BACKGROUND Most approaches to the creation of an interatrial shunt require placement of a permanent implant to maintain patency. OBJECTIVES The goal of this study was to investigate the safety and efficacy of a no-implant interatrial shunt for patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF). METHODS This was a multicenter, uncontrolled study of patients with HFpEF/HFmrEF and NYHA functional class $II, ejection fraction >40%, and pulmonary capillary wedge pressure (PCWP) during supine exercise >= 25 mm Hg with PCWP-to-right atrial gradient >= 5 mm Hg. Follow-up was through 6 months with imaging to assess shunt durability. RESULTS A total of 28 patients were enrolled: mean age was 68 +/- 9 years, and 68% were female. Baseline resting and peak exercise PCWP were 19 +/- 7 mm Hg and 40 +/- 11 mm Hg, respectively. All procedures displayed technical success with confirmation of left-to-right flow (shunt diameter 7.1 +/- 0.9 mm). At 1 month, peak exercise PCWP decreased 5.4 +/- 9.6 mm Hg (P 1/4 0.011) with no change in right atrial pressure. There were no serious device or procedure-related adverse events through 6 months. Mean 6-minute walk distance increased 101 +/- 71 meters (P < 0.001); Kansas City Cardiomyopathy Questionnaire Overall Summary Score increased 26 +/- 19 points (P < 0.001); N-terminal pro-B-type natriuretic peptide decreased 372 +/- 857 pg/mL (P 1/4 0.018); and shunt patency was confirmed with unchanged diameter. CONCLUSIONS In these feasibility studies of a no-implant interatrial shunt, HFpEF/HFmrEF shunts exhibited stability with favorable safety and early efficacy signals. The results show promise toward this new approach for treating patients with HFpEF/HFmrEF and an appropriate hemodynamic profile. (Evaluation of the Safety and Feasibility of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction [ALLEVIATE-HF-1]; NCT04583527; Evaluation of the Safety and Effectiveness of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction [ALLEVIATE-HF-2]; NCT04838353) (J Am Coll Cardiol HF 2023;11:1121-1130) (c) 2023 by the American College of Cardiology Foundation.

Introduction Chronic heart failure (HFpEF and HFrEF) remains an important area of unmet need despite current best medical therapies available. Implantable interatrial shunt devices may improve quality of life and functional capacity with favorable safety signals but require permanent implantation to maintain patency. We report the 6-month clinical outcomes of a no-implant approach to interatrial shunting across three studies: ALLEVIATE-HF-1 and ALLEVIATE-HF-2 for HFpEF, and a dedicated HFrEF study. Methods Patients aged ≥ 40 years, NYHA class II, III or ambulatory IV and elevated left atrial pressure (PCWP) during supine ergometry were included in the studies. Baseline assessments included echocardiography, exercise right heart catheterization, KCCQ and 6MWT. Femoral venous access and standard transseptal catheterization techniques were employed. The device was utilized to excise a segment of the interatrial septum using a pulse of radiofrequency energy to create a shunt under fluoroscopic and echocardiographic guidance. Results A total of 28 HFpEF and 5 HFrEF patients were enrolled. Mean left ventricular ejection fraction was 61 ± 8% and 30 ± 8% in HFpEF and HFrEF patients, respectively. Procedures were successful with no device or procedure-related adverse events. Six-month outcomes are reported in the table. Transthoracic echocardiography and computer tomography confirmed all shunts remained patency (n=30). There were no significant changes in right-sided structure or function. No device or procedure-related serious adverse events occurred upon discharge and through 6 months. Conclusions This early feasibility clinical experience demonstrates procedural safety and feasibility of the Alleviant no-implant interatrial shunt creation with a promising efficacy signal through 6 months in patients with HFpEF and HFrEF. Enrollment for the randomized sham-controlled pivotal study (ALLAY-HF, FDA IDE approved) is currently underway.

Heart failure with preserved ejection fraction (HFpEF) represents a major unmet clinical need with limited treatment options. Implantable interatrial shunt devices have shown favorable safety and efficacy signals; however, they require permanent implantation to maintain shunt patency.

Background: Heart failure with preserved ejection fraction represents a major unmet clinical need with limited treatment options. Recent device therapies under investigation have focused on decompression of the left atrium through an implantable interatrial shunt. Although these devices have shown favorable safety and efficacy signals, an implant is required to maintain shunt patency, which may increase the patient risk profile and complicate subsequent interventions requiring transseptal access. Methods: The Alleviant System is a no-implant approach to creating an interatrial shunt using radiofrequency energy to securely capture, excise, and extract a precise disk of tissue from the interatrial septum. Acute pre -clinical studies in healthy swine (n = 5) demonstrated the feasibility of the Alleviant System to repeatably create a 7 mm interatrial orifice with minimal collateral thermal effect and minimal platelet and fibrin deposition observed histologically. Results: Chronic animal studies (n = 9) were carried out to 30-and 60-day time points and exhibited sustained shunt patency with histology demonstrating completely healed margins, endothelialization, and no trauma to adjacent atrial tissue. Preliminary clinical safety and feasibility were validated in a first-in-human study in pa-tients with heart failure with preserved ejection fraction (n = 15). All patients demonstrated shunt patency by transesophageal echocardiographic imaging at 1, 3, and 6 months, as well as cardiac computed tomography imaging at 6-month follow-up timepoints. Conclusions: Combined, these data support the safety and feasibility of a novel no-implant approach to creating an interatrial shunt using the Alleviant System. Continued follow-up and subsequent clinical studies are currently ongoing.