Ignite Creation Date:
2024-05-06 @ 3:08 PM
Last Modification Date:
2024-10-26 @ 1:44 PM
Study NCT ID:
NCT04539093
Status:
COMPLETED
Last Update Posted:
2023-10-23
First Post:
2020-08-14
Brief Title:
Endothelial Function in Mechanical Circulatory Support
Sponsor:
Medical College of Wisconsin
Organization:
Medical College of Wisconsin
Study Overview
Official Title:
Assessment of Endothelial Function in Patients With Advanced Heart Failure Requiring Mechanical Circulatory Support
Status:
COMPLETED
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The pathophysiology of HF is highly variable with overlapping pathogenic mechanisms that complicates any attempt to create a simple and unified conceptual model Left ventricular LV ejection fraction EF assessed as the fraction of the end-diastolic volume that is ejected upon contraction has been the cornerstone metric for characterization of LV systolic function in patients with HF LVEF demonstrates a strong inverse relationship with clinical outcomes in HF in patients with reduced EF HFrEF Current management options for the treatment of HFrEF include medical management mechanical circulatory support and cardiac transplantation In the setting of refractory end stage HFrEF the standard of care is heart transplantation Since limited organ procurement is a significant constraint to the treatment of patients with advanced disease durable mechanical circulatory support MCS with left ventricular assist devices LVAD were developed as a safe and efficacious treatment strategy for patients with advanced HF that is refractory to medical therapy
The advances in LVAD engineering and design tailored towards defined physiological goals have resulted in the creation of much smaller continuous-flow CF pumps that possess technical superiority pump durability and ease of implantation compared to the older and larger pulsatile-flow pumps The addition of speed modulation algorithms to the next generation centrifugal CF LVADs has decreased the incidence of device related adverse events
Our interest lies in the impact of continuous flow hemodynamics on endothelial function and the cardiac and end-organ responses to this novel therapy Current knowledge of the impact of these specific advances in LVAD therapy is however limited by the relative youth of the field Thus the goal of this research project is to study human LVAD patients and to determine the impact of speed modulation algorithms in CF physiology on microvascular and endothelial function and its association with cardiac and peripheral organ function
The investigators hypothesize that restoration of cardiac output using an LVAD with modern speed modulation algorithm improves vascular endothelial function In addition these changes would have a positive correlation with functional outcomes
The advances in LVAD engineering and design tailored towards defined physiological goals have resulted in the creation of much smaller continuous-flow CF pumps that possess technical superiority pump durability and ease of implantation compared to the older and larger pulsatile-flow pumps The addition of speed modulation algorithms to the next generation centrifugal CF LVADs has decreased the incidence of device related adverse events
Our interest lies in the impact of continuous flow hemodynamics on endothelial function and the cardiac and end-organ responses to this novel therapy Current knowledge of the impact of these specific advances in LVAD therapy is however limited by the relative youth of the field Thus the goal of this research project is to study human LVAD patients and to determine the impact of speed modulation algorithms in CF physiology on microvascular and endothelial function and its association with cardiac and peripheral organ function
The investigators hypothesize that restoration of cardiac output using an LVAD with modern speed modulation algorithm improves vascular endothelial function In addition these changes would have a positive correlation with functional outcomes
Detailed Description:
The advances in LVAD engineering and design tailored towards defined physiological goals have resulted in the creation of much smaller CF pumps that possess technical superiority pump durability and ease of implantation compared to the older and larger PF pumps The addition of artificial pulsatility to the next generation centrifugal CF LVADs has decreased the incidence of device related adverse events However given the recent nature of these advances the physiologic impact has yet to be fully elucidated LVADs in general have demonstrated good outcomes and are rapidly gaining traction towards becoming standard therapy for refractory end stage HF The investigators are in a position to study this new technology and the impact of the resultant altered physiologic state
Our interest lies in the impact of continuous flow hemodynamics on endothelial function and the cardiac and end-organ responses to this novel therapy Basal homeostatic properties of healthy endothelium are in part based on the effects of hemodynamic forces such as hydrostatic pressure cyclic stretch and fluid shear stress which occur as a consequence of blood pressure and pulsatile blood flow in the vasculature Under ambient conditions these forces are generally atheroprotective and increase the expression of nitric oxide synthase eNOS to generate nitric oxide NO decrease reactive oxidative species ROS and oxidative stress decrease expression of proinflammatory adhesion molecules and maintain an antithrombotic surface Increases in shear stress stimulate compensatory expansion of the vessels and thereby return shear forces to basal levels Likewise a decrease in shear stress can narrow the lumen of the vessel in an endothelium-dependent manner In essence the vessel remodels itself in response to long-term changes in flow such that the luminal diameter is reshaped to maintain a constant predetermined level of shear stress The capacity of the endothelium to sense shear stress is therefore an important determinant of luminal diameter and overall vessel structure Failure to adapt to pathophysiological stimuli may lead to maladaptive responses that result in seemingly permanent alterations in endothelial phenotype and promote endothelial dysfunction This phenomenon plays an integral role in several cardiovascular disease processes Endothelial dysfunction of both microvascular and conduit arteries is a component of chronic heart failure and correlates with severity of disease Improvement in cardiac function whether via medical therapy or cardiac output augmentation can improve endothelial function and benefit patients through better peripheral vascular reactivity However much of the improvement in endothelial function is thought to be related to the pulsatile laminar flow that occurs in majority of vascular beds With the increasing use of CF pumps it has become clear that the lack of pulsatility adversely affects the endothelium by decreasing vessel wall shear stress reducing cyclic stretch that affects vascular cell proliferation disrupting endothelium-dependent vasodilation activating extrinsic pathway of thrombosis and heightening vascular inflammation The reintroduction of pulsatility through flow modulation control strategies could help mitigate these device specific issues and help promote endothelial recovery Our knowledge of the impact of these specific advances in LVAD therapy is however limited by the relative youth of the field Thus the goal of this research project is to study human LVAD patients to determine the impact of artificial pulsatility in CF physiology on microvascular and endothelial function and its association with cardiac and peripheral organ function
Our interest lies in the impact of continuous flow hemodynamics on endothelial function and the cardiac and end-organ responses to this novel therapy Basal homeostatic properties of healthy endothelium are in part based on the effects of hemodynamic forces such as hydrostatic pressure cyclic stretch and fluid shear stress which occur as a consequence of blood pressure and pulsatile blood flow in the vasculature Under ambient conditions these forces are generally atheroprotective and increase the expression of nitric oxide synthase eNOS to generate nitric oxide NO decrease reactive oxidative species ROS and oxidative stress decrease expression of proinflammatory adhesion molecules and maintain an antithrombotic surface Increases in shear stress stimulate compensatory expansion of the vessels and thereby return shear forces to basal levels Likewise a decrease in shear stress can narrow the lumen of the vessel in an endothelium-dependent manner In essence the vessel remodels itself in response to long-term changes in flow such that the luminal diameter is reshaped to maintain a constant predetermined level of shear stress The capacity of the endothelium to sense shear stress is therefore an important determinant of luminal diameter and overall vessel structure Failure to adapt to pathophysiological stimuli may lead to maladaptive responses that result in seemingly permanent alterations in endothelial phenotype and promote endothelial dysfunction This phenomenon plays an integral role in several cardiovascular disease processes Endothelial dysfunction of both microvascular and conduit arteries is a component of chronic heart failure and correlates with severity of disease Improvement in cardiac function whether via medical therapy or cardiac output augmentation can improve endothelial function and benefit patients through better peripheral vascular reactivity However much of the improvement in endothelial function is thought to be related to the pulsatile laminar flow that occurs in majority of vascular beds With the increasing use of CF pumps it has become clear that the lack of pulsatility adversely affects the endothelium by decreasing vessel wall shear stress reducing cyclic stretch that affects vascular cell proliferation disrupting endothelium-dependent vasodilation activating extrinsic pathway of thrombosis and heightening vascular inflammation The reintroduction of pulsatility through flow modulation control strategies could help mitigate these device specific issues and help promote endothelial recovery Our knowledge of the impact of these specific advances in LVAD therapy is however limited by the relative youth of the field Thus the goal of this research project is to study human LVAD patients to determine the impact of artificial pulsatility in CF physiology on microvascular and endothelial function and its association with cardiac and peripheral organ function
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None