Structural and left ventricular histologic changes after implantable LVAD insertion

McCarthy, Patrick M.; Nakatani, Satoshi; Vargo, Rita L.; Kottke‐Marchant, Kandice; Harasaki, Hiroaki; James, Karen B.; Savage, Robert M.; Thomas, James D.

doi:10.1016/0003-4975(94)00953-8

Cited by 152 publications

(65 citation statements)

References 10 publications

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“…The most obvious clinical example of "reverse" LV remodeling is the striking change that occurs in the dilated cardiomyopathic ventricle after implantation of a LV assist device. The salutary changes that have been reported include increased LV wall thickness, 111 decreased LV volume, 112 and a favorable leftward shift in the LV pressure-volume curve. 112 Medical therapy has also been shown to halt and/or reverse LV remodeling in some patients.…”

Section: Are the Defects In The Geometry Of The Remodeled Left Ventrimentioning

confidence: 94%

Mechanisms and Models in Heart Failure

2005

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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.

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Section: Are the Defects In The Geometry Of The Remodeled Left Ventrimentioning

confidence: 94%

Mechanisms and Models in Heart Failure

2005

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“…68 Wavy myocardial fibers, especially when associated with focal edema, are characteristic signs of acute myocardial ischemia in humans 26 and in dogs, 26,27 but have also been described in human patients with DCM. 52,59 The myocardial lesions associated with the attenuated wavy fiber type of DCM consist of myocardial cells Ͻ6 m in diameter (normal myofiber diameter ranges from 10 to 20 m 92 ) with a wavy appearance, comprising at least half of the thickness of the myocardial specimens from the upper and lower portions of the left ventricular wall. The myocytes are separated by a clear space generally free from cellular infiltrates, suggestive of edematous fluid.…”

Section: Gross Pathology and Histopathologymentioning

confidence: 99%

Histologic Characterization of Canine Dilated Cardiomyopathy

Tidholm¹,

Jönsson

2005

Vet Pathol

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Abstract. Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the ''fatty infiltration-degenerative'' type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the ''attenuated wavy fiber'' type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.

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“…[1][2][3] Recent reports demonstrate that LVAD support may be associated with adaptive remodeling of the ventricular myocardium, including reduced LV mass, wall thickness, and myocyte diameter; changes in LV pressure-volume relationships; and reversal of LV chamber dilation and molecular remodeling of proteins involved in Ca 2ϩ cycling. [3][4][5][6][7][8][9][10] In addition, LVAD support has been associated with salutary changes in cardiomyocyte function. Indeed, a small subgroup of patients can be successfully weaned from LVAD after recovery of ventricular function.…”

Section: Conclusion-the Reduced Mmps and Increased Timps And Ratios mentioning

confidence: 99%

Downregulation of Matrix Metalloproteinases and Reduction in Collagen Damage in the Failing Human Heart After Support With Left Ventricular Assist Devices

et al. 2001

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Background-Left ventricular assist device (LVAD) support of the failing heart induces salutary changes in myocardial structure and function. Matrix metalloproteinases (MMPs) are increased in the failing heart and are induced by stretch in cardiac cells in vitro. We hypothesized that mechanical unloading may affect LV plasticity by regulating MMPs and their substrates. Methods and Results-LV samples were collected from patients with dilated cardiomyopathy (DCM, nϭ14) or ischemic cardiomyopathy (ICM, nϭ16) at the time of implantation of the LVAD and again during cardiac transplantation. MMP-1, -3, and -9 were measured by ELISA, MMP-2 and -9 gelatinolytic activity by gelatin zymography, and tissue inhibitors of metalloproteinases (TIMPs) by Western blot. Total soluble and insoluble collagens were separated by pepsin solubilization, and the contents were determined by quantification of hydroxyproline. The undenatured soluble collagen was measured by Sircol collagen assay. The results showed that MMP-1 and -9 were decreased, whereas TIMP-1 and -3 were increased, but there was no change in MMP-2 and -3 and TIMP-2 and -4 after LVAD support. The undenatured collagen was increased, with the ratio of undenatured to total soluble collagens increased in ICM and that of insoluble to total soluble collagens increased in DCM after LVAD support. Conclusions-The reduced MMPs and increased TIMPs and ratios of undenatured to total soluble collagens and insolubleto total soluble collagens after LVAD support suggest that reduced MMP activity diminished damage to the matrix. These changes may contribute to the functional recovery and LV plasticity after LVAD support. Key Words: collagen Ⅲ metalloproteinases Ⅲ remodeling Ⅲ heart-assist device Ⅲ heart failure L eft ventricular assist devices (LVADs) provide mechanical support for the failing heart and serve as a bridge to cardiac transplantation, with the potential to be a destiny therapy for heart failure. [1][2][3] Recent reports demonstrate that LVAD support may be associated with adaptive remodeling of the ventricular myocardium, including reduced LV mass, wall thickness, and myocyte diameter; changes in LV pressure-volume relationships; and reversal of LV chamber dilation and molecular remodeling of proteins involved in Ca 2ϩ cycling. [3][4][5][6][7][8][9][10] In addition, LVAD support has been associated with salutary changes in cardiomyocyte function. Indeed, a small subgroup of patients can be successfully weaned from LVAD after recovery of ventricular function. 6,[11][12][13][14] Although it has been suggested that these beneficial changes are attributed to chronic unloading of the ventricular myocardium, the molecular mechanisms that play a role in LVAD-induced myocardial plasticity and LV remodeling remain undefined. See p 1089We hypothesized that the myocardial remodeling that occurs with LVAD unloading might be attributable to alterations in the components of the extracellular matrix, and specifically in the activity of matrix metalloproteinases (MMPs) and the physical pr...

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Structural and left ventricular histologic changes after implantable LVAD insertion

Cited by 152 publications

References 10 publications

Mechanisms and Models in Heart Failure

Mechanisms and Models in Heart Failure

Histologic Characterization of Canine Dilated Cardiomyopathy

Downregulation of Matrix Metalloproteinases and Reduction in Collagen Damage in the Failing Human Heart After Support With Left Ventricular Assist Devices

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