Synchronized diaphragmatic stimulation for symptomatic heart failure

RECOVER-HF - RandomizEd, Multi-Center, Double-Blinded Study of SynchrOnized Diaphragmatic Stimulation (SDS) for ImproVEment of Symptomatic Reduced Ejection Fraction Heart Failure

This study will test whether a small implanted device that delivers timed diaphragmatic stimulation can help people with heart failure with reduced ejection fraction (LVEF ≤40%) who remain symptomatic on guideline medical therapy.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 270 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: VisCardia Inc. (Industry-sponsored)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06552637 on ClinicalTrials.gov

What this trial studies

Synchronized diaphragmatic stimulation (SDS) uses an implanted VisONE System to rhythmically modulate intrathoracic pressure in time with the cardiac cycle to potentially improve cardiac filling and performance. All enrolled participants receive the VisONE implant, and two weeks after implantation they are randomized 1:1 in a double-blind fashion to active SDS or inactive (sham) programming while continuing guideline-directed medical therapy. Outcomes include safety and measures of symptoms, exercise capacity, biomarkers, and cardiac function with scheduled follow-up visits, including assessment at six months. The trial targets patients with NYHA class II–III heart failure, LVEF ≤40%, and QRS duration ≤130 ms who have not improved sufficiently on medical therapy.

Who should consider this trial

Good fit: Ideal candidates are adults with symptomatic HFrEF (NYHA II–III), LVEF ≤40%, QRS ≤130 ms, and who are on appropriate guideline-directed medical therapy without recent major cardiac events or uncontrolled arrhythmias.

Not a fit: Patients with very high or very low baseline exercise capacity (6MWT >500 m or <200 m), recent unstable cardiac events, uncontrolled arrhythmias, need for inotropic therapy, severe renal or hepatic dysfunction, or other listed exclusions are unlikely to benefit or are ineligible for this protocol.

Why it matters

Potential benefit: If successful, the therapy could reduce symptoms and improve exercise tolerance and cardiac performance for a subset of patients with HFrEF who remain symptomatic despite optimal medical therapy.

How similar studies have performed: Early pilot and feasibility work with synchronized diaphragmatic stimulation has suggested physiological and symptomatic improvements, but randomized, blinded data remain limited and this approach is relatively novel.

Eligibility criteria

Inclusion Criteria:

* NYHA classes II/III on optimal Guideline Directed Medical Therapy (GDMT)
* QRS duration ≤ 130 ms
* EF≤ 40%

Exclusion Criteria:

* Baseline 6 minute walk test \> 500 meters or \< 200 meters
* NT-proBNP\< 250 if on loop diuretics, or NT-proBNP \< 500 if not on loop diuretics
* Supine resting heart rate \> 140 bpm
* Systolic blood pressure \< 80 mmHg or \> 170 mmHg
* Serum creatinine \> 2.5 mg/dL
* Serum hepatic function 3x ULN
* Any of the following within the previous 3 months: unstable angina, AMI, CABG, PTCA, CVA/TIA, persistent AF (\> 24 hours), symptomatic NSVT or DCCV
* Any inotropic drug treatment within the previous 3 months
* Bradycardia (heart rate \< 50 beats/min), atrial arrhythmias with rates \> 100 beats/min, sustained ventricular tachycardia or frequent ventricular ectopy \>10% present during screening
* Significant uncontrolled symptomatic bradyarrhythmia, atrial fibrillation, unstable ventricular arrhythmias or frequent ventricular ectopy \> 10% documented within the previous 3 months
* Reversible non-ischemic cardiomyopathy
* Valvular disease requiring intervention within the next 12 months or presence of significant valve disease as determined by the site cardiologist as:

  1. Greater than mild mitral valve stenosis
  2. Greater than moderate mitral valve regurgitation
  3. Greater than mild tricuspid valve stenosis
  4. Greater than moderate-severe tricuspid valve regurgitation
  5. Greater than moderate aortic stenosis
  6. Greater than moderate aortic regurgitation
  7. Greater than mild-moderate pulmonic stenosis
  8. Greater than moderate pulmonic regurgitation
* Severe primary pulmonary disease, including pulmonary arterial hypertension. PAP sys \>70 mmHg at rest
* Severe COPD, other respiratory or lung diseases where FEV \< 50%
* Presence of more than small pleural effusion or history of pleural drainage within the previous 6 months
* Known history of diaphragmatic paralysis or suspicion confirmed by unilateral or bilateral elevation of the diaphragm on chest x-ray
* Pericardial disease
* Diabetic neuropathy
* Existing diaphragmatic stimulation for respiration assist
* Present LVAD, Baroreflex Activation Therapy, Cardiac Contractility Modulation or interatrial shunt devices; temporary mechanical cardiac assist devices (current or within the previous 3 months); or CRT that is indicated or implanted and functional
* Contraindications to laparoscopic access to the diaphragm, as determined by the implanting physician
* Known intra-abdominal pathology which could increase the risk of laparoscopic access to the diaphragm.
* Previous open laparotomy within 1 year
* Previous thoracic or abdominal organ transplant
* Drug induced immuno-suppression
* Body mass index \> 40
* Enrollment in a concurrent investigation / clinical study
* Having a life expectancy of \<1 year due to any condition
* Pregnant or planning a pregnancy during the study period
* Known allergies to implantable device materials
* History of systemic infection requiring the use of intravenous antibiotics within the previous 3 months

Where this trial is running

Philadelphia, Pennsylvania

• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Lee R Goldberg, MD — University of Pennsylvania
• Study coordinator: Patricia Arand, Ph.D.

Conditions Heart Failure With Reduced Ejection Fraction; Heart Failure; Heart Disease; Synchronized Diaphragmatic Stimulation; Implantable Heart Failure Device Therapy