Alleviate-HF-1 Study
Alleviate-HF-1 Study
Patients with heart failure and preserved left ventricular ejection fraction (HFpEF, EF ≥
 50%) or mid-range left ventricular ejection fraction (HFmrEF, 40% < EF < 50%) with mild to
 moderate functional limitation will be evaluated for treatment via creation of a no-implant
 interatrial shunt using clinical, echocardiographic, and invasive hemodynamic data.
Inclusion Criteria:

 1. Documented history of NYHA Class II, Class III or ambulatory Class IV at the screening
 visit.

 2. History of at least one hospitalization for treatment of heart failure within the past
 12 months.

 3. LVEF greater than 40% as measured by the study-specific transthoracic
 echocardiography.

 4. Echocardiographic evidence of diastolic dysfunction documented by one or more of the
 following as measured by the study-specific transthoracic echocardiography protocol
 performed during screening:

 -  LA diameter greater than 4 cm

 -  LA volume index greater than 28 mL

 -  Lateral e' less than 10 cm/s

 -  Septal e' less than 8 cm/s

 -  Lateral E/e' greater than 10

 -  Septal E/e' greater than 15

 5. 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 greater than or equa. to 25
 mmHg AND (2) PCWP greater than RAP by greater than or equal to 5 mmHg, OR greater than or
 equal to 10 mmHg increase of end-expiratory PCWP at peak supine cycle ergometer exercise
 compared to resting PCWP AND PCWP greater than RAP by greater than or equal to 5 mmHg.

 Exclusion Criteria:

 1. 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.

 2. 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.

 3. . 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%.

 4. Documented as currently requiring dialysis or estimated GFR less than 25ml/min/1.73m2

 5. 6-minute walk distance less than 50 m or greater than 450 m performed during
 screening.

 6. Documented atrial fibrillation with ventricular rate greater than 100 BPM at
 screening.

 7. 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%

 8. Presence of pulmonary hypertension with PASP greater than or equal to 70 mmHg OR PVR
 greater than 4 Wood units.

 9. Presence of anatomic anomaly that precludes creation of interatrial shunt (including
 patent foramen ovale, atrial septal defect, target septal thickness greater than 3 mm)

 10. SBP greater than 170 mmHg at screening.

 11. Documented left ventricular end diastolic diameter greater than 6 cm.