Neuromodulation to Treat Patients With Heart Failure With Preserved Ejection Fraction

University of Oklahoma (OU)

Status: Completed

Conditions: Heart Failure With Normal Ejection Fraction

Treatments: Device: low level transcutaneous vagus nerve stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT03327649

8251

Details and patient eligibility

About

Heart failure with preserved ejection fraction (HFpEF) is a leading cause of mortality in the elderly. Outcomes of patients with HFpEF are poor and so far, no treatment has been shown to decrease morbidity or mortality. Recent animal and human studies suggest that a systemic proinflammatory state, produced by comorbidities, including aging, plays a central role in the development of HFpEF, supporting the notion that attenuating the proinflammatory state is an attractive therapeutic target for HFpEF. We have previously shown that low-level transcutaneous electrical stimulation of the vagus nerve (tVNS) suppresses inflammation in patients with atrial fibrillation. The overall objective of this proposal is to examine the effects of tVNS on diastolic dysfunction, exercise capacity and inflammation in patients with HFpEF. Our specific aims include: 1. To examine the effect of intermittent (1 hour daily for 3 months) tVNS on diastolic dysfunction and exercise capacity, relative to sham stimulation, in patients with HFpEF and 2. To examine the effect of intermittent (1 hour daily for 3 months) LLTS on inflammatory cytokines relative to sham stimulation, in patients with HFpEF. The proposed proof-of-concept studies will provide the basis for the design of further human studies using LLTS among populations with HFpEF. In light of the increasing number of elderly patients with HFpEF and the poor success of the currently available treatment options, an alternative and novel approach such as tVNS has the potential to impact clinical practice and improve health outcomes among a large number of patients. It is anticipated that these investigations will contribute to the broader understanding of the role of inflammation in the pathogenesis of HFpEF and how its inhibition can be used to provide therapeutic effects. Moreover, it is anticipated that a better understanding of how modulation of inflammation affects one of the hallmarks of HFpEF, diastolic dysfunction, will lead to the development of novel pharmacological and non-pharmacological approaches to treat this disease.

Enrollment: 52 patients

Sex: All

Ages: 21 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• HFpEF, defined as signs and symptoms of heart failure, LV ejection fraction ≥50%, brain natriuretic peptide ≥35pg/mL and echocardiographic evidence of diastolic dysfunction (left atrial volume index ≥34mL/m2, mitral E-wave velocity/mitral annular velocity ratio [E/e']≥13 and e'<9cm/s) plus 2 of the following 4 comorbidities:

  • age ≥ 65,
  • diabetes,
  • hypertension and
  • obesity, defined as body mass index ≥30kg/m2

Exclusion criteria

• LV ejection fraction <40%
• significant valvular disorder (i.e., prosthetic valve or hemodynamically significant valvular diseases)
• recent (<6 months) stroke, myocardial infarction or hospitalization for heart failure
• severe heart failure (class III or IV)
• end stage kidney disease
• recurrent vasovagal syncope
• history of vagotomy
• pregnancy
• sick sinus syndrome and 2nd or 3rd degree AV block (without a pacemaker).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

52 participants in 2 patient groups

Sham control

Sham Comparator group

Description:

Patients will receive 1 hour of sham transcutaneous low level vagal stimulation daily for 3 months

Treatment:

Device: low level transcutaneous vagus nerve stimulation

Active treatment

Experimental group

Description:

Patients will receive 1 hour of active transcutaneous low level vagal stimulation daily for 3 months

Treatment:

Device: low level transcutaneous vagus nerve stimulation