RESPONDER-HF Trial

Inclusion Criteria:

Chronic symptomatic heart failure (HF) documented by the following:

Symptoms of HF requiring current treatment with diuretics if tolerated for ≥ 30 days AND
New York Heart Association (NYHA) class II; OR NYHA class III, or ambulatory NYHA class IV symptoms; AND
≥ 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV) diuretics; or intensification of oral diuresis within the 12 months prior to study entry; OR an NT-proB-type Natriuretic Peptide (NT-pro BNP) value > 150 pg/ml in normal sinus rhythm, > 450 pg/ml in atrial fibrillation, or a brain natriuretic peptide (BNP) value > 50 pg/ml in normal sinus rhythm, > 150 pg/ml in atrial fibrillation within the past 6 months
Ongoing stable guideline-directed medical therapy (GDMT) HF management and management of comorbidities according to the 2022 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Heart Failure. Stable management includes a minimum period of 4 weeks post-hospitalization for any cause, including treatment with IV diuretics
Site determined echocardiographic LV ejection fraction ≥ 40% within the past 6 months, without documented ejection fraction < 30% in the 5 years prior.

Site determined echocardiographic evidence of diastolic dysfunction documented by one or more of the following:

Left Atrial (LA) diameter > 4 cm; or
Diastolic LA volume > 50 or LA volume index > 28 ml/m2 or
Lateral e' < 10 cm/s; or
e' < 8 cm/s; or
Site determined elevated pulmonary capillary wedge pressure (PCWP) with a gradient compared to right atrial pressure (RAP) documented by end-expiratory PCWP during supine ergometer exercise ≥ 25 millimeters of mercury (mm Hg), and greater than RAP by ≥ 5 mm Hg.
Resting RAP ≤ 14 mmHg
Site determined hemodynamic evidence of peak exercise pulmonary vascular resistance (PVR) < 1.75 Wood units
Age ≥ 40 years old
Participant has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the Institutional Review Board (IRB) or Ethics Committee (EC)
Participant is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams
Transseptal catheterization and femoral vein access to the right atrium is determined to be feasible by site interventional cardiology investigator.

Exclusion Criteria:

Advanced heart failure defined as one or more of the below:

ACC/AHA/European Society of Cardiology (ESC) Stage D heart failure, non-ambulatory NYHA Class IV HF
Cardiac index < 2.0 L/min/m2
Inotropic infusion (continuous or intermittent) for EF < 40% within the past 6 months
Patient is on the cardiac transplant waiting list.
Inability to perform 6-minute walk test (distance < 50 meters), OR 6-minute walk test > 600m
The patient has verified that the ability to walk 6 minutes is limited primarily by joint, foot, leg, hip or back pain; unsteadiness or dizziness or lifestyle (and not by shortness of breath and/or fatigue and/or chest pain)

Right ventricular dysfunction, assessed by the site cardiologist and defined as one or more of the following:

More than mild right ventricular (RV) dysfunction as estimated by transthoracic echocardiogram (TTE); OR
TAPSE < 1.4 cm; OR
Right ventricular (RV) size ≥ left ventricular (LV) size as estimated by TTE; OR
Ultrasound or clinical evidence of congestive hepatopathy; OR
Evidence of RV dysfunction defined by TTE as an RV fractional area change < 35%.
Any implanted cardiac rhythm device

Structural heart repair aortic valve replacement (AVR) or mitral valve replacement (MVR) (surgical or percutaneous) within the past 12 months; planned valve intervention in the next 3 months, or presence of hemodynamically significant valve disease as assessed by the site cardiologist and defined as:

Mitral valve disease grade ≥ 3+ mitral regurgitation (MR) or > mild Mitral Stenosis (MS); OR
Tricuspid valve (TR) regurgitation grade ≥ 2+ TR; OR
Aortic valve disease ≥ 2+ aortic regurgitation (AR) or > moderate aortic stenosis (AS)
Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation
Participants with existing or surgically closed (with a patch) atrial septal defects. Participants with a patent foramen ovale (PFO), who meet PCWP criteria despite the PFO, are not excluded
Myocardial Infarction (MI) and/or percutaneous cardiac intervention within past 3 months; Coronary Artery Bypass Graft (CABG) surgery in past 3 months or any planned cardiac interventions in the 3 months following enrollment.
Known clinically significant un-revascularized coronary artery disease, defined as: coronary artery stenosis with angina or other evidence of ongoing active coronary ischemia
Known clinically significant untreated carotid artery stenosis likely to require intervention
Atrial fibrillation with resting heart rate (HR) > 100 beats-per-minute (BPM)
Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis or infiltrative cardiomyopathy (e.g. hemochromatosis, sarcoidosis)
History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months
Participant is contraindicated to receive either dual antiplatelet therapy, or an oral anticoagulant; or has a documented coagulopathy
Anemia with Hemoglobin < 10 g/dl
Chronic pulmonary disease requiring continuous home oxygen, OR significant chronic pulmonary disease defined as forced expiratory volume (FEV)1 <1Liter
Resting arterial oxygen saturation < 95% on room air, <93% when residing at high altitude
Currently requiring dialysis; or estimated glomerular filtration rate eGFR < 25ml/min/1.73 m2 by chronic kidney disease (CKD) CKD-Epi equation
Systolic blood pressure > 170 mm Hg at screening
Significant hepatic impairment defined as 3 times upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase
Participants on significant immunosuppressive treatment or on systemic steroid treatment
Life expectancy less than 12 months for known non-cardiovascular reasons
Known hypersensitivity to nickel or titanium
Women of childbearing potential
Severe obstructive sleep apnea not treated with continuous positive airway pressure (CPAP) or other measures
Body Mass Index (BMI) > 45; BMI 40 - 45 is also excluded unless in the opinion of the investigator, vascular access can be obtained safely
Severe depression and/or anxiety
Currently participating in an investigational drug or device study that would interfere with the conduct or results of this study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational
In the opinion of the investigator, the Participant is not an appropriate candidate for the study.