LVAD Conditioning for Cardiac Recovery

NCT ID: NCT03238690

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-23
• Study Completion Date: 2028-06-30

Brief Summary

The purpose of this study is to investigate the potential recovery of heart function in end-stage heart failure patients supported with a Left Ventricular Assist Device (LVAD) through applying a myocardial conditioning protocol. During myocardial conditioning, LVAD speed is reduced gradually in order to increase the work load of the heart. Multiple previous studies have shown that interventions like this may improve heart function and give patients the opportunity for a better quality of life.

Detailed Description

Heart failure can be caused by various disorders, such as myocardial infarction, hypertension, viral infection, exposure to toxins, chemotherapy, or genetically transmitted muscular diseases. Regardless of the etiology, these disorders initiate ventricular remodeling, an adaptive, compensatory process which becomes progressively maladaptive and the cause of functional and clinical deterioration, eventually leading to heart failure. Local and systemic compensatory responses that initially allow surviving muscle to maintain hemodynamic function continue over time and due to this persistent compensatory over-activity the initially unaffected myocardium becomes dysfunctional. These compensatory responses to an abnormal cardiac load or myocardial injury involve several pathophysiological adaptations in the cardiac structure at the genetic, molecular, cellular, and tissue levels. Furthermore, left ventricular pressure and volume overload has shown to alter metabolic substrate utilization, decrease mitochondrial function and reduce energy production in the failing heart.

Mechanical circulatory support with LVAD has become a standard bridge to cardiac transplantation, and has also been approved in the United States as permanent (destination) therapy for selected patients presenting with end-stage heart failure. Clinical experience with LVAD support has shown that it can reverse the complex process of chronic left ventricular remodeling to a point where a subset of patients could be weaned from the device after restoration of basic cardiac function. LVAD-induced mechanical unloading of the failing heart leads to reduced mitochondrial density, structure and function, and interventions that enhance mitochondrial biogenesis, function and structure, such as controlled cardiac reloading may enhance LVAD-induced myocardial reverse remodeling and cardiac recovery. This study is designed to investigate gradual reduction in LVAD speed within the range defined by the assist device manufacturer's manual as appropriate for regular clinic use, to determine the effect on reverse remodeling and myocardial recovery in end-stage heart failure patients.

Conditions

Heart Failure

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Controlled Cardiac Reloading

Heart failure patients with recent LVAD implantation after an optimum unloading phase, will undergo controlled cardiac reloading through LVAD speed adjustment reductions in a controlled reloading phase

Group Type: EXPERIMENTAL

Controlled Cardiac Reloading through LVAD Speed Adjustment

Intervention Type: DEVICE

LVAD speed is reduced at a fixed rate according to the particular LVAD device model implanted. LVAD speed reduction adjustments will be performed at visits occurring every 2 - 3 weeks, up to a total of 8 visits. Reduction of LVAD speed will continue until the soonest of: minimum operating setting as recommended in the LVAD Operator's manual is reached; the minimum setting tolerated by the subject is reached; the subject completes 8 visits; or until the subject receives a heart transplant.

Interventions

Controlled Cardiac Reloading through LVAD Speed Adjustment

LVAD speed is reduced at a fixed rate according to the particular LVAD device model implanted. LVAD speed reduction adjustments will be performed at visits occurring every 2 - 3 weeks, up to a total of 8 visits. Reduction of LVAD speed will continue until the soonest of: minimum operating setting as recommended in the LVAD Operator's manual is reached; the minimum setting tolerated by the subject is reached; the subject completes 8 visits; or until the subject receives a heart transplant.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Diagnosed with heart failure undergoing LVAD implantation as a bridge to transplant
• Enrolled in the Effects of Mechanical Unloading on Myocardial Function and Structure study (IRB 30622)

Exclusion Criteria

• Neither the subject nor the subject's representative is willing to provide written consent for participation
• Subjects with adverse events leading to hospitalization during the optimum unloading phase are excluded from participation in the controlled reloading phase

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

STAVROS G DRAKOS

OTHER

Sponsor Role: lead

Responsible Party

STAVROS G DRAKOS

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Stavros Drakos, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

Salt Lake City, Utah, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

John Kirk

Role: CONTACT

john.kirk@hsc.utah.edu

801-585-2944

Facility Contacts

Stavros Drakos, MD

Role: primary

stavros.drakos@hsc.utah.edu

801-585-2340

References

George RS, Sabharwal NK, Webb C, Yacoub MH, Bowles CT, Hedger M, Khaghani A, Birks EJ. Echocardiographic assessment of flow across continuous-flow ventricular assist devices at low speeds. J Heart Lung Transplant. 2010 Nov;29(11):1245-52. doi: 10.1016/j.healun.2010.05.032. Epub 2010 Aug 5.

Reference Type: BACKGROUND

PMID: 20688540 (View on PubMed)

Healy AH, Koliopoulou A, Drakos SG, McKellar SH, Stehlik J, Selzman CH. Patient-controlled conditioning for left ventricular assist device-induced myocardial recovery. Ann Thorac Surg. 2015 May;99(5):1794-6. doi: 10.1016/j.athoracsur.2014.07.058.

Reference Type: BACKGROUND

PMID: 25952209 (View on PubMed)

Frazier OH, Baldwin AC, Demirozu ZT, Segura AM, Hernandez R, Taegtmeyer H, Mallidi H, Cohn WE. Ventricular reconditioning and pump explantation in patients supported by continuous-flow left ventricular assist devices. J Heart Lung Transplant. 2015 Jun;34(6):766-72. doi: 10.1016/j.healun.2014.09.015. Epub 2014 Sep 28.

Reference Type: BACKGROUND

PMID: 25447571 (View on PubMed)

Other Identifiers

IRB_00095106

Identifier Type: -

Identifier Source: org_study_id