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Effect of passive cardiac containment on ventricular synchrony and cardiac function in awake dogs
Abstract
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.
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.
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).
LVSD therapy provided only minimal improvement in ventricular synchrony and partially improved hemodynamics. Further study into mechanisms of benefit are warranted.
... The HeartNet Implant provides resistance to circumferential dilation via transmural myocardial pressure. (5)(6)(7) In the context of DCM, a shift in the volume to wall thickness ratio occurs, whereby changes in epicardial pressure may directly affect intrinsic myocardial resistance to blood flow. These changes in pressure may be of particular relevance considering the HeartNet Implant may exert additive transmural compressive forces during diastole, the peak of myocardial blood flow delivery. ...
... Several cardiac support devices have been developed with the goal of attenuating the progression of DCM.(1)(2)(3)(4)(5)(6)(7)(21)(22)(23) The CorCap Cardiac Support Device (Acorn Cardiovascular, Inc, St. Paul, MN) has been examined in several experimental models of heart failure and has advanced to clinical trials, demonstrating sustained reduction in LV end diastolic and systolic volumes compared to controls.(1) ...
The present study examined a cardiac passive restraint device which applies epicardial pressure (HeartNet Implant; Paracor Medical, Inc, Sunnyvale, Calif) in a clinically relevant model of dilated cardiomyopathy to determine effects on hemodynamic and myocardial blood flow patterns.
Dilated cardiomyopatht was established in 10 pigs (3 weeks of atrial pacing, 240 beats/min). Hemodynamic parameters and regional left ventricular blood flow were measured under baseline conditions and after acute placement of the HeartNet Implant. Measurements were repeated after adenosine infusion, allowing maximal coronary vasodilation and coronary flow reserve to be determined.
Left ventricular dilation and systolic dysfunction occurred relative to baseline as measured by echocardiography. Left ventricular end-diastolic dimension increased and left ventricular fractional shortening decreased (3.8 ± 0.1 vs 6.1 ± 0.2 cm and 31.6% ± 0.5% vs 16.2% ± 2.1%, both P < .05, respectively), consistent with the dilated cardiomyopathy phenotype. The HeartNet Implant was successfully deployed without arrhythmias and a computed median mid-left ventricular epicardial pressure of 1.4 mm Hg was applied by the HeartNet Implant throughout the cardiac cycle. Acute HeartNet placement did not adversely affect steady state hemodynamics. With the HeartNet Implant in place, coronary reserve was significantly blunted.
In a large animal model of dilated cardiomyopathy, the cardiac passive restraint device did not appear to adversely affect basal resting myocardial blood flow. However, after acute HeartNet Implant placement, left ventricular maximal coronary reserve was blunted. These unique results suggest that cardiac passive restraint devices that apply epicardial transmural pressure can alter myocardial blood flow patterns in a model of dilated cardiomyopathy. Whether this blunting of coronary reserve holds clinical relevance with chronic passive restraint device placement remains unestablished.
... Increasing the tension between the two epicardial pads reshapes the enlarged LV, creating a bilobular ventricle with decreased chamber radius (174). As detailed in a recent review (46), a consistent theme emerges among studies of biventricular or LV restraint devices: global post-MI restraint reduces LV cavity size and decreases the severity of dilation but fails to generate definitive improvements in LV function (20,21,42,85,98,166,174,209,212). A similar trend is also observed with another variation of passive LV restraint: optimized and adjustable restraint. ...
Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure, and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following a myocardial infarction, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction. © 2015 American Physiological Society. Compr Physiol 5:1877-1909, 2015.
Myocardial infarction occurs when blood supply to a region of the myocardium is interrupted or eliminated, leading within seconds to loss of active contraction in the affected region and within minutes to cardiomyocyte death. Unable to contract, the infarct stretches passively each time the heart generates pressure, creating an immediate mechanical disadvantage and, if the infarct is large, triggering a cascade of pathological ventricular remodeling that eventually leads to heart failure. Therefore, a variety of therapies have been explored to mechanically reinforce the infarcted heart in the hopes of improving cardiac function and limiting adverse remodeling. This chapter will discuss two major strategies for mechanical support post-MI: globally restraining one or both ventricles, or locally reinforcing only the infarct area. Several ventricular restraint devices and a variety of local reinforcement approaches are compared and evaluated for their ability to reduce left ventricular remodeling and improve cardiac function following myocardial infarction. A variety of metrics used to quantify cardiac function are discussed, including limitations of frequently used functional indices. Differences in efficacy between synthetic and cell-seeded or tissue engineered patches for local reinforcement are investigated, followed by a brief discussion of the importance of patch material properties. Finally, methods for optimizing the type and degree of reinforcement are presented, including both experimental and computational approaches.
The first review on biomaterials for the treatment of myocardial infarction (MI) was written in 2006. In the last 5 years, the general approaches for biomaterial treatment of MI and subsequent left ventricular remodeling remain the same, namely, left ventricular restraints, epicardial patches, and injectable therapies. Nonetheless, there have been significant developments in this field, including advancement of biomaterial therapies to large animal pre-clinical studies and, more recently, to clinical trials. This review focuses on the progress made in the field of cardiac biomaterial treatments for MI over the last 5 years.
Myocardial infarction initiates progressive changes in the biology of the myocyte and nonmyocyte components of the myocardium, as well as the geometry of the left ventricle. Despite the use of evidence-based strategies to postmyocardial infarction, heart failure supervenes and is attended by an unacceptably high mortality rate. Given that left ventricular (LV) remodeling may contribute independently to disease progression, several innovative approaches have been designed to attenuate and reverse LV remodeling. This review discusses the emerging role of epicardial restraint devices in the treatment of postmyocardial cardiac remodeling.
Sudden death is prevalent in heart failure patients. We tested an implantable ventricular support device consisting of a wireform harness with one or two pairs of integrated defibrillation electrode coils.
The device was implanted into six pigs (36-44 kg) through a subxiphoid incision. Peak voltage (V) defibrillation thresholds (DFT) were determined for five test configurations compared with a control transvenous lead (RV to CanPect). Defibrillator can location (abdominal or pectoral) and common coil separation on the implant (0 degrees or 60 degrees ) were studied.(.) The DFT for RV60 to LV60 + CanPect was significantly less than control (348 +/- 57 vs 473 +/- 27 V, P < 0.05). The DFTs for other vectors were similar to control except for RV0 to LV0 + CanAbd (608 +/- 159 V). The device was implanted into 12 adult dogs for 42, 90, or 180 days with DFT and pathological examination performed at the terminal study. Cardiac pressures were determined at baseline, after implantation, and at the terminal study. The DFT was also determined in a separate group of four dogs at 42 days following implantation of the support device with one pair of defibrillation electrodes. The DFTs at implant and explant in dogs with one pair (8 +/- 1.5 Joules [J] and 6 +/- 1.9 J) or two pairs (8 +/- 3.4 J and 7 +/- 1.9 J) of defibrillation electrodes were not significantly different from each other but significantly less than control measured at the terminal study (18 +/- 3.4 J). Left-sided pressures were significantly decreased at explant but within expected normal ranges. Right-sided pressures were not different except for RV systolic. Histopathology indicated mild to moderate epicardial inflammation and fibrosis, consistent with a foreign body healing response.
This defibrillation-enabled ventricular support system maintained mechanical functionality for up to 6 months while inducing typical chronic healing responses. The DFT was equal to or lower than a standard transvenous vector.
Endothelial dysfunction in coronary circulation is well documented in heart failure (HF). However, whether this dysfunction is a consequence of heart failure or precedes the development of HF remains unknown. To determine endothelium-dependent regulation in the remote coronary vasculature in a canine coronary microembolization-induced HF model, seven dogs were chronically instrumented for measurement of systemic hemodynamics, for selective coronary microembolization via an implanted coronary catheter and for measurement of coronary blood flow in the non-embolized coronary artery. Microembolizations were performed daily until hemodynamic and echocardiographic measurements showed HF. The responses of coronary blood flow to acetylcholine (0.25, 0.5, 5, 10 microg/kg), nitroglycerin (0.2, 0.8, 5, 25 microg/kg), adenosine (0.25, 0.5, 2, 5 micromol/kg) and brief coronary occlusions (5, 10, 15, 20, 30 s) were examined. Although no signs of HF developed and the responses of coronary blood flow to nitroglycerin, adenosine and occlusions were not altered, the response to acetylcholine was selectively reduced after 1 week of embolization (275,000+/-55,000 microspheres). Resting coronary flow increased from 21.3+/-1.4 ml/min in control state to 27.7+3.5 ml/min (P<0.001). As HF developed, characterized by an elevated left ventricular end-diastolic pressure (6.4+/-1.6 v 16+/-1.6 mmHg, P<0.001), a decreased area ejection fraction (54+/-5 v 36+/-5%, P<0.05) and a reduced beta-adrenergic response to isoproterenol, the responses of coronary blood flow to acetylcholine, nitroglycerine, adenosine and occlusions were consistently depressed. Resting coronary blood flow was decreased to 15.4+/-2.7 ml/min (P<0.01). Our results indicate, that there is a selectively impaired endothelium-mediated dilator capacity of the resistance coronary vasculature before the development of HF and a reduction of the coronary flow reserve.
The role of the Frank-Starling mechanism in the regulation of cardiac systolic function in the ischemic failing heart was examined in conscious dogs. Left ventricular (LV) dimension, pressure and systolic function were assessed using surgically implanted instrumentations and non-invasive echocardiogram. Heart failure was induced by daily intra-coronary injections of microspheres for 3-4 weeks via implanted coronary catheters. Chronic coronary embolization resulted in a progressive dilation of the left ventricle (12+/-3%), increase in LV end-diastolic pressure (118+/-19%), depression of LV dP/dt(max) (-19+/-4%), fractional shortening (-36+/-7%), and cardiac work (-60+/-9%), and development of heart failure, while the LV contractile response to dobutamine was depressed. A brief inferior vena caval occlusion in dogs with heart failure decreased LV preload to match the levels attained in their control state and caused a further reduction of LV dP/dt(max), fractional shortening, stroke work and cardiac work. Moreover, in response to acute volume loading, the change in the LV end-diastolic dimension-pressure (DeltaLVEDD-DeltaLVEDP) curve in the failing heart became steeper and shifted significantly to the left, while the increases in LV stroke work and cardiac work were blunted. Thus, our results suggest that the Frank-Starling mechanism is exhausted in heart failure and unable to further respond to increasing volume while it plays an important compensatory role in adaptation to LV dysfunction in heart failure.
Infarct expansion after myocardial infarction results in early ventricular enlargement and distortion of ventricular geometry. To characterize the components of late volume enlargement, biplane left ventriculography was performed in 52 patients 3 weeks and 1 year after a first anterior myocardial infarction. Biplane diastolic circumference and contractile and noncontractile segment lengths were measured. Global geometry was evaluated by using a sphericity index (angiographic volume of the ventricle divided by the volume of a sphere with the same circumference). Regional geometry was assessed by measurement of endocardial curvature, an important determinant of wall tension.
This study reports hemodynamic, electrophysiologic, and clinical results in 171 patients (157 men and 14 women, mean age 57 +/- 8 years) 1 year after endoventricular circular patch repair and coronary grafting for postinfarction left ventricular dyskinetic or akinetic aneurysm. All patients had hemodynamic and electrophysiologic study before the operation and early and 1 year after the operation. The vast majority of aneurysms were anterior (n = 166), with a mean delay from infarction of 43 +/- 50 months. Fifty-two percent of patients were in New York Heart Association class III or IV, and preoperative ejection fraction was less than 40% in the majority of them (75%). Preoperative clinical ventricular tachycardia was present in 25 patients and was inducible in 59 patients. All patients had endoventricular circular patch repair with a synthetic (n = 99) or autologous patch (n = 72); 96% had associated coronary grafting with a mean number of bypass grafts of 1.9 +/- 0.9. Results at 1 year demonstrated a significant increase in ejection fraction (from 36% +/- 13% to 46% +/- 12% (p < 0.0001) and a significant reduction in ventricular volumes (end-diastolic volume index from 116 +/- 5 to 94 +/- 29 ml/m2 and end-systolic volume index from 77 +/- 45 to 53 +/- 25 ml/m2, p < 0.0001). New York Heart Association functional classification was significantly improved (2.6 +/- 0.9 vs 1.4 +/- 0.6, p < 0.0001) and ventricular tachycardias were almost suppressed (no documented clinical ventricular tachycardias and 8% incidence of inducible ventricular tachycardias after 1 year, chi 2 < 0.001). Patients who benefit most from the operation are those with more severe preoperative left ventricular dysfunction (i.e., ejection fraction < 30%), more frequent ventricular arrhythmias, and larger ventricular volumes. At regression analysis, critical disease of the right coronary artery was the only independent predictor of unsatisfactory pump improvement (as evaluated by postoperative increase of ejection fraction < 10 absolute points). In conclusion, in our large series of patients operated on by one surgical team between 1988 and 1993, who were studied hemodynamically both before and after the operation, endoventricular circular patch repair of left ventricular aneurysm associated with coronary grafting definitely improves left ventricular pump function and clinical status 1 year after the operation.
Left ventricular enlargement and the development of chronic heart failure are potent predictors of survival in patients after myocardial infarction. Prospective studies relating progressive ventricular enlargement in individual patients to global and regional cardiac dysfunction and the onset of late chronic heart failure are not available. It was the aim of this study to define the relation between left ventricular dilatation and global and regional cardiac dysfunction and to identify early predictors of enlargement and chronic heart failure in patients after myocardial infarction.
Left ventricular volumes, regional area shrinkage fraction in 18 predefined sectors (gated single photon emission computed tomography), global ejection fraction, and hemodynamics at rest and during exercise (supine bicycle, 50 W, 4 minutes, Swan-Ganz catheter) were assessed prospectively 4 days, 4 weeks, 6 months, and 1.5 and 3 years after first myocardial infarction. Seventy patients were assigned to groups with progressive, limited, or no dilatation. Patients without dilatation (n = 38) maintained normal volumes and hemodynamics until 3 years. With limited dilatation (n = 18), left ventricular volume increased up to 4 weeks after infarction and stabilized thereafter; depressed stroke volume was restored 4 weeks after infarction and then remained stable at rest. Wedge pressure during exercise, however, progressively increased. With progressive dilatation (n = 14), depressed cardiac and stroke indexes were also restored by 4 weeks but progressively deteriorated thereafter. Area shrinkage fraction as an estimate of regional left ventricular function in normokinetic sectors at 4 days gradually deteriorated during 3 years, but hypokinetic and dyskinetic sectors remained unchanged. Global ejection fraction fell after 1.5 years, whereas right atrial pressure, wedge pressure, and systemic vascular resistance increased. By multivariate analysis, ejection fraction and stroke index at 4 days, ventriculographic infarct size, infarct location, and Thrombolysis in Myocardial Infarction trial grade of infarct artery perfusion were significant predictors of progressive ventricular enlargement and chronic dysfunction.
Almost 26% of patients may develop limited left ventricular dilatation within 4 weeks after first infarction, which helps to restore cardiac index and stroke index at rest and to preserve exercise performance and therefore remains compensatory. A somewhat smaller group (20%) develops progressive structural left ventricular dilatation, which is compensatory at first, then progresses to noncompensatory dilatation, and finally results in severe global left ventricular dysfunction. In these patients, depression of global ejection fraction probably results from impairment of function of initially normally contracting myocardium. Early predictors from multivariate analysis allow identification of patients at high risk for progressive left ventricular dilatation and chronic ventricular dysfunction within 4 weeks after acute infarction.
Myocardial mechanics and energetics were investigated in an animal model of moderate chronic heart failure (CHF) created by repeated coronary microembolizations in six dogs. The final fractional area change was 34 +/- 4%. Hearts of these animals were isolated and cross-perfused, and balloons were placed in the left ventricle (LV). Chamber contractile state was markedly depressed in embolized hearts as assessed by the slope (Ees 2.74 +/- 0.49 vs. 4.00 +/- 1.18 mmHg/ml, P < 0.01) and volume axis intercept (V: 8.7 +/- 5.9 vs. 1.0 +/- 3.2 ml, P < 0.01) of end-systolic pressure-volume relation compared with a group of six normal dogs. The end-diastolic pressure-volume relation of embolized hearts was shifted to the right, indicating a dilation of the LV. However, systolic and diastolic stress strain relationships were similar in the two groups, suggesting that the average myocardial properties of the embolized hearts are similar to those of normal hearts. The relationship between oxygen consumption and pressure-volume area in embolized hearts had smaller intercept (2.98 +/- 0.44 vs 3.92 +/- 0.39 x 10(-2) ml O2.beat-1.100 g LV-1, P < 0.01) compared with the control group, with no change in the slope. These results contrast with previous findings in pacing CHF and serve as an important characterization of ventricular properties in this model of CHF from different etiology.
It is reasoned that reducing left ventricular diameter (Laplace's law) in patients with dilated cardiomyopathy, will improve ventricular function.
Partial left ventriculectomy was performed in 120 patients with end-stage dilated cardiomyopathies of varying causes. Most patients were in New York Heart Association functional class IV. The procedure consisted of removal of a wedge of left ventricular muscle from the apex to the base of the heart. Depending on the distance between the two papillary muscles, the mitral valve apparatus was either preserved, repaired, or replaced with a tissue prosthesis.
The 30-day mortality was 22% and the 2-year survival was 55%. Although 10% of surviving patients showed no improvement in New York Heart Association functional class, most of the surviving patients were in either class I (57%) or II (33.3%), and the others were in class III and IV.
Partial left ventriculectomy can be used to treat end-stage dilated cardiomyopathy. Further studies and a longer follow-up period are needed to fully assess the effects of this procedure.
Many believe that dyskinesia is the only predictor of favorable surgical outcome after large myocardial infarction and that akinetic scars do not recover well in patients with globally depressed ventricular function.
This study evaluates clinical and hemodynamic results of endoventricular circular patch plasty in patients with either large akinetic scar (n = 51) or large dyskinetic scar (n = 49) and depressed left ventricular function (ejection fraction <30%). Groups were comparable for symptoms, indication for operation, and delay from myocardial infarction. Heart failure was a major indication for operation in both groups. Coronary grafting was performed in 98% of patients: 10 had mitral valve repair or replacement, and 47 patients with preoperative ventricular arrhythmias had cryotherapy. In-hospital mortality was 12% (five patients in the akinetic group [10%] and seven in the dyskinetic group [14%]).
Results showed an early and late improvement in New York Heart Association functional class and ejection fraction (from 23% +/- 5% to 31% +/- 11% to 40% +/- 13% in akinetic patients and from 23% +/- 6% to 41% +/- 10% to 41% +/- 12% in dyskinetic patients). Ventricular tachycardia was reduced significantly in both groups early and late after the operation.
We conclude that in patients with either large akinetic or dyskinetic scar and severe left ventricular dysfunction, endoventricular circular patch plasty associated with coronary grafting and cryotherapy, when indicated, provides surviving patients with significant improvement in cardiac function. This approach can be considered as an alternative to heart transplantation in patients with severe left ventricular dysfunction.
We sought to evaluate regional morphology and function in patients in their first week after having a reperfused anterior myocardial infarction (MI) using magnetic resonance (MR) myocardial tagging.
The mechanism of myocardial dysfunction in the remote, noninfarct-related regions is an unresolved issue to date.
Sixteen patients with a first reperfused transmural anterior MI were studied with MR tagging at 5 +/- 2 days after the event, and the results were compared with those of an age-matched control group regions. The left ventricle (LV) was divided into infarct, adjacent and remote regions. Magnetic resonance tagging provided information on the regional ventricular morphology and function.
Morphologically, an increase of the circumferential radius of curvature was found in the remote myocardium, whereas the longitudinal radius of curvature was increased in all regions of the LV. A significant increase in apical sphericity was also found. A significant reduction in strain and function was found not only in the infarct region, but also in the adjacent and remote myocardium. The loss in regional ejection fraction in the remote myocardium (61.4 +/- 11.7% in patients vs. 68.7 +/- 10.0% in control subjects, p < 0.0001) was related to a significant reduction of the longitudinal and circumferential strain, whereas systolic wall thickening was preserved.
Remote myocardial dysfunction contributes significantly to the loss in global ventricular function. This could be secondary to morphologic changes in the infarct region, leading to an increased systolic longitudinal wall stress without loss of intrinsic contractility in the remote regions.
We sought to test the efficacy of a passive elastic containment device to reverse chronic chamber remodeling and adrenergic down-regulation in the failing heart, yet still maintaining preload reserve.
Progressive cardiac remodeling due to heart failure is thought to exacerbate underlying myocardial dysfunction. In a pressure-volume analysis, we tested the impact of limiting progressive cardiac dilation by an externally applied passive containment device on both basal and adrenergic-stimulated function in failing canine hearts.
Ischemic dilated cardiomyopathy was induced by repeated intracoronary microembolizations in six dogs. The animals were studied before and three to six months after surgical implantation of a thin polyester mesh (cardiac support device [CSD]) that surrounded both cardiac ventricles. Pressure-volume relations were measured by a conductance micromanometer catheter.
Long-term use of the CSD lowered end-diastolic and end-systolic volumes by -19 +/- 4% and -22 +/- 8%, respectively (both p < 0.0001) and shifted the end-systolic pressure-volume relation to the left (p < 0.01), compatible with reverse remodeling. End-diastolic pressure and chamber diastolic stiffness did not significantly change. The systolic response to dobutamine markedly improved after CSD implantation (55 +/- 8% rise in ejection fraction after CSD vs. -10 +/- 8% before CSD, p < 0.05), in conjunction with a heightened adenylyl cyclase response to isoproterenol. There was no change in the density or affinity of beta-adrenergic receptors. Diastolic compliance was not adversely affected, and preload-recruitable function was preserved with the CSD, consistent with a lack of constriction.
Reverse remodeling with reduced systolic wall stress and improved adrenergic signaling can be achieved by passive external support that does not generate diastolic constriction. This approach may prove useful in the treatment of chronic heart failure.
Left ventricular remodeling secondary to acute myocardial infarction (AMI) is characterized by ventricular dilatation and regional akinesis. In this study, we investigated the effect of passive constraint on akinetic area development.
The effect of passive constraint on akinetic area was investigated in 10 sheep using tissue-tagging magnetic resonance imaging (MRI). A baseline MRI study was followed by the creation of an anterior infarct. After 1 week, the animals received a second MRI study. A cardiac support device (CSD) was then placed over the epicardium in 5 sheep whereas the remaining animals served as controls. A terminal study was performed at the 2-month postinfarct in both groups. The akinetic area at 1-week postinfarct was similar in both groups. At the terminal time-point, the akinetic area in the control group was similar to the 1-week time-point whereas in the CSD group, the area of akinesis decreased (P=0.001). A comparison of the 2 groups at the terminal time-point demonstrates a significantly diminished area of akinesis in the CSD group (P=0.004). The relative area of akinesis followed a similar pattern. End-systolic and end-diastolic wall thickness was significantly greater in the CSD group at terminal (P=0.001). In addition, the minimum wall thickness was greater in the CSD group compared with the controls (P=0.04).
Passive constraint reduced akinetic area development secondary to AMI. The attenuation of regional wall stress may prevent the incorporation of the border zone into the infarct, decreasing infarct size and providing a promising new therapy for patients after an AMI.
Left ventricular (LV) remodeling occurs in patients with heart failure and is associated with poor long-term outcome. Two important components of this remodeling process are progressive LV dilation and LV shape changes, the latter manifested by increased LV chamber sphericity. This brief review describes two passive mechanical devices that were developed to prevent the progressive LV dilation and shape changes that occur during the evolution of heart failure. One such device is the Cardiac Support Device ([CSD] CorCap; Acorn Cardiovascular, St Paul, MN) and the other is the Myosplint (Myocor, Maple Grove, MN). Studies in dogs with coronary microembolization-induced heart failure have shown that the CSD prevents progressive LV dilation, increases LV ejection fraction, lowers LV wall stress, and attenuates LV chamber sphericity. Safety and feasibility studies in patients with heart failure have shown that the CSD is safe. The same studies have provided strong efficacy trends that are consistent with those seen in experimental animals. Studies in dogs with rapid pacing induced heart failure showed that the Myosplint device can reshape the LV leading to reduced LV volumes, increased ejection fraction, and reduced wall stress. Safety and feasibility studies of the Myosplint device in humans are limited and trends are not as yet easily discerned. Final conclusions on the clinical effectiveness of these devices must await completion of randomized clinical trials. These trials should provide the first tests in humans of the hypothesis that limiting LV remodeling alone can improve long-term outcome and quality of life in patients with heart failure.
We have shown that passive ventricular constraint during moderate heart failure can halt progressive deterioration in cardiac function in an experimental model of ovine pacing induced heart failure (HF). We report on ventricular constraint in severe heart failure.
Eighteen adult merino sheep were used. Severe heart failure was induced in two stages, ie, high rate ventricular pacing for 21 days to produce moderate HF and then for 42 days to induce severe HF. A custom-made polyester mesh cardiac support device ([CSD] Acorn Cardiovascular, St Paul, MN) was implanted snugly around both ventricles through a lower partial sternotomy in 9 sheep (group 1). Rapid ventricular pacing was continued for a further 28 days in all animals to induce advanced HF. Cardiovascular functional indicators were determined using echocardiography and a submaximal treadmill exercise protocol at base line, moderate, severe, and advanced stages. The 9 sheep in group 2 were used as controls.
Cardiovascular function was significantly depressed in all animals in advanced heart failure compared with base line, with left ventricular ejection fraction (LVEF) falling from 50% to 25% (p < 0.05) and LV +dp/dt((max)) declining from 1,777 to 1,243 (p < 0.05). However after CSD implantation cardiovascular function during exercise improved significantly despite ongoing rapid pacing, with LVEF increasing to 30% and LV +dp/dt to 1,499 (p < 0.05) in group 1. There were no significant changes in left ventricular long axis area (157 to 151 cm(2)) and short axis (6.8 to 6.1 cm) dimensions at the termination of pacing compared with those at time of CSD implant. Mitral regurgitation improved slightly from 2.5 to 2.19 after containment (p < 0.05) in group 1 but increased to 2.83 in group 2.
Ventricular constraint in advanced heart failure with a custom-made polyester mesh device halted the decline in cardiac function seen in untreated animals with this pacing-induced animal model of heart failure. These results indicate potential clinical implications for ventricular containment in the treatment of end-stage heart failure.
Passive mechanical containment of failing left ventricle (LV) with the Acorn Cardiac Support Device (CSD) was shown to prevent progressive LV dilation in dogs with heart failure (HF) and increase ejection fraction. To examine possible mechanisms for improved LV function with the CSD, we examined the effect of CSD therapy on the expression of cardiac stretch response proteins, myocyte hypertrophy, sarcoplasmic reticulum Ca2+-ATPase activity and uptake, and mRNA gene expression for myosin heavy chain (MHC) isoforms. HF was produced in 12 dogs by intracoronary microembolization. Six dogs were implanted with the CSD and 6 served as concurrent controls. LV tissue from 6 normal dogs was used for comparison. Compared with normal dogs, untreated HF dogs showed reduced cardiomyocyte contraction and relaxation, upregulation of stretch response proteins (p21ras, c-fos, and p38 alpha/beta mitogen-activated protein kinase), increased myocyte hypertrophy, reduced SERCA2a activity with unchanged affinity for calcium, reduced proportion of mRNA gene expression for alpha-MHC, and increased proportion of beta-MHC. Therapy with the CSD was associated with improved cardiomyocyte contraction and relaxation, downregulation of stretch response proteins, attenuation of cardiomyocyte hypertrophy, increased affinity of the pump for calcium, and restoration of alpha- and beta-MHC isoforms ratio. The results suggest that preventing LV dilation and stretch with the CSD promotes downregulation of stretch response proteins, attenuates myocyte hypertrophy and improves SR calcium cycling. These data offer possible mechanisms for improvement of LV function after CSD therapy.
To verify changes in left ventricular (LV) volumes and regional myocardial wall motion after implantation of a textile cardiac support device (CSD) for passive external constraint in non-ischemic dilated cardiomyopathy.
In nine male patients participating in a non-randomized clinical trial LV volumes were determined and the segmental LV wall motion was studied by contrast-enhanced electron-beam CT in a sectionwise manner at three ventricular levels (base, middle and apex of ventricle) before and 32+/-6 months after CSD implantation. In 16 myocardial segments ejection fraction and wall thickening were measured semiautomatically after drawing the myocardial contours. The wall motion score index was calculated based on semiquantitative visual grading in each segment.
The global LV volumes decreased significantly from 304.3 +/- 90.9 to 231.5 +/- 103.9 ml at end-diastole and from 239.7 +/- 83.7 to 164.0 +/- 97.7 at end-systole (P<0.05). Overall ejection fraction increased from 14.8 +/- 8.2 to 25.7 +/- 17.1% (P<0.05). A segment-by-segment analysis demonstrated a significant increase of regional ejection fraction in the basal myocardium as well as in the mid-inferior, mid-inferolateral, and mid-anterolateral myocardium. Overall wall thickening increased from 16.4 +/- 13.3 to 24.2 +/- 18.1% (P<0.05), but without significant differences in a segment-by-segment comparison. The mean wall motion score index improved from 2.70 +/- 0.26 to 2.20 +/- 0.71 (P<0.05), with an increased wall motion in eight (89%) patients. A section-by-section analysis demonstrated significantly improved wall motion in the inferior and lateral segments at each ventricular level. Postoperatively, the number of akinetic and markedly hypokinetic segments decreased significantly (P<0.05) from 56 (39%) to 26 (18%) and from 76 (53%) to 56 (37%), respectively.
CSD implantation improves segmental wall motion, predominantly in the inferior and lateral myocardium, and reduces the number of akinetic and hypokinetic segments.
The cardiac support device (CSD, Acorn) is a compliant, textile-mesh graft placed around the ventricles to prevent further dilatation and to improve function in congestive heart failure. The aim of this study was to verify post-operative changes in left ventricular volumes, ejection fraction, blood flow, and myocardial mass.
Fourteen patients underwent contrast-enhanced, electrocardiography-triggered electron-beam computerized tomography before and 6 to 9 months after CSD implantation. We measured volume and flow using the slice-summation method and the indicator-dilution technique.
We found significant changes for the following parameters: end-diastolic volume decreased from 382.9 +/- 140.2 ml to 311.3 +/- 138.7 ml, end-systolic volume from 310.4 +/- 132.4 ml to 237.4 +/- 133.8 ml, end-diastolic diameter from 75.3 +/- 7.8 mm to 70.7 +/- 11.6 mm, end-systolic diameter from 65.8 +/- 7.8 mm to 60.0 +/- 14.0 mm, and myocardial mass from 298.6 +/- 79.6 g to 263.1 +/- 76.8 g. Ejection fraction increased from 20.3% +/- 6.4% to 27.8% +/- 13.1%. We found no significant differences for stroke volume (from 72.5 +/- 24.6 ml to 73.8 +/- 23.6 ml), heart rate (from 80.5 +/- 11.0 beats per minute to 76.5 +/- 6.8 beats per minute), and total cardiac output (from 5.8 +/- 1.9 liter/min to 5.6 +/- 1.8 liter/min). Mitral regurgitation fraction decreased from 30.5% +/- 15.5% to 15.6% +/- 12.8%, increasing antegrade cardiac output from 3.8 +/- 0.9 liter/min to 4.7+/-1.5 liter/min. For most parameters, pre- and post-operative values in these patients differed significantly from those in an age- and gender-matched control group. In each patient, we observed a small hyperdense stripe along the pericardium after surgery, but we observed no local complications.
Three-dimensional structural and functional data obtained by computerized tomography volume and flow measurements confirm the safety and efficacy of CSD implantation.
Dynamic cardiomyoplasty has been performed in over 1000 patients worldwide but due to limited success the procedure was never been adopted as an alternative approach for the surgical therapy of heart failure. However, observations in these patients showed that the nonstimulated or fibrotic transformed latissimus dorsi by itself led to an improvement of heart failure symptoms. These findings stimulated animal experiments with so-called passive cardiomyoplasty devices. In several animal models, the progression of heart failure could be stopped, and even reversed remodeling could be demonstrated. Several different devices have been developed and tested in animal models. The Acorn CorCap has already passed a successful clinical feasibility study. However, the final evaluation of two multicenter trials has to be awaited to assess the future role of this device in the treatment of heart failure.
This article provides information and a commentary on landmark trials presented at the American Heart Association meeting held in November 2004, relevant to the pathophysiology, prevention, and treatment of heart failure. An open trial of the ACORN Cardiac Support Device (CSD) showed encouraging preliminary results in patients with severe heart failure. The PEACE (Prevention of Events with Angiotensin-Converting Enzyme inhibition) study supports data from previous studies showing that ACE inhibitors reduce vascular events in patients at increased risk. The CREATE (clinical trial of metabolic modulation in acute MI treatment evaluation) study of patients with acute myocardial infarction (MI) showed no mortality benefit of a glucose/insulin/potassium regimen, but treatment with reviparin reduced the incidence of death, MI, or stroke. Azimilide was not associated with a significant reduction in shocks, but reduced the shocks or episodes of markedly symptomatic ventricular tachycardia terminated by pacing in the SHIELD (Shock Inhibition Evaluation with Azimilide) study. The addition of isosorbide dinitrate plus hydralazine to standard therapy improved survival in black heart failure patients in the A-HeFT (African-American Heart Failure Trial) study. In an investigation of hypertensive patients with diabetes, carvedilol had fewer adverse effects on diabetic control than metoprolol. A meta-analysis of high-dose vitamin E supplementation suggested an association with increased mortality. The ESCAPE (Evaluation Study of CHF and Pulmonary Artery Catheterisation Effectiveness) study showed no benefit of pulmonary artery catheterisation over clinical management in patients with severe heart failure. Routine prophylactic coronary revascularisation for stable coronary disease prior to major vascular surgery showed no benefit in the CARP (Coronary Artery Revascularization Prophylaxis) study. Analysis of data from SCD-HeFT supports the cost-effectiveness of ICDs in heart failure, although overall cost implications may be prohibitive.
Previous studies have suggested that autologous skeletal myoblast transplantation (ASMT) improves left ventricular (LV) function in small animals after myocardial infarction. We tested the effects of ASMT on hemodynamics, LV function and remodeling in coronary microembolization-induced chronic heart failure (CHF) in conscious dogs.
Nineteen dogs were continuously instrumented with LV pressure sensors and mid-myocardial sonomicrometry crystals for dP/dt(max) and LV volume determination. Each dog underwent baseline assessment in a conscious state. CHF (20% to 30% reduction in dP/dt(max) and LV end-diastolic pressure >16 mm Hg) was created by daily coronary microembolizations via a continuously implanted coronary catheter. Skeletal muscle biopsy was performed and myoblasts were isolated and expanded. Then 2.7 x 10(8) to 8.3 x 10(8) myoblasts were injected into the infarcted region of 11 dogs after establishment of CHF. Saline injection (sham) was performed in 8 control dogs. Animals were evaluated every 2 weeks for up to 10 weeks. Global ejection fraction was determined by echocardiography. The end-systolic pressure-end-systolic volume relationship (ESPVR) was analyzed by the Sonomicrometic system.
Compared with saline injection, ASMT significantly increased dP/dt(max) (105 +/- 9% vs 97 +/- 7%, values were expressed as percentage change from baseline CHF, p = 0.013) and ejection fraction (46 +/- 3% vs 40 +/- 2%, p = 0.034) at 10 weeks after myoblast transplantation. There was a significant leftward and upward shift of the ESPVR back toward normal at 10 weeks after myoblast transplantation (p = 0.034). Three animals labeled with BrdU myoblasts showed no histologic evidence of viable engraftment.
ASMT provided mild improvements in hemodynamics and LV function and reduced LV remodeling in conscious dogs with CHF.
Effects of passive cardiac containment on left ventricular structure and function: verification by volume and flow measurements
- A Lembcke
- T Wiese
- S Dushe
- H Holtz
- C N Enzweiler
- B Hamm
- W F Konertz
Lembcke A, Wiese T, Dushe S, Holtz H, Enzweiler CN, Hamm B, Konertz
WF. Effects of passive cardiac containment on left ventricular structure
and function: verification by volume and flow measurements. J Heart
Lung Transplant 2004;23:11-9.
Socks for the dilated heart
- Gummert
Ventricular constraint using the acorn cardiac support device reduces myocardial akinetic area in an ovine model of acute infarction
- J. Pilla
- A.S. Blom
- D.J. Brockman
- F. Bowen
- Q. Yuan
- J. Gainmarco
- V.A. Ferrari
- J.H. Gorman
- R.C. Gorman
- M.A. Acker
Remote myocardial dysfunction after acute anterior myocardial infarction; impact of left ventricular shape on regional function
- J. Bogeart
- H. Bosmans
- A. Maes
- P. Suetens
- G. Marchal
- F.E. Rademakers
Bogeart J, Bosmans H, Maes A, Suetens P, Marchal G, Rademakers FE.
Remote myocardial dysfunction after acute anterior myocardial infarction; impact of left ventricular shape on regional function. J Am Coll
Cardiol 2000;35:1525-34.
Clinical trials update from the American Heart Association meeting
- R.J. Shelton
- P. Velavan
- N.P. Nikitin
- A.P. Coletta
- A.L. Clark
- A.S. Rigby
- N. Freemantle
- J.G.F. Cleland