Reduced Myocardial Blood Flow During Left Ventricular Assist Device Support: A Possible Cause of Premature Bypass Graft Closure

Xydas, Steve; Rosen, Rebecca S.; Pinney, Sean; Hickey, Kathleen T.; Wasserman, Hal S.; Mancini, Donna; Naka, Yoshifumi; Öz, Mehmet C.; Bergmann, Steven R.; Maybaum, Simon

doi:10.1016/j.healun.2005.03.003

Cited by 16 publications

(8 citation statements)

References 8 publications

(8 reference statements)

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“…One possibility is that the myocardial microvessel growth is stimulated by mechanical and hemodynamic factors associated with increased blood flow (20). However, while cardiac output is increased by LVAD (as also found in our study), previous positron emission tomography studies have shown that this is not accompanied by increased coronary flow (21,22). Of note, in a Harefield group study, even though all subjects showed varying degrees of LVAD induced myocardial recovery, post LVAD coronary flow reserve was impressively impaired and the authors concluded that this finding required further investigation (21).…”

Section: Discussionsupporting

confidence: 89%

Impact of Mechanical Unloading on Microvasculature and Associated Central Remodeling Features of the Failing Human Heart

Drakos

Kfoury

Hammond

et al. 2010

Journal of the American College of Cardiology

127

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Objectives This study investigates alterations in myocardial microvasculature, fibrosis and hypertrophy before and after mechanical unloading of the failing human heart. Background Recent studies demonstrated the pathophysiologic importance and significant mechanistic links between microvasculature, fibrosis and hypertrophy during the cardiac remodeling process. The effect of left ventricular assist device (LVAD) unloading on cardiac endothelium and microvasculature is unknown and its influence on fibrosis and hypertrophy regression to the point of atrophy is controversial. Methods Hemodynamic data and left ventricular tissue were collected from patients with chronic heart failure at LVAD implant and explant (n=15), and from normal donors (n=8). New advances in digital microscopy provided a unique opportunity for comprehensive whole-field, endocardium-to-epicardium evaluation for microvascular density, fibrosis, cardiomyocyte size and glycogen content. Ultrastructural assessment was done with electron microscopy. Results Hemodynamic data revealed significant pressure unloading with LVAD. This was accompanied by a 33% increase in microvascular density (p=0.001) and a 36% decrease in microvascular lumen area (p=0.028). In agreement with these findings we also identified immunohistochemical ultrastructural evidence of endothelial cell activation. In addition, LVAD unloading significantly increased interstitial and total collagen content without any associated structural, ultrastructural or metabolic cardiomyocyte changes suggestive of hypertrophy regression to the point of atrophy and degeneration. Conclusions LVAD unloading resulted in increased microvascular density accompanied by increased fibrosis and no evidence of cardiomyocyte atrophy. These new insights into the effects of LVAD unloading on microvasculature and associated key remodeling features may guide future studies of unloading-induced reverse remodeling of the failing human heart.

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Section: Discussionsupporting

confidence: 89%

Impact of Mechanical Unloading on Microvasculature and Associated Central Remodeling Features of the Failing Human Heart

Drakos

Kfoury

Hammond

et al. 2010

Journal of the American College of Cardiology

127

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“…Very recently, it was shown that, according to perioperatively provided coronary angiography, 17% grafts are defected already during the surgery, with a need of revision for one-half of them [6]. Among other mechanisms leading to graft occlusion, reduced myocardial flow per se is prone to premature graft closure [25,26]. The competitive flow is of major importance, the unutilized grafts could be prone to occlusion [7].…”

Section: Discussionmentioning

confidence: 99%

Higher platelet activity is present in patients with restenosis after percutaneous coronary intervention compared with patients with an occlusion of coronary artery bypass graft

Osmančík

Bednář²,

Pavkova³

et al. 2008

Blood Coagulation &Amp; Fibrinolysis

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The aim of the study was to compare platelet activity between patients with an occlusion of bypass graft after coronary artery bypass graft surgery and restenosis after percutaneous coronary intervention (PCI); that is, between patients with reappearance of ischemia after two different kinds of coronary revascularization. Thirty patients were studied in a cross-sectional designed study. Fifteen of them were patients with the worst bypass graft patency from Prague-4 study (control protocol-driven coronary angiography performed at 1 year after surgery; originally 47 bypass grafts implanted, 94% of venous grafts occluded). The remaining 15 were patients with restenosis 3-12 months after PCI. Blood samples were drawn at least 12 weeks after coronary angiography. Platelet activity was determined by membrane expression of P-selectin (CD62P, % of positive cells) by flow cytometry, aggregability by ADP aggregometry. Data are expressed as mean +/- SEM. Both groups were similar with respect to age, BMI and presence of diabetes mellitus. No patient suffered from acute coronary syndrome. P-selectin expression was significantly higher in the patients with restenosis compared with patients with bypass graft occlusion (1.96 +/- 0.07 vs. 0.77 +/- 0.03, P < 0.001, Wilcoxon test). ADP aggregometry was not different between groups (55.5 +/- 1.1 vs. 56.1 +/- 0.8, P = NS). Higher platelet activity is present in the patients with restenosis after PCI compared with the patients with the occlusion of bypass graft. Platelet activity play more important role in the development of restenosis after PCI compared with the occlusion of bypass graft after coronary artery bypass graft surgery, at least in the period up to 1 year after revascularization.

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“…This is the first study to test the angiogenic properties of bone marrow cells in unloaded myocardium. Myocardial unloading by the LVAD results in decreased oxygen utilization by the heart (30) and other changes that may independently alter the angiogenic properties of the cardiac tissue (31). Furthermore, the aortic valve is closed during the majority of cardiac cycles and flow is nonpulsatile in LVAD patients, which may modulate flow-mediated signals for angiogenesis (32,33).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Bone Marrow−Derived Cell Therapy in Ischemic Cardiomyopathy With Left Ventricular Assist Device Bridge to Transplant

Stempien‐Otero

Helterline

Plummer

et al. 2015

Journal of the American College of Cardiology

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BACKGROUND Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation. OBJECTIVES We tested the hypothesis that bone marrow stem cells (CD34+) will improve histologic measurements of vascularity, fibrosis, and inflammation in human subjects undergoing left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation. METHODS Subjects with ischemic cardiomyopathy who were scheduled for placement of an LVAD as a bridge to transplantation underwent bone marrow aspiration the day prior to surgery; the bone marrow was processed into cell fractions (bone marrow mononuclear cells, CD34+, and CD34−). At LVAD implantation, all fractions and a saline control were injected epicardially into predetermined areas and each injection site marked. At transplant, injected areas were collected. Data were analyzed by paired Student t test comparing the effect of cell fractions injected within each subject. RESULTS Six subjects completed the study. There were no statistically significant differences in complications with the procedure versus control subjects. Histologic analysis indicated that myocardium injected with CD34+ cells had decreased density of endothelial cells compared to saline-injected myocardium. There were no significant differences in fibrosis or inflammation between groups; however, density of activated fibroblasts was decreased in both CD34+ and CD34− injected areas. CONCLUSIONS Tissue analysis does not support the hypothesis that bone marrow-derived CD34+ cells promote increased vascular tissue in humans with ischemic cardiomyopathy via direct injection.

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Reduced Myocardial Blood Flow During Left Ventricular Assist Device Support: A Possible Cause of Premature Bypass Graft Closure

Cited by 16 publications

References 8 publications

Impact of Mechanical Unloading on Microvasculature and Associated Central Remodeling Features of the Failing Human Heart

Impact of Mechanical Unloading on Microvasculature and Associated Central Remodeling Features of the Failing Human Heart

Higher platelet activity is present in patients with restenosis after percutaneous coronary intervention compared with patients with an occlusion of coronary artery bypass graft

Mechanisms of Bone Marrow−Derived Cell Therapy in Ischemic Cardiomyopathy With Left Ventricular Assist Device Bridge to Transplant

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