Baroreflex Activation Therapy for Heart Failure | Clinical Trial - BAT for HFrEF

Mar 16, 2015
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Presenter/Author:
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
CVRx, Inc., Minneapolis, Minnesota
Date Presented:
03/16/2015
Date Published:
03/16/2015
Original Posted Date:
03/16/2015
References

Description:

The goal of the trial was to compare the safety and efficacy of BAT in patients with chronic systolic heart failure (HF).

Contribution to the Literature: This pilot study suggests that baroreflex activation therapy may provide symptomatic benefit in patients with chronic systolic HF.


Study Design

Patients were randomized in a 1:1 fashion to either BAT implantation in addition to optimal medical therapy  (n = 76) or optimal medical therapy (n = 70).

Following BAT implantation, it was gradually uptitrated based on hazard ratio and blood pressure response.

Patient population:

  • Total number of enrollees: 146
  • Duration of follow-up: 6 months
  • Mean patient age: 65 years
  • Percentage female: 14%
  • Percentage diabetics: 35%

Other salient features/characteristics:

  • 6-minute walk distance: ~303 m
  • Left ventricular ejection fraction (LVEF): 25%
  • Implantable cardioverter-defibrillator (ICD): 86%
  • Cardiac resynchronization therapy (CRT): 32%
  • Medications: ACE inhibitor/ARB (79%), beta-blockers (86%), mineralocorticoid receptor antagonist (55%)

Inclusion criteria:

  • NYHA class III HF
  • LVEF ≤35%
  • Patients were required to be treated with chronic stable guideline-directed medical therapy
  • Resting heart rate between 60 bpm and 100 bpm
  • Systolic blood pressure of at least 100 mm Hg
  • Estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2
  • Demonstrated impairment in functional capacity as evidenced by a 6-minute walk distance between 150 and 450 m
  • Suitable surgical candidates for BAT device implantation
  • Bilateral carotid bifurcations below the level of the mandible
  • Freedom from plaques or atherosclerosis reducing the linear diameter of the internal or distal common carotid arteries by 50% or greater

Exclusion criteria:

  • Patients who had experienced NYHA class IV HF symptoms with acute pulmonary edema within 45 days of randomization
  • Myocardial infarction, unstable angina, syncope, cerebrovascular accident, or aborted sudden cardiac death (including appropriate ICD therapies) during the 3 months prior to randomization
  • Pacemaker or ICD device implanted within 90 days of enrollment
  • CRT device within 6 months of enrollment or were anticipated to receive one within 90 days
  • Known or suspected baroreflex failure or autonomic neuropathy
  • Prior surgery, radiation, or endovascular stent placement in the carotid sinus region that limited the ability to place the carotid sinus lead
  • Current treatment with inotropes
  • Life expectancy <1 year
  • Body mass index >40 kg/m2
  • Symptomatic uncontrolled bradyarrhythmias
  • Previous or current consideration of solid organ transplant
  • Asthma requiring chronic medication
  • Severe chronic obstructive pulmonary disease or restrictive lung disease
  • Noncardiovascular conditions interfering with 6-minute walk distance assessment
  • Active malignancy
  • Noncompliance with medical therapy

Principal Findings:

The primary safety outcome, freedom from major adverse neurological and cardiovascular events in the BAT arm, was 97.2%. This included hematomas in two patients. On per-protocol analysis, the primary efficacy outcomes for BAT vs. control were: improved NYHA class (55% vs. 24%, p = 0.002), 6-minute walk distance (59.6 vs. 1.5 m, p = 0.004), Minnesota Living with HF quality of life (-17.4 vs. 2.1, p < 0.001).

Secondary outcomes:

  • Change in number of HF hospitalization days per year pre vs. post enrollment (-6.3 vs. 0.08, p ≤ 0.05)
  • Change in NT-pro-BNP (-69 vs. 129.5, p = 0.02)
  • Systolic blood pressure was higher in the BAT group compared with baseline, but not in the control group

Interpretation:

The results of this pilot trial indicate that among patients with chronic systolic HF, the addition of BAT to optimal medical therapy provides modest symptomatic benefit at 6 months, compared with optimal medical therapy alone. Larger studies, powered for clinical outcomes, are awaited.

BAT is thought to be beneficial in CHF by reducing sympathetic activity and increasing parasympathetic activity via activation of the carotid baroreceptors. In an earlier trial, the utility of BAT was assessed in patients with resistant hypertension using sham controls. The overall results were negative. Since the majority of efficacy endpoints in this trial were subjective, performance or knowledge bias in the treatment arm could explain some or all of the findings. Future trials will also need to consider sham controls for this reason.

References:

Abraham WT, Zile MR, Weaver F, et al. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction. JACC Heart Fail 2015;Mar 16:[Epub ahead of print].

Presented by Dr. William T. Abraham at ACC.15, San Diego, CA, March 16, 2015.

Keywords: ACC Annual Scientific Session, Heart Failure, Heart Failure, Systolic, Hospitalization, Cardiomyopathies, Disease Progression, Defibrillators, Implantable, Cardiac Resynchronization Therapy


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