specific studies such as this one on the effects of pacing cannot be understated. Although the congenital heart disease group in this study was small, its inclusion is important as this is a growing patient population requiring chronic pacing therapy. While CRT has been utilized in paediatrics with success,9,10 typical adult parameters may not always apply.11 Mechanical dyssynchrony in children is more heterogeneous than it is in adults, with the congenital heart disease population adding complexity by virtue of non-contractile patches, surgical scarring, systemic right ventricles, univentricular circulations, or other mechanical alterations in addition to conduction system abnormalities. And of course, children who require pacing will do so for decades longer than adult patients, which makes long-term longitudinal follow-up critical. Consideration of alternatives to right ventricular or conventional biventricular pacing is important in this diverse population. The ultimate goal for these patients is to maintain normal ventricular performance and exercise capacity over the long-term. One might argue that all of these evolving imaging techniques are missing the larger point, and the marriage of the electrophysiologist and the echocardiographer might best be improved by adding an exercise physiologist into the mix to help assess not only cardiac performance, but patient performance in a dynamic fashion. An assessment that includes necessary augmentation of cardiac output—or the inability to do so—is an equal or perhaps better endpoint. Until then, we can continue pushing the boulder up the hill. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of Europace or of the European Society of Cardiology.