Baroreflex Activation Therapy in Left Ventricular Assist Device Patients Study (BAT-VAD)

Baroreflex Activation Therapy in Left Ventricular Assist Device Patients Study (BAT-VAD Study)

This study will involve LVAD patients who have already received a clinically-indicated BAT (BAROSTIM) device. After recovery from LVAD implant, we will investigate the effects of BAT in a double-blind cross-over study design.

Study Overview

• Status: Recruiting
• Conditions: Congestive Heart Failure
• Intervention / Treatment: Device: Baroreflex Activation Therapy (BAT)

Detailed Description

Left ventricular assist devices (LVADs) provide a meaningful therapeutic option for patients with end-stage systolic heart failure who cannot receive cardiac transplantation. For these patients, LVADs have been shown to improve mortality, functional capacity, and quality of life [1-3]. With ever-improving technological and procedural advances, the number of LVAD implantations for patients with end-stage cardiomyopathy as bridge to transplant, recovery, or even as destination therapy continues to rise [4]. Despite the short term clinical benefits of LVAD support, studies show that deleterious neurohormonal activation does not abate after LVAD implantation and that left ventricular scarring (or fibrosis) does not regress and may worsen. Similarly, the prevalence of myocardial recovery with LVAD support has been dismally low with <1% of patients recovering to the point where their LVAD can be safely explanted. Given that the majority of patients undergoing LVAD are now doing so with a destination therapy designation, and that the median estimated survival time on LVAD support ranges from 4-6 years, the importance of therapies to maximize chances for myocardial recovery while LVAD supported is evident.

The pathophysiologic reasons underlying the lack of abrogation of sympathetic and neurohormonal signaling with LVAD support, even in the face of adequate hemodynamic support, may center around the non-pulsatile nature of the device. Markham and Levine described sympathetic nerve activity in both pulsatile and nonpuslatile LVAD patients in 2013, demonstrating that patients with nonpulsatile devices had markedly elevated muscle sympathetic nerve activity, though pulsatile LVAD patients and normal controls had similar sympathetic activity. In a sequence of experiments, the authors demonstrated that this was at least partly due to baroreceptor unloading in the nonpulsatile patients. Further studies have demonstrated that plasma norepinephrine levels remain elevated after VAD implant, as do neurohormones in the renin-angiotensin-aldosterone axis. Sympathetic neurohormone levels have been shown to correlate with clinical response to LVAD therapy (defined by significant improvement in quality of life determined by the KCCQ), with reduced B-adrenergic receptor kinase-1 and DHPG levels differentiating those with better clinical response. Further, pathologic studies pre- and post-LVAD have demonstrated an acceleration of deleterious myocardial fibrosis during LVAD support, potentially driven by sympathetic and/or RAAS signaling pathways.

As demonstrated in preclinical studies and the clinical BeAT-HF trial, autonomic modulation with baroreflex activation therapy (BAT) with the BAROSTIM NEO system reduced sympathetic signaling, leading to increased NT-proBNP, 6-minute hall walk distance (6MHW), and improved quality of life in patients with chronic systolic heart failure.

However, the role of BAT in the unique physiologic LVAD-supported state has not be characterized. Given the concerns that LVAD support by augment sympathetic and thereby RAAS signaling, and that BAT may abrogate those deleterious pathways, we propose to study the clinical and neurohormonal effects of BAT in LVAD supported patients.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Renee L Baxley, BS; Phone Number: 843-792-1105; Email: baxleyr@musc.edu
      • Principal Investigator: Brian A Houston, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years
• LVAD patient > 3 months post implant
• Existing BAT device

Exclusion Criteria:

• Presence of cardiogenic shock, respiratory failure, hypotension or unstable heart failure
• Bradycardia (resting HR <60 beats/minute)
• Presence of suspected pump thrombosis at the time of enrollment
• Presence of any significant ventricular arrhythmias at the time of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: control (BAT off); Baroreflex activation therapy turned off for three months	Device: Baroreflex Activation Therapy (BAT); activation of BAROSTIM NEO system that affects autonomic modulation with BAT therapy.
Experimental: treatment (BAT on); Baroreflex activation therapy turned on for three months	Device: Baroreflex Activation Therapy (BAT); activation of BAROSTIM NEO system that affects autonomic modulation with BAT therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Minute Hall Walk	change in distance walked during 6 Minute Hall Walk	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minnesota Living with Heart Failure Questionnaire	quality of life questionnaire	3 months, 6 months
Change in LVAD system monitor reported flow	Liters/minute	3 months, 6 months
Cardiac 123-mIBG scan	Heart to mediastinum uptake ratio; Rate of 123-mIBG washout	3 months, 6 months
Change in left ventricular size on transthoracic echocardiogram	Centimeters	3 months, 6 months
Change in aortic valve opening frequency on transthoracic echocardiogram	Valve opening per beat	3 months, 6 months
Change in mitral valve regurgitation severity on transthoracic echocardiogram	None, mild, moderate, severe	3 months, 6 months
Change in right ventricular size on transthoracic echocardiogram	Centimeters	3 months, 6 months
Change in Serum catecholamines	pg/mL	3 months, 6 months
Change in Serum norepinephrine	pg/mL	3 months, 6 months
Change in serum renin	ng/mL	3 months, 6 months
Change in serum aldosterone	ng/dL	3 months, 6 months
Change in serum angiotensin	U/L	3 months, 6 months
Change in serum BNP	pg/mL	3 months, 6 months

Collaborators and Investigators

• Sponsor: Brian Houston
• Collaborators: CVRx, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): April 25, 2026
• Study Completion (Estimated): April 25, 2027

Study Registration Dates

• First Submitted: July 21, 2023
• First Submitted That Met QC Criteria: January 5, 2024
• First Posted (Estimated): January 8, 2024

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Ventricular Assist Device; Baroreflex activation therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: Pro00115552

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: Yes
• product manufactured in and exported from the U.S.: No