Alleviate-HF-2 Study

Inclusion criteria

• NYHA Class II at screening with a prior history of greater than NYHA Class II, OR NYHA Class III at screening, OR ambulatory Class IV at screening: with documented medical history of heart failure for at least 6 months prior to the screening visit.
• Medical history within the past 12 months of at least one hospitalization with heart failure as the primary or secondary diagnosis OR treatment with IV diuretics for heart failure..
• LVEF (by Echo) > 40% as measured by the study-specific transthoracic echocardiography.
• Echocardiographic evidence of diastolic dysfunction documented by one or more of the following as measured by the study-specific transthoracic echocardiography protocol:

• LA diameter > 4cm
• LA volume index >28 mL
• Lateral e' <10 cm/s
• Septal e' <8 cm/s
• Lateral E/e' >10
• Septal E/e' >15
• As measured by the study-specific exercise hemodynamic right heart catheterization protocol performed during screening: Elevated left atrial pressure WITH a gradient compared to right atrial pressure (RAP) documented by: (1) end-expiratory PCWP at peak supine cycle ergometer exercise ≥ 25mmHg AND (2) PCWP greater than RAP by ≥ 5 mmHg, OR (1) ≥ 10 mmHg increase of end-expiratory PCWP at peak supine cycle ergometer exercise compared to resting PCWP AND (2) PCWP greater than RAP by ≥ 5 mmHg. Patients must also have PCWP greater than RAP by ≥ 5 mmHg at rest.

Exclusion criteria

• Presence of advanced heart failure defined as one or more of the following:

• ACC/AHA/ESC Stage D heart failure, non-ambulatory NYHA Class IV HF.
• Cardiac index less than 2.0 L/min/m2.
• Patient is on the cardiac transplant waiting list.
• Inotropic infusion (continuous or intermittent) for EF less than 40% within the past 6 months.
• Presence of moderate or worse valve disease, defined as one or more of the following:

• Moderate or worse mitral valve regurgitation or moderate or worse mitral stenosis.
• Moderate or worse tricuspid valve regurgitation.
• Moderate or worse aortic valve disease defined as moderate or worse AS or AI.
• . Presence of chronic pulmonary disease defined by one or more of the following:

• Requirement for continuous home oxygen use.
• Hospitalization within the past 12 months for treatment of pulmonary disease.
• Significant chronic pulmonary disease defined as FEV1 less than 50%.
• Documented as currently requiring dialysis or estimated GFR less than 25ml/min/1.73m2
• 6-minute walk distance less than 50 m or greater than 450 m performed during screening.
• Documented atrial fibrillation with ventricular rate greater than 100 BPM at screening.
• Presence of moderate or worse right heart dysfunction OR RV dysfunction defined as TAPSE less than 14 mm or RVFAC less than or equal to 30%
• Presence of pulmonary hypertension with PASP greater than or equal to 70 mmHg OR PVR greater than 4 Wood units.
• Presence of anatomic anomaly that precludes creation of interatrial shunt (including patent foramen ovale, atrial septal defect, target septal thickness greater than 3 mm)
• SBP greater than 170 mmHg at screening.
• Documented left ventricular end diastolic diameter greater than 6 cm.