Stephen D Farris1, Creighton Don1, Deri Helterline1, Christopher Costa1, Tabitha Plummer1, Susanne Steffes2, Claudius Mahr1, Nahush A Mokadam3, April Stempien-Otero4. 1. University of Washington, Department of Medicine, Division of Cardiology, Seattle, Washington. 2. University of Washington, School of Nursing, Seattle, Washington. 3. University of Washington, Department of Cardiothoracic Surgery, Seattle, Washington. 4. University of Washington, Department of Medicine, Division of Cardiology, Seattle, Washington. Electronic address: april@u.washington.edu.
Abstract
BACKGROUND: Only limited data exist describing the histologic and noncardiomyocyte function of human myocardium in end-stage heart failure (HF). OBJECTIVES: The authors sought to determine changes in noncardiomyocyte cellular activity in patients with end-stage HF after left ventricular assist device (LVAD)-induced remodeling to identify mechanisms impeding recovery. METHODS: Myocardium was obtained from subjects undergoing LVAD placement and/or heart transplantation. Detailed histological analyses were performed, and, when feasible, mononuclear cells were isolated from fresh, dissociated myocardium for quantitative reverse transcription polymerase chain reaction studies. Echocardiographic and catheterization data were obtained during routine care. RESULTS: Sixty-six subjects were enrolled; 54 underwent 8.0 ± 1.2 months of LVAD unloading. Despite effective hemodynamic unloading and remodeling, there were no differences after LVAD use in capillary density (0.78 ± 0.1% vs. 0.9 ± 0.1% capillary area; n = 42 and 28, respectively; p = 0.40), cardiac fibrosis (25.7 ± 2.4% vs. 27.9 ± 2.4% fibrosis area; n = 44 and 31, respectively; p = 0.50), or macrophage density (80.7 ± 10.4 macrophages/mm2 vs. 108.6 ± 15 macrophages/mm2; n = 33 and 28, respectively; p = 0.1). Despite no change in fibrosis or myofibroblast density (p = 0.40), there was a 16.7-fold decrease (p < 0.01) in fibroblast-specific collagen expression. Furthermore, there was a shift away from pro-fibrotic/alternative pro-fibrotic macrophage signaling after LVAD use. CONCLUSIONS: Despite robust cardiac unloading, capillary density and fibrosis are unchanged compared with loaded hearts. Fibroblast-specific collagen expression was decreased and might be due to decreased stretch and/or altered macrophage polarization. Dysfunctional myocardium may persist, in part, from ongoing inflammation and poor extracellular matrix remodeling. Understanding these changes could lead to improved therapies for HF.
BACKGROUND: Only limited data exist describing the histologic and noncardiomyocyte function of human myocardium in end-stage heart failure (HF). OBJECTIVES: The authors sought to determine changes in noncardiomyocyte cellular activity in patients with end-stage HF after left ventricular assist device (LVAD)-induced remodeling to identify mechanisms impeding recovery. METHODS: Myocardium was obtained from subjects undergoing LVAD placement and/or heart transplantation. Detailed histological analyses were performed, and, when feasible, mononuclear cells were isolated from fresh, dissociated myocardium for quantitative reverse transcription polymerase chain reaction studies. Echocardiographic and catheterization data were obtained during routine care. RESULTS: Sixty-six subjects were enrolled; 54 underwent 8.0 ± 1.2 months of LVAD unloading. Despite effective hemodynamic unloading and remodeling, there were no differences after LVAD use in capillary density (0.78 ± 0.1% vs. 0.9 ± 0.1% capillary area; n = 42 and 28, respectively; p = 0.40), cardiac fibrosis (25.7 ± 2.4% vs. 27.9 ± 2.4% fibrosis area; n = 44 and 31, respectively; p = 0.50), or macrophage density (80.7 ± 10.4 macrophages/mm2 vs. 108.6 ± 15 macrophages/mm2; n = 33 and 28, respectively; p = 0.1). Despite no change in fibrosis or myofibroblast density (p = 0.40), there was a 16.7-fold decrease (p < 0.01) in fibroblast-specific collagen expression. Furthermore, there was a shift away from pro-fibrotic/alternative pro-fibrotic macrophage signaling after LVAD use. CONCLUSIONS: Despite robust cardiac unloading, capillary density and fibrosis are unchanged compared with loaded hearts. Fibroblast-specific collagen expression was decreased and might be due to decreased stretch and/or altered macrophage polarization. Dysfunctional myocardium may persist, in part, from ongoing inflammation and poor extracellular matrix remodeling. Understanding these changes could lead to improved therapies for HF.
Authors: Darrian Bugg; Logan R J Bailey; Ross C Bretherton; Kylie E Beach; Isabella M Reichardt; Kalen Z Robeson; Anna C Reese; Jagadambika Gunaje; Galina Flint; Cole A DeForest; April Stempien-Otero; Jennifer Davis Journal: Cell Stem Cell Date: 2022-02-16 Impact factor: 25.269
Authors: Palak Shah; Mitchell Psotka; Iosif Taleb; Rami Alharethi; Mortada A Shams; Omar Wever-Pinzon; Michael Yin; Federica Latta; Josef Stehlik; James C Fang; Guoqing Diao; Ramesh Singh; Naila Ijaz; Christos P Kyriakopoulos; Wei Zhu; Christopher W May; Lauren B Cooper; Shashank S Desai; Craig H Selzman; Abdallah G Kfoury; Stavros G Drakos Journal: Circ Heart Fail Date: 2021-05-05 Impact factor: 8.790