Endothelial Function in Mechanical Circulatory Support

NCT04539093 | Completed

• 1 other identifier: PRO00038133
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure With Reduced Ejection Fraction; Endothelial Dysfunction; LVAD

Keywords

Observational; Pilot study

Outcome Measures

Primary Outcomes (2)

• Evaluation of endothelial function

  Measurement of blood nitric oxide levels will be used to evaluate vascular endothelial function. Flow-mediated dilation technique will then be used as a barometer of nitric oxide availability. The concentration of nitric oxide levels and degree of flow-mediated dilation would correlate with endothelial function.

  9 months

• Evaluation of microvascular function

  Contrast enhanced ultrasound of the peripheral skeletal muscle of lower extremities will be used to evaluate microvascular function. Blood flow quantified using the ultrasound images would correlated with microvascular function.

  9 months

Secondary Outcomes (5)

• Functional outcomes - Quality of Life

  9 months

• Functional outcomes - Mobility

  9 months

• Functional outcomes - Handgrip

  9 months

• Functional outcomes - Lower extremity strength

  9 months

• Functional outcomes - Ventilation and gas exchange

  9 months

Study Arms (1)

End-stage heart failure patients requiring lvad support

Patients with end-stage heart failure with reduced ejection fraction, requiring mechanical circulatory support.

Other: Exposure of interest - Use of left ventricular assist device (LVAD)

Interventions

Exposure of interest - Use of left ventricular assist device (LVAD) OTHER

Mechanical circulatory support devices such as left ventricular assist device is used as a treatment option for patients with end-stage heart failure.

End-stage heart failure patients requiring lvad support

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

End-stage heart failure patients at an academic medical center who are scheduled for LVAD implantation, will be screened for their candidacy in this study.

You may qualify if:

• Patients over the age of 18 years, deemed to be candidates for LVAD implantation. All ethnicities will be included in this study.

You may not qualify if:

• Age \< 18 years or \> 85 years.
• Presence of intra-cardiac shunt - safety concern for use of Echo contrast.
• Patient requiring temporary MCS - high acuity; may not be feasible to perform baseline assessment.
• Severe peripheral vascular disease - potential confounding bias during ultrasound assessment.
• Skeletal muscle disorder - not feasible to assess functional outcomes.
• Underlying/genetic vascular disease, i.e. vasculitis - potential for confounding bias during ultrasound assessment.
• Pregnant women - potential risk to fetus.
• Non-English Speaking.
• Active alcohol or illicit substance use.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (25)

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  PMID: 28476564 BACKGROUND

• Bristow MR, Kao DP, Breathett KK, Altman NL, Gorcsan J 3rd, Gill EA, Lowes BD, Gilbert EM, Quaife RA, Mann DL. Structural and Functional Phenotyping of the Failing Heart: Is the Left Ventricular Ejection Fraction Obsolete? JACC Heart Fail. 2017 Nov;5(11):772-781. doi: 10.1016/j.jchf.2017.09.009.

  PMID: 29096787 BACKGROUND

• Zimpfer D, Strueber M, Aigner P, Schmitto JD, Fiane AE, Larbalestier R, Tsui S, Jansz P, Simon A, Schueler S, Moscato F, Schima H. Evaluation of the HeartWare ventricular assist device Lavare cycle in a particle image velocimetry model and in clinical practice. Eur J Cardiothorac Surg. 2016 Nov;50(5):839-848. doi: 10.1093/ejcts/ezw232. Epub 2016 Sep 7.

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• Moazami N, Dembitsky WP, Adamson R, Steffen RJ, Soltesz EG, Starling RC, Fukamachi K. Does pulsatility matter in the era of continuous-flow blood pumps? J Heart Lung Transplant. 2015 Aug;34(8):999-1004. doi: 10.1016/j.healun.2014.09.012. Epub 2014 Sep 28.

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• Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2015 Nov 13;4(11):e002270. doi: 10.1161/JAHA.115.002270.

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• Ising MS, Sobieski MA, Slaughter MS, Koenig SC, Giridharan GA. Feasibility of Pump Speed Modulation for Restoring Vascular Pulsatility with Rotary Blood Pumps. ASAIO J. 2015 Sep-Oct;61(5):526-32. doi: 10.1097/MAT.0000000000000262.

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• Symons JD, Deeter L, Deeter N, Bonn T, Cho JM, Ferrin P, McCreath L, Diakos NA, Taleb I, Alharethi R, McKellar S, Wever-Pinzon O, Navankasattusas S, Selzman CH, Fang JC, Drakos SG. Effect of Continuous-Flow Left Ventricular Assist Device Support on Coronary Artery Endothelial Function in Ischemic and Nonischemic Cardiomyopathy. Circ Heart Fail. 2019 Aug;12(8):e006085. doi: 10.1161/CIRCHEARTFAILURE.119.006085. Epub 2019 Aug 19.

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Biospecimen

Retention: NONE RETAINED

Urine specimen - 1 sample per subject taken over a period of 1 day for urine pregnancy test. Up to a total of 60 (20 x 3 visits) samples for the duration of the project. Blood specimen - 1 sample per subject taken over a period of 1 day for measurement of blood nitric oxide levels. Up to a total of 60 (20 x 3 visits) samples for the duration of the project.

Study Officials

• Nicole L Lohr, MD PhD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: September 4, 2020
• Study Start: January 1, 2022
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: October 23, 2023

Record last verified: 2023-10

Locations

US (1)