Stabilization of Chronic Remodeling by Asynchronous Cardiomyoplasty in Dilated Cardiomyopathy

Patel, Himanshu J.; Polidori, David J.; Pilla, James J.; Plappert, Theodore; Kass, David A.; Sutton, Martin St. John; Lankford, Edward B.; Acker, Michael A.

doi:10.1161/01.cir.96.10.3665

Cited by 44 publications

(16 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the beneficial effects of LV assist devices on LV remodeling, a number of different surgical approaches have been tried to prevent and/or retard LV remodeling, including surgical myoplasty, which has largely been abandoned, 117 …”

Section: Remodeling As a Therapeutic Target In Heart Failurementioning

confidence: 99%

Mechanisms and Models in Heart Failure

2005

View full text Add to dashboard Cite

Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure, no single conceptual paradigm for heart failure has withstood the test of time. Whereas clinicians initially viewed heart failure as a problem of excessive salt and water retention that was caused by abnormalities of renal blood flow (the "cardiorenal model" 1 ), as physicians began to perform careful hemodynamic measurements, it also became apparent that heart failure was associated with a reduced cardiac output and excessive peripheral vasoconstriction. This latter realization led to the development of the "cardiocirculatory" or "hemodynamic" model for heart failure, 1 wherein heart failure was thought to arise largely as a result of abnormalities of the pumping capacity of the heart and excessive peripheral vasoconstriction. However, although both the cardiorenal and cardiocirculatory models for heart failure explained the excessive salt and water retention that heart failure patients experience, neither of these models explained the relentless "disease progression" that occurs in this syndrome. Thus, although the cardiorenal models provided the rational basis for the use of diuretics to control the volume status of patients with heart failure, and the cardiocirculatory model provided the rational basis for the use of inotropes and intravenous vasodilators to augment cardiac output, these therapeutic strategies have not prevented heart failure from progressing, nor have they led to prolonged life for patients with moderate to severe heart failure. 1,2 In the present review we will summarize recent advances in the field of heart failure, with a focus on the new therapeutic strategies that have been developed for treating systolic heart failure. For a complete discussion on recent advances in the diagnosis and treatment of diastolic heart failure, the interested reader is referred to several recent reviews on this topic. [3][4][5] To provide the proper framework for this discussion, we will review current and emerging therapies within the context of the extant conceptual biological models that clinician scientists have used for envisioning the syndrome of systolic heart failure. However, as discussed at the conclusion of this review, our current working models for heart failure are insufficient for explaining several of the new and emerging therapies for treating systolic heart failure. To this end, we suggest a simplified conceptual model for heart failure that both unites and extends several of the existing working models for heart failure.

show abstract

Section: Remodeling As a Therapeutic Target In Heart Failurementioning

confidence: 99%

Mechanisms and Models in Heart Failure

2005

View full text Add to dashboard Cite

show abstract

“…Even though the procedure involved extensive surgery and was plagued with technical difficulties, patients showed symptomatic improvement. 24,25 However, several experimental 26,27 and clinical 28 studies have suggested that the improvement was derived primarily from the passive girdling of the heart and not from active contraction of the skeletal muscle. Several studies in various animal models of HF have shown that progressive LV dilation can be prevented or attenuated by wrapping synthetic materials around the cardiac ventricles to elicit containment.…”

Section: Discussionmentioning

confidence: 99%

Reversal of Chronic Molecular and Cellular Abnormalities Due to Heart Failure by Passive Mechanical Ventricular Containment

Sabbah¹,

Sharov²,

Gupta³

et al. 2003

Circulation Research

102

View full text Add to dashboard Cite

Abstract-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 Ca 2ϩ -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 ␣/␤ mitogen-activated protein kinase), increased myocyte hypertrophy, reduced SERCA2a activity with unchanged affinity for calcium, reduced proportion of mRNA gene expression for ␣-MHC, and increased proportion of ␤-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 ␣-and ␤-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. Key Words: heart failure Ⅲ myocyte hypertrophy Ⅲ sarcoplasmic reticulum Ⅲ myosin heavy chain H eart failure (HF) is a progressive disorder mediated through multiple signaling pathways. Once initiated, HF is characterized by increased neurohumoral activation and ventricular dilation. Although such compensatory changes are initially beneficial, over the long-term they cause adverse structural and functional changes collectively referred to as ventricular remodeling. Ventricular dilation also causes increased mechanical stress and myocardial stretch. Upregulation of stretch response proteins, such as p21ras, 1 c-fos, 2,3 and p38 ␣/␤ mitogen-activated protein kinase (MAPK), 4 have been shown to induce cardiomyocyte hypertrophy.The Acorn Cardiac Support Device (CSD) has been shown to halt progressive left ventricular (LV) dilation and improve ejection fraction. [5][6][7] However, the mechanism(s) underlying the improved cardiac function has not been elucidated. In the present study, we tested the hypothesis that improvement in LV systolic function in dogs with HF after long-term therapy with the CSD results, in part, from downregulation of stretch response proteins, attenuation of cardiomyocyte hypertrophy, 1-4 and improvement of sarcoplasmic reticulum (SR) calcium cycling. To further understand the mechanisms for the improvement in LV systolic function, we also explored the influence of ...

show abstract

“…Animal [17][18][19][20] and clinical [21,22] studies of cardiomyoplasty support a conclusion that passive external constraint by the muscle wrap may halt or even reverse remodeling of the dilated ailing heart. It has been postulated that the constraining effect of cardiomyoplasty on the left ventricle E-mail: rwalsh@acorncv.com stabilizes cardiac function by limiting left ventricular volume, thus reducing chronic dilation and decreasing diastolic strain [23].…”

Section: Introductionmentioning

confidence: 86%

Design and Features of the Acorn CorCapTM Cardiac Support Device: The Concept of Passive Mechanical Diastolic Support

Walsh

2005

Heart Fail Rev

View full text Add to dashboard Cite

The Laplace equation points to the importance of ventricular wall stress as a factor in heart failure development and progression. Based on animal and clinical experience with active and passive cardiomyoplasty, a synthetic passive constraint was proposed as a means of reducing excessive wall stress, and thus assuaging disease progression. The Acorn CorCap CSD Cardiac Support Device was designed to provide passive diastolic support and serve as a constraint against chronic cardiac dilation in heart failure. Basic and uncomplicated in appearance, the device nevertheless incorporates numerous sophisticated structural and functional features intended maximize therapeutic value. The device is fabricated from medical grade multifilament polyester yarn, in a specific knit construction chosen to provide structural integrity, low physical profile, pliability for intimate contact with the epicardial surface, ease of manipulation during implantation, and anisotropic compliance characteristics to encourage beneficial reverse remodeling.

show abstract

Stabilization of Chronic Remodeling by Asynchronous Cardiomyoplasty in Dilated Cardiomyopathy

Cited by 44 publications

References 41 publications

Mechanisms and Models in Heart Failure

Mechanisms and Models in Heart Failure

Reversal of Chronic Molecular and Cellular Abnormalities Due to Heart Failure by Passive Mechanical Ventricular Containment

Design and Features of the Acorn CorCapTM Cardiac Support Device: The Concept of Passive Mechanical Diastolic Support

Contact Info

Product

Resources

About