RESPONDER-HF Trial

Inclusion Criteria:

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

2. Symptoms of HF requiring current treatment with diuretics if tolerated for ≥ 30days AND

3. New York Heart Association (NYHA) class II; OR NYHA class III, or ambulatoryNYHA class IV symptoms; AND

4. ≥ 1 HF hospital admission (with HF as the primary, or secondary diagnosis); ortreatment with intravenous (IV) diuretics; or intensification of oral diuresiswithin the 12 months prior to study entry; OR an NT-proB-type NatriureticPeptide (NT-pro BNP) value > 150 pg/ml in normal sinus rhythm, > 450 pg/ml inatrial fibrillation, or a brain natriuretic peptide (BNP) value > 50 pg/ml innormal sinus rhythm, > 150 pg/ml in atrial fibrillation within the past 6months

5. Ongoing stable guideline-directed medical therapy (GDMT) HF management andmanagement of comorbidities according to the 2022 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of HeartFailure. Stable management includes a minimum period of 4 weeks post-hospitalizationfor any cause, including treatment with IV diuretics

6. Site determined echocardiographic LV ejection fraction ≥ 40% within the past 6months, without documented ejection fraction < 30% in the 5 years prior.

7. Site determined echocardiographic evidence of diastolic dysfunction documented byone or more of the following:

8. Left Atrial (LA) diameter > 4 cm; or

9. Diastolic LA volume > 50 or LA volume index > 28 ml/m2 or

10. Lateral e' < 10 cm/s; or

11. e' < 8 cm/s; or

12. Site determined elevated pulmonary capillary wedge pressure (PCWP) with a gradientcompared to right atrial pressure (RAP) documented by end-expiratory PCWP duringsupine ergometer exercise ≥ 25 millimeters of mercury (mm Hg), and greater than RAPby ≥ 5 mm Hg.

13. Resting RAP ≤ 14 mmHg

14. Site determined hemodynamic evidence of peak exercise pulmonary vascular resistance (PVR) < 1.75 Wood units

15. Age ≥ 40 years old

16. Participant has been informed of the nature of the study, agrees to its provisionsand has provided written informed consent, approved by the Institutional ReviewBoard (IRB) or Ethics Committee (EC)

17. Participant is willing to comply with clinical investigation procedures and agreesto return for all required follow-up visits, tests, and exams

18. Transseptal catheterization and femoral vein access to the right atrium isdetermined to be feasible by site interventional cardiology investigator.

Exclusion Criteria:

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

2. ACC/AHA/European Society of Cardiology (ESC) Stage D heart failure,non-ambulatory NYHA Class IV HF

3. Cardiac index < 2.0 L/min/m2

4. Inotropic infusion (continuous or intermittent) for EF < 40% within the past 6months

5. Patient is on the cardiac transplant waiting list.

6. Inability to perform 6-minute walk test (distance < 50 meters), OR 6-minute walktest > 600m

7. The patient has verified that the ability to walk 6 minutes is limited primarily byjoint, foot, leg, hip or back pain; unsteadiness or dizziness or lifestyle (and notby shortness of breath and/or fatigue and/or chest pain)

8. Right ventricular dysfunction, assessed by the site cardiologist and defined as oneor more of the following:

9. More than mild right ventricular (RV) dysfunction as estimated by transthoracicechocardiogram (TTE); OR

10. TAPSE < 1.4 cm; OR

11. Right ventricular (RV) size ≥ left ventricular (LV) size as estimated by TTE;OR

12. Ultrasound or clinical evidence of congestive hepatopathy; OR

13. Evidence of RV dysfunction defined by TTE as an RV fractional area change < 35%.

14. Any implanted cardiac rhythm device

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

16. Mitral valve disease grade ≥ 3+ mitral regurgitation (MR) or > mild MitralStenosis (MS); OR

17. Tricuspid valve (TR) regurgitation grade ≥ 2+ TR; OR

18. Aortic valve disease ≥ 2+ aortic regurgitation (AR) or > moderate aorticstenosis (AS)

19. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation

20. Participants with existing or surgically closed (with a patch) atrial septaldefects. Participants with a patent foramen ovale (PFO), who meet PCWP criteriadespite the PFO, are not excluded

21. Myocardial Infarction (MI) and/or percutaneous cardiac intervention within past 3months; Coronary Artery Bypass Graft (CABG) surgery in past 3 months or any plannedcardiac interventions in the 3 months following enrollment.

22. Known clinically significant un-revascularized coronary artery disease, defined as:coronary artery stenosis with angina or other evidence of ongoing active coronaryischemia

23. Known clinically significant untreated carotid artery stenosis likely to requireintervention

24. Atrial fibrillation with resting heart rate (HR) > 100 beats-per-minute (BPM)

25. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictivepericarditis, cardiac amyloidosis or infiltrative cardiomyopathy (e.g.hemochromatosis, sarcoidosis)

26. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), orpulmonary emboli within the past 6 months

27. Participant is contraindicated to receive either dual antiplatelet therapy, or anoral anticoagulant; or has a documented coagulopathy

28. Anemia with Hemoglobin < 10 g/dl

29. Chronic pulmonary disease requiring continuous home oxygen, OR significant chronicpulmonary disease defined as forced expiratory volume (FEV)1 <1Liter

30. Resting arterial oxygen saturation < 95% on room air, <93% when residing at highaltitude

31. Currently requiring dialysis; or estimated glomerular filtration rate eGFR < 25ml/min/1.73 m2 by chronic kidney disease (CKD) CKD-Epi equation

32. Systolic blood pressure > 170 mm Hg at screening

33. Significant hepatic impairment defined as 3 times upper limit of normal oftransaminases, total bilirubin, or alkaline phosphatase

34. Participants on significant immunosuppressive treatment or on systemic steroidtreatment

35. Life expectancy less than 12 months for known non-cardiovascular reasons

36. Known hypersensitivity to nickel or titanium

37. Women of childbearing potential

38. Severe obstructive sleep apnea not treated with continuous positive airway pressure (CPAP) or other measures

39. Body Mass Index (BMI) > 45; BMI 40 - 45 is also excluded unless in the opinion ofthe investigator, vascular access can be obtained safely

40. Severe depression and/or anxiety

41. Currently participating in an investigational drug or device study that wouldinterfere with the conduct or results of this study. Note: trials requiring extendedfollow-up for products that were investigational but have since become commerciallyavailable are not considered investigational

42. In the opinion of the investigator, the Participant is not an appropriate candidatefor the study.