Optimized ventricular restraint therapy: Adjustable restraint is superior to standard restraint in an ovine model of ischemic cardiomyopathy

Abstract

Objective The effects of ventricular restraint level on left ventricular reverse remodeling are not known. We hypothesized that restraint level affects the degree of reverse remodeling and that restraint applied in an adjustable manner is superior to standard, nonadjustable restraint. Methods This study was performed in 2 parts using a model of chronic heart failure in the sheep. In part I, restraint was applied at control (0 mm Hg, n = 3), low (1.5 mm Hg, n = 3), and high (3.0 mm Hg, n = 3) levels with an adjustable and measurable ventricular restraint (AMVR) device. Restraint level was not altered throughout the 2-month treatment period. Serial restraint level measurements and transthoracic echocardiography were performed. In part II, restraint was applied with the AMVR device set at 3.0 mm Hg (n = 6) and adjusted periodically to maintain that level. This was compared with restraint applied in a standard, nonadjustable manner using a mesh wrap (n = 6). All subjects were followed up for 2 months with serial magnetic resonance imaging. Results In part I, there was greater and earlier reverse remodeling in the high restraint group. In both groups, the rate of reverse remodeling peaked and then declined as the measured restraint level decreased with progression of reverse remodeling. In part II, adjustable restraint resulted in greater reverse remodeling than standard restraint. Left ventricular end diastolic volume decreased by 12.7% (P = .005) with adjustable restraint and by 5.7% (P = .032) with standard restraint. Left ventricular ejection fraction increased by 18.9% (P = .014) and 14.4% (P<.001) with adjustable and standard restraint, respectively. Conclusions Restraint level affects the rate and degree of reverse remodeling and is an important determinant of therapy efficacy. Adjustable restraint is more effective than nonadjustable restraint in promoting reverse remodeling.

Physiological Implications of Myocardial Scar Structure

“…A similar trend is also observed with another variation of passive LV restraint: optimized and adjustable restraint. Several studies in sheep have examined the effects of a fluid-filled bladder device, which can be inflated and deflated to achieve an optimum restraint level (87, 153). In a study of optimized, static LV restraint, Ghanta and associates found that the degree of restraint decreased over time as the LV cavity reverse remodeled, to the point where there was no longer any restraint pressure being applied at the conclusion of the experiment (87).…”

“…In a study of optimized, static LV restraint, Ghanta and associates found that the degree of restraint decreased over time as the LV cavity reverse remodeled, to the point where there was no longer any restraint pressure being applied at the conclusion of the experiment (87). A follow-up study by the same group compared optimized static restraint to adjustable restraint, in which fluid was added to the balloon lumen to maintain a constant restraint pressure over the course of remodeling (153). Although adjustable restraint was more effective in limiting LV dilation, no functional improvements were observed compared to the static restraint group.…”

Injectable Microsphere Gel Progressively Improves Global Ventricular Function, Regional Contractile Strain, and Mitral Regurgitation After Myocardial Infarction

“…With a trend towards less-invasive treatment modalities, localized ventricular restraint/stiffening devices and injectable biomaterials have gained considerable clinical and research interest in the secondary prevention of heart failure [5,10,11,14,33,34]. While this study focuses on a single treatment, our group and others are actively involved in the development of other catheter-based therapeutics which are designed to alter the biochemical milieu and/or LV material properties [15–18,35,36].…”

Effect of Scar Compaction on the Therapeutic Efficacy of Anisotropic Reinforcement Following Myocardial Infarction in the Dog

“…In a study of post-MI LV restraint in sheep, Ghanta et al observed that the restraint level (selected to be optimum at the time of implantation) decreased over time as the LV reverse remodeled, to the point where there was no longer any restraint pressure being applied to the LV at the final time point [36]. In a follow-up study exploring the effects of adjustable restraint during healing, the same group explored a dynamic approach in which restraint pressure was maintained constant during healing and found enhanced reductions in LV volumes compared to static restraint [37]. Another group used a local device to examine the effects of optimized, static infarct restraint on LV remodeling and found that local reinforcement led to smaller LV volumes but no improvement in SV [38].…”