LVAD Conditioning for Cardiac Recovery

STAVROS G DRAKOS100 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

100

Conditions

Heart Failure

Interventions

Controlled Cardiac Reloading through LVAD Speed AdjustmentDEVICE

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Utah

Salt Lake City, Utah, United States

RECRUITING

Outcomes

Primary Outcomes

Change in Left Ventricular Ejection Fraction (LVEF)

LVEF is measured by echocardiography. The average change in LVEF from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.

Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant

Secondary Outcomes

Change in Left Ventricular End Diastolic Diameter (LVEDD)

LVEDD is measured by echocardiography. The average change in LVEDD from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.

Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant

Change in Left Ventricular End Systolic Diameter (LVESD)

LVESD is measured by echocardiography. The average change in LVESD from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.

Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant

Change in Left Ventricular End Diastolic Volume (LVEDV)

LVEDV is measured by echocardiography. The average change in LVEDV from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.

Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant

Change in Left Ventricular End Systolic Volume (LVESV)

LVESV is measured by echocardiography. The average change in LVESV from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.

Central Contacts

John Kirk

CONTACT

801-585-2944 john.kirk@hsc.utah.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant

Change in heart tissue Glucose 1-phosphate levels

Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Glucose 1-phosphate levels. The average change in Glucose 1-phosphate from baseline to transplant in the study participant arm will be compared to results from an historical control group.