Value-Based Payment for Clinicians Treating Cardiovascular Disease: A Policy Statement From the American Heart Association.

Clinician payment is transitioning from fee-for-service to value-based payment, with reimbursement tied to health care quality and cost. However, the overarching goals of value-based payment-to improve health care quality, lower costs, or both-have been largely unmet. This policy statement reviews the current state of value-based payment and provides recommended best practices for future design and implementation. The policy statement is divided into sections that detail different aspects of value-based payment: (1) key program design features (patient population, quality measurement, cost measurement, and risk adjustment), (2) the role of equity during design and evaluation, (3) adjustment of payment, and (4) program implementation and evaluation. Each section introduces the topic, describes important considerations, and lists examples from existing programs. Each section includes recommended best practices for future program design. The policy statement highlights 4 key themes for successful value-based payment. First, programs should carefully weigh the incentives between lowering cost and improving quality of care and ensure that there is adequate focus on quality of care. Second, the expansion of value-based payment should be a tool for improving equity, which is central to quality of care and should be a focal point of program design and evaluation. Third, value-based payment should continue to move away from fee for service toward more flexible funding that allows clinicians to focus resources on the interventions that best help patients. Last, successful programs should find ways to channel clinicians' intrinsic motivation to improve their performance and the care for their patients. These principles should guide the future development of clinician value-based payment models.

Expression of profibrotic genes in a murine remnant kidney model.

PURPOSE: To test the hypothesis that there is increased expression of several profibrotic genes, including matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2), a disintegrin and metalloproteinase with thrombospondin motif-1 (ADAMTS-1), and fibroblast specific protein-1 (FSP-1) in a murine remnant kidney model. MATERIALS AND METHODS: Chronic kidney disease (CKD) was created in 10 C57BL/6 male mice (20-25 g) by performing a right nephrectomy and ligation of the upper pole of the left kidney (remnant kidney). Animals were sacrificed 42 days and 56 days later. Reverse transcriptase polymerase chain reaction (RT-PCR) for MMP-2, MMP-9, TIMP-1, TIMP-2, ADAMTS-1, and FSP-1 was performed in the remnant kidney. Histologic evaluation of the remnant kidney was performed using Ki-67, α-smooth muscle cell actin (α-SMA), hematoxylin and eosin, and Masson' trichrome staining. Kidney function was assessed using serum blood urea nitrogen (BUN) and creatinine. RESULTS: The mean serum BUN and creatinine levels at day 42 and day 56 were significantly higher than baseline (P < .05). By day 42, the mean expression of MMP-2, MMP-9, TIMP-1, ADAMTS-1, and FSP-1 was significantly higher in the remnant kidney compared with the normal kidney (P < .05); by day 56, only FSP-1 expression was significantly higher (P < .05). There was increased fibrosis by Masson' trichrome, increased Ki-67, and increased α-SMA staining in the remnant kidney compared with the normal kidney. CONCLUSIONS: In the remnant kidney, there was increased fibrosis with increased α-SMA and Ki-67 staining and significantly increased expression of MMP-2, MMP-9, TIMP-1, ADAMTS-1, and FSP-1.

Vascular endothelial growth factor-A, matrix metalloproteinase-1, and macrophage migration inhibition factor changes in the porcine remnant kidney model: evaluation by magnetic resonance imaging.

PURPOSE: To determine the expression of vascular endothelial growth factor-A (VEGF-A), macrophage migration inhibition factor (MIF), and matrix metalloproteinase-1 (MMP-1) in the porcine remnant kidney model and quantify renal blood flow and volume using phase contrast magnetic resonance (PC MR) imaging with MR angiography. MATERIALS AND METHODS: In 23 pigs, the left renal artery was completely embolized using polyvinyl acrylide (PVA) particles and the right kidney partially embolized (remnant kidney), and six pigs served as controls. The animals were killed early (day 3, 7, and 14, N=3), day 24 (D24, N=5), day 37 (D37, N=3), day 42 (D42, N=9), and day 84 (D84, N=3). MR imaging/PC MR angiography of the kidneys was performed before death. The remnant and control kidneys were harvested for Western blotting of VEGF-A, MMP-1, and MIF. Blood was removed for blood urea nitrogen (BUN) and creatinine before embolization and at time of death. RESULTS: The kidney function after the embolization was characterized by chronic renal insufficiency. The renal artery blood flow, volume, and weight of the remnant kidney increased significantly over time when compared with controls. At early time points, there was increased expression of MIF and MMP-1 followed by an increase in the expression of VEGF-A by day 37 (P<.05 when compared with control). Masson's trichrome staining of the remnant kidney showed scarring in the tubulointerstitial space. CONCLUSIONS: In this model, renal blood flow and volume increase as the remnant kidney hypertrophies and scars. There is increased expression of MIF, VEGF-A, and MMP-1 in the remnant kidney.

Increased expression of HIF-1alpha, VEGF-A and its receptors, MMP-2, TIMP-1, and ADAMTS-1 at the venous stenosis of arteriovenous fistula in a mouse model with renal insufficiency.

PURPOSE: A mouse model of renal insufficiency with arteriovenous fistula (AVF) and venous stenosis was created. The authors tested the hypothesis that there is increased gene expression of hypoxia-inducible factor-1 alpha (HIF-1alpha); vascular endothelial growth factor-A (VEGF-A) and its receptors (VEGFR-1, -2); matrix metalloproteinase-2 (MMP-2), -9 (MMP-9); tissue inhibitor of metalloproteinase-1, -2 (TIMP-1, -2); and a disintegrin and metalloproteinase thrombospondin-1 (ADAMTS-1) at the venous stenosis. MATERIALS AND METHODS: Nineteen male C57BL/6 mice underwent a left nephrectomy and a surgical occlusion of the right upper pole to induce renal function characterized in eight animals. Twenty eight days later, an AVF (n = 11) was created from the right carotid artery to ipsilateral jugular vein, and the mice were killed at day 7 (n = 4) and day 14 (n = 4). The outflow and control veins were removed for gene expression. Three mice were killed at day 28 for histologic analysis. RESULTS: The mean serum blood urea nitrogen level remained significantly elevated for 8 weeks when compared with baseline (P < .05). By day seven, there was a significant increase in the expression of HIF-1alpha, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein, with HIF-1alpha and TIMP-1 levels significantly elevated at day 14 (P < .05). By day 28, the venous stenosis was characterized by a thickened vein wall and neointima. CONCLUSIONS: A mouse model of renal insufficiency with AVF was developed that had increased expression of HIF-1alpha, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein with venous stenosis by day 28.

Evolution of shear stress, protein expression, and vessel area in an animal model of arterial dilatation in hemodialysis grafts.

PURPOSE: To evaluate the wall shear stress, protein expression of matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2, and vessel area over time in a porcine model for polytetrafluoroethylene (PTFE) hemodialysis grafts. MATERIALS AND METHODS: In 21 pigs, subtotal renal infarction was created, and 28 days later, a PTFE graft was placed to connect the carotid artery to the ipsilateral jugular vein. Phase-contrast magnetic resonance imaging was used to measure blood flow and vessel area at 1, 3, 7, and 14 days after graft placement. Wall shear stress was estimated from the law of Poiseuille. Animals were killed at day 3 (n = 7), day 7 (n = 7), and day 14 (n = 7) and expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined at the grafted and control arteries. RESULTS: The mean wall shear stress of the grafted artery was higher than in the control artery at all time points (P < .05). It peaked by day 3 and decreased by days 7-14 as the vessel area nearly doubled. By days 7-14, there was a significant increase in active MMP-2 followed by a significant increase in pro-MMP-9 and active MMP-9 by day 14 (P < .05, grafted artery vs control). TIMP-1 expression peaked by day 7 and then decreased, whereas TIMP-2 expression was decreased at days 7-14. CONCLUSIONS: The wall shear stress of the grafted artery peaks by day 3, with increased MMP-2 activity by days 7-14, followed by increase pro-MMP-9 and active MMP-9 by day 14. In addition, the vessel area nearly doubled.

Hypoxia-induced phenotypic switch of fibroblasts to myofibroblasts through a matrix metalloproteinase 2/tissue inhibitor of metalloproteinase-mediated pathway: implications for venous neointimal hyperplasia in hemodialysis access.

PURPOSE: Hemodialysis grafts fail because of venous neointimal hyperplasia formation caused by adventitial fibroblasts that have become myofibroblasts (ie, alpha-smooth muscle actin [SMA]-positive cells) and migrate to the neointima. There is increased expression of hypoxia-inducible factor (HIF)-1alpha in venous neointimal hyperplasia formation in experimental animal models and clinical samples. It was hypothesized that, under hypoxic stimulus (ie, HIF-1alpha), fibroblasts will convert to myofibroblasts through a matrix metalloproteinase (MMP)-2-mediated pathway. MATERIALS AND METHODS: Murine AKR-2B fibroblasts were made hypoxic or normoxic for 24, 48, and 72 hours. Protein expression for HIF-1alpha, alpha-SMA, MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 was performed to determine the kinetic changes of these proteins. Immunostaining for alpha-SMA, collagen, and fibronectin was performed. RESULTS: At all time points, there was significantly increased expression of HIF-1alpha in the hypoxic fibroblasts compared with normoxic fibroblasts (P < .05). There was significantly increased expression of alpha-SMA at all time points, which peaked by 48 hours in hypoxic fibroblasts compared with normoxic fibroblasts (P < .05). There was a significant increase in the expression of active MMP-2 by 48-72 hours and a significant increase in TIMP-1 by 48-72 hours by hypoxic fibroblasts (P < .05). By 72 hours, there was significant increase in TIMP-2 expression (P < .05). Immunohistochemical analysis demonstrated increased expression of alpha-SMA, collagen, and fibronectin as the duration of hypoxia increased. CONCLUSIONS: Under hypoxic conditions, fibroblasts will convert to myofibroblasts through an MMP-2-mediated pathway, which may provide insight into the mechanism of venous neointimal hyperplasia.

Wall shear stress measurement using phase contrast magnetic resonance imaging with phase contrast magnetic resonance angiography in arteriovenous polytetrafluoroethylene grafts.

PURPOSE: The purpose of the present article was to determine the changes in luminal vessel area, blood flow, and wall shear stress in both the inflow artery and the venous stenosis of arteriovenous polytetrafluoroethylene (PTFE) grafts. METHODS AND MATERIALS: Polytetrafluoroethylene grafts were placed from the carotid artery to the ipsilateral jugular vein in 8 castrated juvenile male pigs. Contrast-enhanced magnetic resonance angiography (MRA) with cine phase-contrast magnetic resonance imaging (MRI) was performed 2 weeks after graft placement. RESULTS: The mean wall shear stress at the venous stenosis was 4 times higher than the control vein, while the inflow artery was only 2-fold higher. By day 14, venous stenosis had formed, which was characterized by narrowed area and elevated blood flow. CONCLUSION: By day 14, there is venous stenosis formation in porcine arteriovenous PTFE grafts with increased shear stress with decreased area when compared to control vein.