Ventricular Preexcitation Modulates Strain and Attenuates Cardiac Remodeling in a Swine Model of Myocardial Infarction

Abstract

Background-Myocardial infarction modifies the distribution of stress within the heart, increasing wall stress in ischemic and surrounding tissue, which often leads to adverse left ventricular remodeling. Electrical preexcitation pacing with appropriate timing of high-stress regions can reduce local strain and may attenuate global remodeling. Methods and Results-Myocardial infarction was induced in 24 swine to study the short-term (nϭ12) and long-term (nϭ12) effects of therapy. Sonomicrometry and hemodynamic measurements were used to show the mechanistic effects of preexcitation and to determine the optimal stimulation site and atrioventricular delay. Lagrangian strain was used to assess regional loading characteristics. Long-term study animals were randomized to 8 weeks of preexcitation (therapy) or no pacing (control). Echocardiograms were performed 2 days after myocardial infarction and repeated at 60 days, when tissue weights and apoptosis were assessed. Preexcitation reduced regional strain in the short term, with the best results achieved when the border region was paced at an atrioventricular delay of 50% of the intrinsic PR interval. In the long term, the changes in left ventricular internal diameter and left atrial size were decreased in therapy animals versus control animals (0.9Ϯ0.3 versus 1.5Ϯ0.5 cm, Pϭ0.03, and 1.06Ϯ0.78 versus 2.32Ϯ0.88 cm, PϽ0.04, respectively). Heart weight was significantly lower in the therapy animals than in the control animals (319.8Ϯ20.8 versus 359.6Ϯ29.3 g, Pϭ0.02). Although not significant, cardiomyocyte apoptosis trended lower in the therapy group. Conclusions-Preexcitation of the left ventricle after myocardial infarction reduced strain and stroke work in the infarct and border regions in the short term and attenuated adverse ventricular remodeling in the long term.

Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity

“…However, at A-V delays of 50% or greater of the P-R interval, stroke work and cardiac output were similar to values without early electrical activation. Consistent with the findings of Shuros et al (18), cardiac output and developed LV pressures at the A-V delay used in the present study were not altered during the period of early electrical activation. A potential explanation of this finding is that with A-V delays that are close to the intrinsic P-R interval, the spread of depolarization in the region of myocardium that is activated early is relatively small and that LV pressure development is driven by depolarization of the LV through the normal HisPurkinje system.…”

“…In the present study, the A-V delay for the early activation LV site was set at 80 ms, which was ϳ75% of the intrinsic P-R delay when the atria were stimulated at a rate of 150 beats/min. Shuros et al (18), in the context of inducing early electrical activation of the border region of a myocardial infarct (MI), demonstrated that the reduction in regional strain with early electrical activation was inversely related to the A-V delay relative to the intrinsic P-R interval. Specifically, at an A-V delay of 10% of the intrinsic P-R interval, Shuros et al (18) observed a significant reduction in the shortening (i.e., strain) in the early activation region.…”

“…Shuros et al (18), in the context of inducing early electrical activation of the border region of a myocardial infarct (MI), demonstrated that the reduction in regional strain with early electrical activation was inversely related to the A-V delay relative to the intrinsic P-R interval. Specifically, at an A-V delay of 10% of the intrinsic P-R interval, Shuros et al (18) observed a significant reduction in the shortening (i.e., strain) in the early activation region. At longer A-V delays (25%, 50%, and 75% of the P-R interval), the attenuation of segmental shortening in the early activation region was progressively reduced.…”

“…There is an emerging interest in using electrical stimulation of the myocardium as a means to attenuate and/or prevent adverse LV remodeling after MI (4,5,18). For example, in a clinically relevant porcine MI model, Shuros et al (18) demonstrated that early electrical activation of the border region attenuated the increase in LV dimensions 8 wk after MI induction.…”

Feasibility of Biventricular Pacing in Patients With Recent Myocardial Infarction: Impact on Ventricular Remodeling

“…Whether this AV delay provides maximum benefit is unknown; however, preliminary animal studies suggest that pacing continuously at an AV delay of 60% to 75% from sites near the infarcted region is effective in attenuating adverse ventricular remodeling. 21 The optimal timing of initiating biventricular therapy following an MI has not been established and will likely have an impact on outcomes.…”