ALLEVIATE-HF-HD Study

Inclusion criteria

• NYHA class II if a prior history of > NYHA class II; OR NYHA class III; OR ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening visit.
• Within 12 months of study entry: ≥ 1 HF hospital admission (with HF as the primary or secondary diagnosis); OR treatment with IV diuretics; OR an NT-pro BNP value > 150 pg/ml in normal sinus rhythm, > 450 pg/ml in atrial fibrillation, or a BNP value > 50 pg/ml in normal sinus rhythm, > 150 pg/ml in atrial fibrillation within the past 6 months.
• Site determined echocardiographic LVEF > 25% as measured by the study specific screening transthoracic echo.
• Site determined hemodynamic criteria assessed by the screening supine bicycle exercise right heart catheterization test, including each of the components (a)-(b) below:

a. At rest: i. RAP < 14 mmHg ii. PVR < 3.5 Wood units iii. PAS < 70 mmHg iv. Cardiac Index > 1.9 L/min b. At exercise (25-watts): i. PCWP must have a gradient > 5 mmHg of the RA ii. End-expiratory PCWP ≥ 25 mmHg iii. PVR < 1.8 Wood units [if PVR cannot be obtained (e.g., patient stopped pedaling), TPG < 12 mmHg]

Exclusion criteria

• Presence of advanced heart failure documented in the medical history, defined as one or more of the following:

• ACC/AHA/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.
• Presence of uncorrected valve disease documented in the medical history and/or confirmed by the study-specific TTE protocol performed during screening, defined as one or more of the following:

• Greater than moderate mitral regurgitation
• Greater than moderate mitral stenosis
• Greater than mild tricuspid regurgitation
• Greater than moderate aortic stenosis
• Greater than moderate aortic regurgitation
• Presence of clinically significant untreated carotid artery stenosis documented in the medical history that is likely to require intervention.
• Presence of clinically significant un-revascularized coronary artery disease documented in the medical history that is likely to require intervention, defined as epicardial coronary artery stenosis associated with angina or other evidence of coronary ischemia.
• Presence of hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis or other infiltrative cardiomyopathy such as hemochromatosis or sarcoidosis.
• Presence of uncontrolled tachyarrhythmia documented in the medical history.
• Medical history of one or more of the following cardiac procedures:

• MI and/or percutaneous coronary intervention (PCI) within the past 3 months
• CABG within the past 3 months
• SAVR or TAVR within the past 6 months
• MVR or TMVR within the past 6 months
• Medical history of any implanted pacemaker device.
• Medical history of cardiac ablation procedure (either for atrial or ventricular arrhythmias) within the past 3 months.
• Presence of chronic pulmonary disease documented in the medical history, defined by one or more of the following:

• Current requirement for continuous home oxygen use
• Hospitalization within the past 12 months for treatment of chronic pulmonary disease
• Significant chronic pulmonary disease defined as FEV1 < 50% of predicted
• If COPD is documented in the medical history and the patient is taking oral or inhaled COPD medication at the time of screening, then a spirometry test is to be performed and patient excluded if FEV1 < 50%.
• Presence of pulmonary hypertension with PASP ≥ 70 mmHg OR PVR > 3.5 Wood units at rest, documented in the medical history or diagnosed during the initial right heart catheterization.