Inhaled Beta-adrenergic Agonists to Treat Pulmonary Vascular Disease in Heart Failure With Preserved EF (BEAT HFpEF): A Randomized Controlled Trial
Condition: Congestive Heart Failure; Heart Failure, Left-Sided; Left-Sided Heart Failure
MeSH terms: Heart Failure; Vascular Diseases
Intervention: Albuterol; Saline placebo
Intervention description: : Experimental: Inhaled albuterol
2.5 mg inhaled albuterol through a high efficiency nebulizer as a single dose; Saline inhaled through a nebulizer as a single dose
Intervention MeSH terms: Albuterol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Heart Failure with Preserved Ejection Fraction; Pulmonary Hypertension

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.
    

Eligibility 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