Effect of mechanIcal circulatoRy Support ON Exercise Capacity aMong pAtieNts With Heart Failure (IRONMAN)

Effective Mechanical Circulatory Support on Exercise Capacity in Heart Failure

This study will evaluate how the cardiovascular system interacts with mechanical hearts to provide blood flow to the body during exercise. Two aims are proposed: 1) to determine the impact of a mechanical heart on exercise pressor reflexes in heart failure patients; and 2) to define the primary determinant(s) of exercise capacity in heart failure patients before and after device implantation.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure，Congestive

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Snschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

40 - HF patients with advanced heart failure who are scheduled to undergo LVAD insertion (Advanced Heart Failure)

10 - HF patients with mild heart failure who are not scheduled to undergo LVAD insertion, to serve as first control group (Mild Heart Failure)

10 - Age-matched healthy individuals, with no past medical history, to serve as a second control group (Healthy Controls)

Description

Advanced Heart Failure-

Inclusion Criteria:

• Individuals with severely reduced left ventricular systolic function that are scheduled to undergo LVAD insertion

Exclusion Criteria:

• uncontrolled diabetes with peripheral neuropathy (interferes with acquisition of MSNA signal)
• Individuals with clinical right ventricular failure, defined as moderate-severely reduced RV systolic function on echocardiography, or clinical evidence of RV failure (elevated jugular venous pressures, significant peripheral edema)
• Individuals with moderate-severe preexisting aortic insufficiency, as these patients will typically undergo a Park stitch at time of CF-LVAD insertion to permanently close the aortic valve and prevent worsening aortic insufficiency; and
• Disorders that adversely influence exercise ability (e.g. arthritis, peripheral vascular disease, pulmonary disease)

Mild Heart Failure -

Inclusion Criteria:

• Individuals with medically managed left ventricular systolic function that are NOT scheduled to undergo LVAD insertion
• HF patients with ejection fraction <35-40%

Exclusion Criteria:

• Individuals requiring systemic anticoagulation with vitamin-K antagonists or new/direct oral anticoagulants ("NOAC"/"DOAC")
• Disorders that adversely influence exercise ability (e.g. arthritis, peripheral vascular disease, pulmonary disease)
• History of uncontrolled arrhythmias (e.g. ventricular tachycardia or nonsustained ventricular tachycardia).

Healthy Controls -

Inclusion Criteria:

- Persons without a past medical history of cardiovascular disease or related disease (e.g. hypertension, diabetes, peripheral vascular disease, arrhythmias, stroke/transient ischemic attack) and are not taking any cardiac-related medications (e.g. antihypertensive medications)

Exclusion Criteria:

• Individuals requiring systemic anticoagulation with vitamin-K antagonists or new/direct oral anticoagulants ("NOAC"/"DOAC")
• Disorders that adversely influence exercise ability (e.g. arthritis, peripheral ascular disease).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Advanced Heart Failure; 40 patients with advanced heart failure scheduled to undergo Left Ventricular Assist Device (LVAD) insertion will be recruited for testing. Test subjects will complete testing prior to, and following LVAD implantation.
Healthy controls; 10 age-matched healthy individuals will be recruited to establish normal/reference values.
Mild Heart Failure; A second control group comprised of 10 age-matched individuals will be recruited to establish normal/reference values for individuals with mild, medically managed heart failure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the sympathetic neural response.	The primary outcome will be the difference in the muscle sympathetic neural response (MSNA) to handgrip and post-exercise circulatory arrest (PECA) before and after Continuous-flow left ventricular assist device (CF-LVAD) insertion	4 weeks prior to implantation and 6 months post implantation.
Change in VO2.	The primary outcome will be the change in the VO2 (maximum rate of oxygen consumption) before and after CF-LVAD insertion.	4 weeks prior to implantation and 6 months post implantation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the hemodynamic response.	This outcome will evaluate any difference in the hemodynamic response (heart rate and blood pressure) to handgrip and PECA before and after CF-LVAD	4 weeks prior to implantation and 6 months post implantation.
VO2 relationship and ventilatory threshold (1)	Cardiac output (Qc): VO2 relationship and ventilatory threshold before and after CF-LVAD insertion.	4 weeks prior to implantation and 6 months post implantation.
VO2 relationship and ventilatory threshold (2).	Determinants of Qc after CF-LVAD insertion (ie, contribution from device v. contribution from left ventricle).	4 weeks prior to implantation and 6 months post implantation.
VO2 relationship and ventilatory threshold (3).	Qc, VO2, ventilatory threshold and exercise capacity at increased pump speed.	4 weeks prior to implantation and 6 months post implantation.
VO2 relationship and ventilatory threshold (4).	Bloodflow to the periphery, as measured by transcranial Doppler to assess brain bloodflow during exercise/activity.	4 weeks prior to implantation and 6 months post implantation.
Oxygen uptake and utilization	Cerebral and musculoskeletal oxygen uptake by near-infrared spectroscopy	4 weeks prior to implantation and 6 months post implantation.

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: William K Cornwell, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Sailer C, Edelmann H, Buchanan C, Giro P, Babcock M, Swanson C, Spotts M, Schulte M, Pratt-Cordova A, Coe G, Beindorff M, Page RL 2nd, Ambardekar AV, Pal JD, Kohrt W, Wolfel E, Lawley JS, Tarumi T, Cornwell WK 3rd. Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices. Circ Heart Fail. 2021 Jan;14(1):e007448. doi: 10.1161/CIRCHEARTFAILURE.120.007448. Epub 2021 Jan 19.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2017
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: March 7, 2017
• First Posted (Actual): March 14, 2017

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 16-1635

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No