Inhaled Beta-adrenergic Agonists to Treat Pulmonary Vascular Disease in Heart Failure With Preserved EF (BEAT HFpEF): A Randomized Controlled Trial

• Status: Completed
• Trial end date: 2017-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The enormous and rapidly growing burden of Heart Failure with Preserved Ejection Fraction (HFpEF) has led to a need to understand the pathogenesis and treatment options for this morbid disease. Recent research from the investigator's group and others have shown that pulmonary hypertension (PH) is highly prevalent in HFpEF, and right ventricular (RV) dysfunction is present in both early and advanced stages of HFpEF.

These abnormalities in the RV and pulmonary vasculature are coupled with limitations in pulmonary vasodilation during exercise. There are no therapies directly targeted at the pulmonary vasculature that have been clearly shown to be effective in HFpEF. A recent study by Mayo Clinic Investigators has demonstrated pulmonary vasodilation with dobutamine (a beta 2 agonist) in HFpEF. As an intravenous therapy, this is not feasible for outpatient use.

In the proposed randomized, placebo-controlled double blinded trial, the investigators seek to evaluate whether the commonly used inhaled bronchodilator albuterol (a beta 2 agonist), administered through a high-efficiency nebulizer device that achieves true alveolar drug delivery, improves pulmonary vascular resistance (PVR) at rest and during exercise in patients with HFpEF as compared to placebo. This has the potential to lead to a simple cost effective intervention to improve symptoms in HFpEF, and potentially be tested in other World Health Organization (WHO) Pulmonary Hypertension groups. PVR is an excellent surrogate marker for pulmonary vasodilation and has been used in previous early trials of PH therapy.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Adrenergic Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Albuterol

Criteria

Inclusion Criteria:

• Heart Failure with Preserved Ejection Fraction (HFpEF)

• Normal left ventricular ejection fraction (≥50%)

• Elevated Left Ventricular filling pressures at cardiac catheterization (defined as resting Pulmonary Capillary Wedge Pressure>15 mmHg and/or ≥25 mmHg during exercise).

Exclusion Criteria:

• Prior albuterol therapy (within previous 48 hours)

• Current long acting inhaled beta agonist use

• Significant hypokalemia (<3meq/L)

• Significant valvular disease (>moderate left-sided regurgitation, >mild stenosis)

• High output heart failure

• Severe pulmonary disease

• Unstable coronary disease

• Constrictive pericarditis

• Restrictive cardiomyopathy

• Hypertrophic cardiomyopathy