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Ann Thorac Surg 2001;71:S185-S187
© 2001 The Society of Thoracic Surgeons
a Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York, USA
Address reprint requests to Dr Oz, Milstein 7-435, 177 Fort Washington Ave, New York, NY 10032
e-mail: mco2{at}columbia.edu
Presented at the Fifth International Conference on Circulatory Support Devices for Severe Cardiac Failure, New York, NY, Sept 15–17, 2000.
The underlying etiology of congestive heart failure may entail structural, biochemical, or physiological abnormalities. Regardless of the initiating insult, the heart compensates with a number of acute adaptive mechanisms to maintain adequate cardiac output [1]. Such adaptive mechanisms include cardiac dilation and activation of neurohormonal adjustments to maintain arterial pressure and perfusion of vital organs [2]. The chronic effect of these compensatory changes results in structural and functional changes to the heart, known as "remodeling" [3], that become a hallmark in the progression of heart failure.
Several factors can stimulate the remodeling process, including neurohormonal activation and mechanical stress. The compensatory ventricular dilation increases biomechanical wall stress and creates stretch of the cardiac myocytes [4]. Such stretch induces maladaptive changes in gene expression and stimulation of autocrine/paracrine neurohormonal activity, with adverse effects on the extracellular matrix and promotion of myocyte apoptosis [1, 5, 6]. Once begun, the remodeling process is auto-inductive, leading to further remodeling and progression of ventricular dysfunction and, baring intervention, inexorably to end-stage heart failure.
One surgical means of intervention is represented by the Acorn Cardiac Support Device (CSD), a mesh-like implantable device that is surgically positioned around the heart and adjusted to provide circumferential diastolic support. The CSD is intended to reduce wall stress and myocyte stretch during end-diastole and periodic hemodynamic overload conditions. By reducing or limiting the stress and stretch on the myocardium, a key component of the remodeling process may be halted or reversed.
Device and implantation/implant procedures
The CSD is made from a mesh-like polyester fabric (Fig 1). The fabric is constructed from a multifilamentous yarn to provide high-strength and fatigue characteristics, while maintaining flexibility. A knit construction was chosen for the fabric to impart tear and ravel resistance. The device is designed with bidirectional compliance to conform to the heart and assist in reshaping the heart to a more ellipsoidal shape. The CSD is available in six sizes with the final fitting performed by the surgeon for the specific heart.
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Preclinical studies
Preclinical study results with the CSD have been reported from two different heart failure models. Sabbah and associates [7] have reported reduced left ventricular volumes and improved cardiac function parameters in CSD-treated animals, compared with controls, using a microembolic canine model at 3-months of follow-up (Table 1). Ejection fraction and regional wall motion were greater in the CSD-treated group, while mitral valve regurgitation was eliminated in the treatment group. There was no evidence of constrictive physiology based on response to volume loading, and no indication of equalization in left and right heart filling pressures. Similar results were seen at 6-month follow-up.
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Other biochemical factors implicated in possible mechanisms of actions for the CSD therapy have been examined. Sabbah and associates [11] reported that stretch protein levels (p21ras, c-fos, p38
/ßMAP kinase) were at lower levels in the CSD-treated group, and Ca2+ cycling was improved (based on an increase in the ratio of Ca2+ ATPase/phospholamban) in the CSD-treated group. These findings suggest that the CSD can prevent or minimize maladaptive gene expression and phenotypic transformation. Further investigation of potential changes in the extracellular matrix, apoptosis, and local neurohormonal activity is currently underway. In summary, these studies indicate that the CSD, by supporting the ventricle and reducing stress-mediated myocardial stretch, can halt progressive remodeling and perhaps allow for reverse remodeling.
Clinical studies
A two-center clinical safety study has been undertaken and enrollment completed, to evaluate the feasibility and safety of the CSD as a treatment for dilated cardiomyopathy resulting from either ischemic or nonischemic etiologies. Patients enrolled in the study include those with previous myocardial infarctions, candidates for heart valve repair or replacement, patients receiving concomitant coronary artery bypass grafts, and patients with idiopathic cardiomyopathy.
A series of 21 safety study patients were enrolled at Charité Universitätsklinikum, Humboldt-Universität zu Berlin, Germany, between Apr and Sept 1999. Of the 21 patients, 7 required no additional cardiac surgery other than the CSD implantation, and the remainder had some type of concomitant cardiac surgery. The majority of these procedures were cardiac valve repair or replacement. Five safety study patients were also enrolled at the Austin and Repatriation Medical Centre, Melbourne, Australia, where all patients received coronary artery bypass grafts with no valve repair done. The Melbourne studies began in June 1999. As of this report, the average implant duration was 12 months at both study sites.
The 3- and 6-month follow-up evaluations from Charité demonstrate that the CSD effectively limits progressive cardiac dilation. In fact, average heart size actually decreased by statistically significant amounts, while average ejection fraction increased (Fig 3). Functional status and quality of life assessments, including New York Heart Association Class, Minnesota Living with Heart Failure, and Uniscale, all point towards improvement in quality of life for these patients. Trends were similar in patients that only received the CSD, including improvement or maintenance in cardiac performance with no impairment in coronary artery flow and no indication of constrictive physiology, and no device-related adverse events [12].
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Summary
Progressive heart failure is characterized by loss of cardiac function associated with maladaptive changes in myocardial gene expression and neuroendocrine activity, leading to progressive increases in heart size. Elevated ventricular wall stress results from an increase in chamber size, and is thought to play a role in furthering development towards end-stage disease. Reduction of wall stress and stress mediated myocardial stretch may be an important means for mitigating heart failure progression. One possible approach to accomplish this goal is through passive support of the heart with the Cardiac Support Device. Results from preclinical and clinical evaluation give support to this premise.
Acknowledgments
The author thanks Acorn Inc for financial support for these studies.
References
This article has been cited by other articles:
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  J. M. Aranda Jr, G. W. Woo, R. S. Schofield, E. M. Handberg, J. A. Hill, A. B. Curtis, S. F. Sears, J. S. Goff, D. F. Pauly, and J. B. Conti Management of Heart Failure After Cardiac Resynchronization Therapy: Integrating Advanced Heart Failure Treatment With Optimal Device Function J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2193 - 2198. [Abstract] [Full Text] [PDF]
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