Rationale and Design of the Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (Reduce LAP-HF) Trial

Objective: Heart failure with preserved ejection fraction (HFpEF) is characterized by elevated left atrial pressure during rest and/or exercise. The Reduce LAP-HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial will evaluate the safety and performance of the Interatrial Shunt Device (IASD) System II, designed to directly reduce elevated left atrial pressure, in patients with HFpEF. Methods: The Reduce LAP-HF Trial is a prospective, nonrandomized, open-label trial to evaluate a novel device that creates a small permanent shunt at the level of the atria. A minimum of 60 patients with ejection fraction >= 40% and New York Heart Association functional class 171 or IV heart failure with a pulmonary capillary wedge pressure (PCWP) >= 15 mm Hg at rest or >= 25 mm Hg during supine bike exercise will be implanted with an IASD System II, and followed for 6 months to assess the primary and secondary end points. Safety and standard clinical follow-up Will continue through 3 years after implantation. Primary outcome measures for safety are periprocedural and 6-month major adverse cardiac and cerebrovascular events (MACCE) and systemic embolic events (excluding pulmonary thromboembolism). MACCE include death, stroke, myocardial infarction, or requirement of implant removal. Primary outcome measures for device performance include success of device implantation, reduction of PCWP at rest and during exercise, and demonstration of left-to-right flow through the device. Key secondary end points include exercise tolerance, quality of life, and the incidence of heart failure hospitalization. Conclusion: Reduce LAP-HF is the first trial intended to lower left atrial pressure in HFpEF by means of creating a permanent shunt through the atrial septum with the use of a device. Although the trial is primarily designed to study safety and device performance, we also test the pathophysiologic hypothesis that reduction of left atrial pressure will improve symptoms and quality of life in patients with HFpEF.