Eur J Cardiothorac Surg 2007;31:55-64. doi:10.1016/j.ejcts.2006.09.024
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
Effect of passive cardiac containment on ventricular synchrony and cardiac function in awake dogs
Isaac Georgea,1,
Yanping Chengb,1,
Geng-Hua Yib,
Kun-Lun Hec,*,
Xiaolong Lib,
Mehmet C. Oza,
Jeffrey Holmesd,
Jie Wangb,e,f,*
a Department of Surgery, Division of Cardiothoracic Surgery, Columbia University, College of Physicians and Surgeons, New York, NY, United States
b Department of Medicine, Division of Cardiology, Columbia University, College of Physicians and Surgeons, New York, NY, United States
c Department of Cardiac-Nephrology, Chinese PLA General Hospital, Beijing, PR China
d Department of Biomedical Engineering, Columbia University, New York, NY, United States
e The Jack Skirball Center for Cardiovascular Research, Orangeburg, NY, United States
f Institute of Molecular and Experimental Therapeutics, East China Normal University, Shanghai, PR China
Received 16 May 2006;
received in revised form 18 September 2006;
accepted 20 September 2006.
* Correspondence to: Kun-Lun He, Chinese PLA General Hospital, Beijing, PR China. Tel.: +86 10 6815270; fax: +86 10 68181689 or Jie Wang, Institute of Molecular and Experimental Therapeutics, East China Normal University, Shanghai, PR China. Tel.: +86 201 888 0809; fax: +86 201 541 7088. (Email: hekunlun2002{at}yahoo.com; drjiewang{at}gmail.com).
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Abstract
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Objective: Passive restraint of the left ventricle (LV) has been shown to have beneficial effects on acute hemodynamics and reverse remodeling in both animal and human models. The goals of this study were to test whether a left ventricular support device (LVSD) improves LV synchrony and/or affects cardiac performance. Methods: Ten dogs were chronically instrumented to measure hemodynamics and LV volume (sonomicrometry). Congestive heart failure (CHF) was induced by repeated intracoronary microembolization via a chronically implanted coronary catheter. The LVSD was implanted after establishment of CHF in five animals, and five animals were observed as controls. All animals were then observed for 8 weeks. A mathematical model to measure LV synchrony was used to evaluate LV motion over time. Results: Mean arterial pressure and LV pressures was significantly increased after LVSD therapy, and LV pressure–volume relationships were shifted leftwards, although no change was seen in ejection fraction, end-systolic elastance, or LV dP/dt versus control. There was no significant change in diastolic function in LVSD animals compared with control animals. End-diastolic volumes were reduced by 15% after 8 weeks with LVSD treatment, versus an increase of 8% in control animals (p
< 0.05). Synchrony was significantly improved with LVSD therapy compared with control (9% vs 76% of baseline) in 1 of 11 ventricular dimension axes (Anterior–Apex). Conclusions: LVSD therapy provided only minimal improvement in ventricular synchrony and partially improved hemodynamics. Further study into mechanisms of benefit are warranted.
Key Words: Heart failure surgery • Myocardial remodeling • Cardiac function
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1. Introduction
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Efforts to reverse left ventricular (LV) remodeling and to reduce LV wall stress in congestive heart failure (CHF) have been pursued via pharmacologic, surgical, and device approaches. Left ventricular passive support devices (LVSD) are surgically implanted to limit progressive dilatation through containment, reducing wall stress and thereby restoring normal left ventricular sphericity [1]. Several benefits of these devices have been documented, including improvements in NYHA class, lower end diastolic volume (EDV), decreased myocardial mass, and improved mitral regurgitation (MR) [2]. Reverse remodeling at a molecular level is similarly seen, with reduced cardiomyocyte hypertrophy, reduced interstitial fibrosis, and a reduced oxygen diffusion distance [3,4].
Abnormalities in wall motion are another component in declining LV function, especially in ischemic dilated cardiomyopathy. Segmental akinesis, with endocardial necrosis and transmyocardial sparing, develops after myocardial injury over time and contributes to paradoxical LV movement as well as aneurysm formation [5]. Clinically, patients with asynchronous wall motion demonstrate impaired LV filling. It is known that a LVSD reduces sphericity and qualitatively improves wall motion by echocardiography, computed tomography, and magnetic resonance imaging [2,6]. At the current time, it is unknown if LV synchrony improves after LVSD placement and if changes in synchrony affect myocardial function after prolonged duration of device support. In addition, there have been conflicting reports on the effect of LVSD therapy on systemic hemodynamics, ejection fraction, and cardiac contractile function. Accordingly, the objectives of the present study were to evaluate the effect of passive ventricular restraint using the Paracor® LVSD on LV synchrony, LV remodeling, and systolic and diastolic function after implantation of the novel left ventricular passive support device using chronically instrumented dogs with coronary embolization induced-CHF in an awake state.
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2. Materials and methods
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2.1 Study design
A daily coronary-embolization (Embo) model, which has been well established for inducing stable but severe systolic and diastolic dysfunction [4,7–10], was used in 10 mongrel dogs to create CHF. After a stable CHF was established by daily Embo, a thoracotomy was performed, and an LVSD was implanted in five treatment animals. The remaining five animals underwent a sham thoracotomy and were observed during the same time period without receiving device implantation, serving as a control group. At the end of 8 weeks after device implantation or observation, the experiment was terminated in both treatment and control groups. This study was approved by the institutional Animal Care and Use Committee of Columbia University, which conforms to the ‘Guide for Care and Use of Laboratory Animals’ published by the National Institutes of Health (NIH publication 86 to 23, 1985).
2.2 Surgical preparation
On the day of each surgery, each animal (22–25 kg) was premedicated with Telazol 3–5 mg/kg i.m. and induced with thiopental 15–20 mg/kg i.v. The animal was then intubated and maintained under anesthesia using isoflurane at 1.5–2.5% on mechanical ventilation. A left thoracotomy was performed between the 4th and 5th intercostal space to expose the heart. A Konigsberg solid-state pressure gauge (6.5, Konigsberg Instruments Inc., Pasadena, CA) was placed through the LV apex to measure LV pressure. Fluid filled catheters were placed in the ascending aorta and the LV to measure aortic pressure and calibrate the Konigsberg pressure gauge, respectively. A pneumatic cuff was placed around the inferior vena cava (IVC) to vary loading conditions post-operatively. The left anterior descending coronary artery (LAD) was isolated, and a thin silastic cannula was inserted through an arteriotomy for Embo administration. In addition, six sonomicrometric crystals (1.5 mm x 1.5 mm, Sonometrics Corp., London, Canada) were placed in the anterior LV (Ant), septum (Sept), base, posterior LV (Post), LV free wall (Free), and LV apex. All catheters, cables, and wires were tunneled to the back of the dog subcutaneously and housed in a specially designed backpack. The animal was allowed to recover from the surgery and trained to lie on an experimental table quietly for data acquisition in an awake state.
2.3 Coronary embolization-induced heart failure
This model has been described previously in detail [4,7–10]. In brief, CHF was produced by daily intracoronary microembolization with 25,000–50,000 (90–120 µm in diameter) polymer bead injections through the previously implanted LAD cannula. Embolization proceeded until LVEDP reached 15 mmHg and LV dP/dt was less than 2400 mmHg/s. Embolization was halted at this time, and hemodynamics and echocardiography were repeated in an awake state after an additional 5–7 days to confirm the stability of the CHF state. The daily coronary microembolization results in a multifocal pattern of scarring and large scattered areas of fibrosis and granulomas surrounding large clusters of microbeads in the LV myocardium [4]. The reproducibility and stability of this CHF model have been demonstrated by our group and other investigators [4,7–10].
2.4 Left ventricular support device placement
The Paracor® device (Paracor Medical Inc., Sunnyvale, CA) is made of nitinol and has a first order relationship between ventricular load (pressure) and stretch (compliance) [11]. A second surgery was performed to place the Paracor® device in five animals. Animals were again anesthetized, intubated, and mechanically ventilated. A left thoracotomy was performed in the 4th and 5th intercostal space, and adhesions removed to expose the surface of the heart. Device size selection was based on an intra-operative physical measurement of the (1) ventricular circumference at the level of the mitral annulus and (2) length from base to apex in order to ensure a snug fit with minimal tension on the heart. A suture was secured to the apex and threaded through the bore of the delivery system. Using this suture as an anchor, the device was slid over the right, left ventricle, and Konigsberg catheter, and placed in the appropriate position (see Fig. 1
). After placement, approximately 75% of the ventricular surface area was enclosed by the device, with the LV apex and both atria uncovered. The anterior wall (area of myocardial injury) was covered completely by the device. Implant delivery was successful and the desired fit was achieved in all five animals. The animals recovered in approximately 7–10 days from the surgery.
2.5 Hemodynamics and echocardiography
Hemodynamics and echocardiography were measured as previously described [10] at baseline, CHF state, 4 weeks, and 8 weeks after device implantation. Arterial pressure and LV systolic pressure (LVSP) were measured by attaching the previously implanted catheters to P23ID strain-gauge transducers (Statham Instruments, Inc., Oxnard, CA). Mean arterial pressure (MAP) was determined on-line by use of 3 Hz averaging filters (DA26, Medtron Engineering, Olivenhain, CA). Data was recorded on an eight-channel thermal writing chart recorder (30-V8808-10, Gould Electronics, East Rutherford, NJ), and periods of interest were digitized (Gateway 2000 486 computer equipped with a National Instruments analog-to-digital conversion system) for off-line analysis. Mitral valve function was assessed at mid-systole in LVSD animals using a Hewlett-Packard Sonos 5500 machine from 2- and 4-chamber images.
2.6 Pressure–volume loop analysis
LV pressure and LV volume were measured at baseline, CHF state, 4 weeks, and 8 weeks after device implantation via previously implanted solid state pressure gauges in the LV and sonomicrometric crystals in an awake state. Briefly, LV pressure–volume (PV) relationship loops were measured at rest and during a transient preload reduction induced by IVC occlusion. LV volumes (LVvol) and ejection fraction (EF) were estimated from sonomicrometrically measured dimensions assuming a 3-axis ellipsoid model: LVvol
=
AP·SF·AB/6, where AP is anterior–posterior, SF is septal-free wall, and AB is apex–base dimensions. End-systolic and end-diastolic pressure and volume data points from individual PV loops were obtained using custom software (Matlab, v. 6.5). Using the end-systolic pressure and volume data points, the end-systolic PV relationship (ESPVR) was assessed using a linear regression to the equation: E
es
=
P
es/(V
es
–
V
0), where the slope (end-systolic elastance, E
es) defines contractility, and V
0 its volume-axis intercept. In order to avoid the non-linearity bias of the V
0 intercept at non-physiologic ranges, the V
70 intercept (LV volume at 70 mmHg) was also calculated and reported. The end-diastolic PV relationship (EDPVR) was determined by applying non-linear regression analysis to the end-diastolic pressure and volume points (P
ed and V
ed, respectively). These data were fit to the following equation: 
, where 
is the chamber stiffness constant, and ß is a scaling constant. Each measurement was calculated and averaged over 10 cardiac cycles. This method of determining ESPVR and EDPVR was repeated for each animal and each measurement time point. Arterial elastance, Ea, was calculated as stroke volume/end-systolic pressure. All calculations were made using custom software (Matlab, v. 6.5) and have been used previously [10].
2.7 Preload-recruitable systolic reserve
Because the LVSD imposed an external containment around the heart, one concern was that the observed reverse remodeling would be accompanied by inhibition of cardiac preload reserve. Rapid administration of 1000 ml of saline 8 weeks after device implantation was used to test diastolic constriction in three animals.
2.8 Assessment of synchrony
Previously implanted sonomicrometric crystals were used to assess synchrony. Segment length was recorded at the time of hemodynamic recordings in an awake state during steady state at baseline, at the CHF state, after 4 weeks, and 8 weeks after device placement or observation. Synchrony was quantified by calculating the relative time (SyncT) in one cardiac cycle to reach minimum segment length, measured from end-diastole:
 | (1) |
where t
min is time at minimum segment length, t
ED-1 is time at end-diastole, and t
ED-2 is the time at the subsequent end-diastole in the cardiac cycle. This index, SyncT, provides a measure at which point in the cardiac cycle maximal contraction is occurring. The magnitude of this segment length difference at minimum segment length (SyncL), or amplitude, is calculated relative to the length at end-diastole as:
 | (2) |
where L
min is the minimal segment length and L
ED-1 is the segment length at end-diastole. These two definitions of synchrony provide measures of both temporal and spatial changes in LV wall motion normalized to one cardiac cycle. The above analysis was performed for the following segment pairs for both treatment and control animals: (1) Free–Apex, (2) Ant–Sept, (3) Ant–Free, (4) Ant–Post, (5) Apex–Base, (6) Sept–Free, (7) Apex–Sept, (8) Ant–Base, (9) Post–Base, (10) Post–Apex, and (11) Ant–Apex. Each measurement was calculated and averaged over 10 cardiac cycles. All calculations were performed using custom software (Matlab, v. 6.5).
2.9 Statistics
Values are reported as mean ± standard error. A Student's t-test was used for subgroup comparisons made between measurements obtained at baseline, CHF state, and after device implantation. Significance was adjusted for multiple comparison where appropriate using one-way ANOVA with post-hoc Bonferroni analysis. Analysis was performed using SPSS v. 11.5 (Chicago, IL).
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3. Results
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3.1 Hemodynamics and echocardiography
One animal died after 4 weeks of LVSD treatment due to a surgical site infection and was not included in any portion of the analysis. There was no morbidity or mortality associated with device implantation, catheter implantation or use, or surgical preparation. There were no significant epicardial adhesions noted at the time of heart removal at experiment termination in LVSD animals. Table 1
provides a summary of the hemodynamic data. After 6.0 ± 1.5 weeks of coronary microembolization, all animals developed a stable heart failure.
Animals had a sustained increase in MAP and LVSP up to 8 weeks after LVSD placement versus control animals (p
< 0.05). LV dP/dt was significantly reduced by coronary embolization in both control and LVSD groups at CHF. There was no significant difference in LV dP/dt after 8 weeks.
The LVSD proved effective in reducing in LV volumes after induction of CHF, as shown in Fig. 2
. Embolization produced an increase in EDV in all animals, which was not statistically different between LVSD and control groups. After 8 weeks, EDV was significantly reduced by 15.5 ± 7.1% in animals with LVSD therapy compared to an increase of 8.1 ± 21.1% in control animals (p
< 0.05). Ejection fraction (EF) after 8 weeks of LVSD treatment was not significantly different from the control group (Table 1).
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Fig. 2. Left ventricular end-systolic volume (ESV) and end-diastolic volume (EDV) after left ventricular support device therapy (LVSD). CHF, congestive heart failure.
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Mitral regurgitation (MR) was present in one out of five LVSD treated animals at CHF, and LVSD therapy did not affect the grade of MR in this animal, as shown in Table 2
. There were no significant differences in mitral valve annular area, annular dimensions, or papillary muscle dimensions at mid-systole (Table 2).
3.2 Pressure–volume loop analysis
The results of PV loop analysis at steady state and during IVC occlusion are summarized in Table 3
and Fig. 3
. LV remodeling was apparent after embolization at CHF, as evidenced by the rightward shift of the PV loops. LV remodeling was sustained in control animals without the LVSD therapy (Fig. 3, Panel A) but was partially reversed by LVSD treatment, as demonstrated by the leftward shifting of the PV loops at 4 weeks with some rightward regression apparent at 8 weeks (Fig. 3, Panel B). Covariance analysis of ESPVR also demonstrated a similar trend (not shown). End-systolic elastance (E
es) trended towards reduction after 8 weeks of LVSD therapy compared to control (p
= 0.06). Chamber stiffness () increased significantly with coronary embolization, as expected, and a trend to reduction was seen after 8 weeks of LVSD therapy versus control (p
= 0.18). Despite equal values at baseline, a trend towards increased isovolemic relaxation (
) was seen at CHF and 4 weeks in LVSD; by 8 weeks, was slightly lower with LVSD therapy than control (p
= 0.09).
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Fig. 3. Representative pressure–volume (PV) loops at steady state (A, C) and inferior vena cava (B, D) occlusion. LVSD-left ventricular support device.
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3.3 Preload-recruitable reserve
As shown in Fig. 4
, saline infusion (i.e., increased preload) appropriately increased LVSP, LVEDP, MAP, and LV dP/dt, accompanied by rightward and upward shifted PV loops. The absence of a restrictive pattern indicated LV diastolic constriction was not present after device implantation.
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Fig. 4. Cardiac preload reserve. To test preload reserve, saline was rapidly infused in three left ventricular support device animals.
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3.4 Left ventricular synchrony
Synchrony was assessed by examining both the relative point in the cardiac cycle at which minimal crystal segment length (SyncT) occurred and the magnitude of segment length at that point (SyncL). Dyssynchrony, as defined by derangement of SyncT and SyncL relative to baseline, was evident in all 11 ventricular dimensions at CHF, with no significant differences between LVSD and control in any dimension (See Fig. 5A and B). Dyssynchrony in SyncT persisted equally for 8 weeks in both LVSD treated and control animals in all dimensions except Ant–Apex and Apex–Sept. In the Ant–Apex dimension, SyncT was improved to 9.1 ± 5.3% of baseline in animals with LVSD placement compared to 76.1 ± 12.0% of baseline in control animals (p
< 0.005) (Fig. 5C). A trend to improvement was also seen in SyncT in the Apex–Sept dimension in animals with LVSD therapy (p
= 0.089 vs Control) (Fig. 5D). There were no changes in SyncL in any dimension after LVSD placement compared with control.
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Fig. 5. SyncT and SyncL for control and left ventricular support device (LVSD) animals. SyncT or the time to minimum segment length within one heart beat, is graphically displayed as occurring at a percentage of one cardiac cycle in (A) control and (B) LVSD animals. SyncL or the difference between end-diastolic segment length and minimum segment length is graphically displayed as a percentage of end-diastolic segment length in (A) control and (B) LVSD animals. A significant improvement towards baseline in the time during the cardiac cycle at which minimal segment length occurs (SyncT) was seen after 8 weeks in the Anterior–Apex dimension with the LVSD compared with control (C). A trend to improvement in SyncT was also seen in the Apex-Septal wall dimension (D). CHF, congestive heart failure.
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4. Discussion
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Surgical options for advanced heart failure, consisting of transplantation or assist device placement, are maximally invasive, risky, and financially expensive. The concept of surgical LV reconstruction and reshaping, popularized by Batista et al. [12], Doret al. [13], and others, aim to restore normal LV geometry and reduce ventricular wall stress, but long-term clinical benefits have not been demonstrated. More recently, LV passive support devices have been introduced to limit ventricular dilatation. Results from preliminary animal experiments and clinical studies suggest that ventricular containment may provide long-term reverse remodeling by preventing late dilatation [1–4,11,14]. In the current study, heart failure was induced in 10 animals through coronary microembolization. An LVSD was then surgically implanted, and the animals were monitored for 8 weeks. Systemic hemodynamics, echocardiography, and LV pressure-volume relationships were assessed in an awake state. A mathematical method to assess ventricular synchrony was used to quantitate wall motion. The primary findings of this study were that (1) LV remodeling was partially reversed by LVSD treatment, (2) contractile function was partially improved after 8 weeks of LVSD treatment, and (3) the LVSD did not significantly improve LV synchrony after CHF. Although the LVSD achieved the goal of limiting dilatation, reducing ventricular volumes, and partially improving hemodynamics, these benefits did not fully translate into improved ejection fraction. We have demonstrated that ventricular synchrony is quantitatively deranged with CHF and progressively worsens with time. The placement of an LVSD did not correct ventricular dyssynchrony after heart failure.
The mechanisms responsible for the benefits of an LVSD have been partially shown previously [1–4,6]. First, by restraining the ventricular radius and limiting wall thickness, the device decreases wall stress and likely myocardial consumption as well. Second, MR has also been shown to be decreased by echocardiography with an LVSD [6]. The third contribution is its effect on wall motion. As noted by prior investigators, significant akinesis or dyskinesis of the ventricular wall greatly affects filling [6]. Thinned myocardium is theorized to become akinetic or dyskinetic as infarction size expands over time [6]. We hypothesized that the LVSD would not only contain this expansion but also return ventricular contraction to its baseline state, which intuitively is most efficient. The synchrony model used measures both the relative time in the cardiac cycle at which maximal shortening occurs and the amplitude at that point, providing a precise and quantitative representation of ventricular synchrony based on 11 dimensional axes. Synchrony was found to change in all dimensions, not just in axes involving the area of ischemia as previously thought, and changed tremendously in some cases, highlighting its importance in the progression of heart failure. The LVSD, with the exception of the Anterior–Apex dimension, did not change dyssynchrony, even after 8 weeks of therapy and despite achieving its therapeutic goal of limiting ventricular dilatation. Previous studies have shown that sphericity, a physical geometric property representing the curvature of the ventricle, is reduced after LVSD; reduction in sphericity is theorized to decrease wall stress and myocardial consumption [15]. Lembcke et al. [15] reported improved wall motion and reduced areas of akinesis and hypokinesis in 8 human subjects after LVSD. However, these indices are distinct from synchrony and do not reflect the principle measured in this study. The improvement in regional wall motion and reduction of akinetic segments, shown also by Pilla et al. [6], are important benefits provided by an LVSD but may not change synchrony, as shown in the current study. Scar formation after myocardial infarction can be extensive enough to create ‘systolic bulge,’ and these segments subsequently move paradoxically [16]. This paradoxical motion impairs function, steals stroke volume, and reduces systolic function [17]. Remote myocardium compensates for loss of functional myocardium, worsening wall motion abnormalities and dyssynchrony. With the placement of an LVSD alone, in which scar and akinetic/dyskinetic myocardium are left in place, it is unlikely that synchrony can be changed based solely on reduction of akinetic segments or improvements in regional wall motion. Surgical procedures to reduce abnormally contractile areas (ischemic or non-ischemic) by eliminating akinetic and dyskinetic areas, such as in the endoventricular circular patch plasty (EVCPP), or Dor procedure, have been shown in humans to acutely enhance cardiac function and restore normal global myocardial contractile synchrony and forces [18–20]. A surgical procedure, such as EVCPP to excise abnormally contracting areas, may restore synchrony, and the additional placement of an LVSD may prevent late failure associated with EVCPP [18] by limiting ventricular dilatation. Ventricular reduction plus containment has not been attempted to date, to our knowledge, but it is an intuitive combination given the limitations of the two existing technologies. Further study will be necessary to determine if this approach is technically feasible and clinically effective.
This study also presents important data concerning systolic function after LVSD placement. Discrepancies in the effect of LVSD therapy on cardiac function exist in the literature. In two studies by Lembcke et al. [2], ACORN placement in 14 patients increased EF from 20% to 28% and produced a higher EF by computed tomography in 9 patients [15]. Similarly, EF was improved from 19% to 30% in sheep with severe heart failure after ACORN placement after one month. In that study, cardiac output and LV dP/dt also increased dramatically, accompanied by a reduction in wall stress by over 33% [21]. Sabbah et al. [3] also demonstrated higher ejection fractions after ACORN placement in animals. However, EF was not significantly different in the randomized ACORN-CSD clinical trial with an enrollment of 300 patients [22]. Additionally, no change in EF was seen in a canine ischemic heart failure model by Saveedra et al. [4] after ACORN placement. Cardiac output has consistently been shown to be unchanged after LVSD therapy [2,4]. Our study supports the latter findings, as EF did not change. Systolic function, as measured by the load and heart rate independent index E
es and LV dP/dt, was not significantly changed; however, LV pressure–volume relationships were leftward shifted while MAP and LVSP were significantly increased in the LVSD treatment animals after 8 weeks, indicating that contractile function was partially improved. Another finding that deserves mention was that diastolic function, as assessed by isovolemic relaxation (), chamber stiffness, and LVEDP, was not adversely affected by passive ventricular containment. Rapid volume loading with saline confirmed adequate preload reserve. The absence of restrictive physiology has been demonstrated by our rapid volume loading experiments, which is consistent with other studies [4]. However, the importance of preload reserve in this setting has yet to be determined. Absence of restrictive physiology in response to volume loading may be detrimental in the long-term, as exercise-induced dilatation may occur periodically. This intermittent dilatation has been suggested to be an important factor in continued remodeling in heart failure and late LVSD failure, and requires further research in clinical study. Finally, the present study and other studies [4,6] present convincing evidence for LVSD use after acute myocardial infarction to prevent further remodeling, as well as decrease ventricular dilatation in chronic dilated cardiomyopathy.
The Paracor device offers a number of attractive features over the current LV passive support devices available that may expand its usage. The minimally invasive approach, although not used in this experiment, will undoubtedly allow patients too sick to undergo a median sternotomy to receive the device. The technical ease to place the device versus other devices is a second concern that makes the Paracor attractive. The small amount of force generated on the myocardium by the nitinol Paracor device (1–3 mmHg) [11], as opposed to none for other devices, may prove to support the heart to a greater degree later in the course of treatment. The compliance features of each device have generated much discussion. Other devices claim a lower circumferential compliance than longitudinal compliance, possibly forcing the heart into an ellipsoid shape. In practice, it remains to be seen whether this feature is compromised after fitting and chronic use, which would eventually cause longitudinal shortening secondary to late dilation. These unfavorable characteristics are avoided in the design of the Paracor device, which does not shorten when stretched circumferentially. Further clinical studies addressing safety and feasibility are currently beginning and should resolve some of these concerns.
The limitations of this study include those inherent to animal studies. First, the small sample size of this study necessitates a larger clinical study to confirm the results presented here. Second, although control animals appeared to suffer equivalent myocardial injury after coronary embolization as treatment animals based systemic hemodynamics, the degree of injury may have been less than that of treated animals. This is reflected in decreases in E
es in control animals, which did not decrease as severely as in LVSD treated animals. Third, the length of this study is sufficiently short to possibly miss the effects of synchrony and contractile function improvements after LVSD; for example, it is known that time to akinesia or dyskinesia can take up to 3 years [16] to develop after infarction, and recovery may take as long as well. Finally, molecular and biochemical markers of reverse remodeling were not measured and, thus, we are unable to correlate our functional findings.
Despite its limitations, the current study presents data that an LVSD partially improves hemodynamics, effectively limits dilatation, and reversed remodeling of the ventricle; however, LVSD therapy has minimal effects on LV synchrony. As more data confirms the positive effects of an LVSD on reverse remodeling, a less invasive approach of placement may expand its use in the heart failure and acute myocardial infarction populations.
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Acknowledgments
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We would like to thank Yuankai Tao, Siyi Qin, Kenward Yu, Jordan Muraskin, and Ilan Hay for their technical assistance throughout this project. This work was supported by a research grant to Dr Jie Wang from Paracor Medical, Inc. Dr Jie Wang is partially supported by a grant (IRT0430) from The Ministry of Education, PR China.This work was partially supported by National Institute of Health Grant T32-HL07854 (I.G.). Dr Mehmet Oz has received laboratory research support from Acorn Cardiovascular Inc. in the past.
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Footnotes
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1 These authors contributed equally to this manuscript. 
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Abstract
1. Introduction
