Right-to-left shunt for
Pulmonary Arterial Hypertension

 Pulmonary arterial hypertension (PAH) is a rare, but life-threatening disease characterized by elevated blood pressure in the pulmonary arteries. Between 10 and 15 people per million are diagnosed with PAH every year in the United States. There is no cure for PAH and the condition will continue to worsen over time, even with proper treatment. Survival is strongly correlated with the New York Heart Association’s (NYHA) functional class.

In PAH patients presenting with NYHA class I/II symptoms, the median survival after diagnosis is approximately 6 years compared to 2.5 years for NYHA class III patients, and to 6 months for patients with NYHA class IV symptoms.

Clinically, PAH is defined by a resting mean pulmonary artery pressure (mPAP) of ≥25 mmHg with a pulmonary capillary wedge pressure (PCWP) of ≤15 mmHg. In addition, PAH is characterized by pulmonary vascular resistance greater than 3 Wood units in the absence of other causes of precapillary pulmonary hypertension (PH), such as PH due to lung diseases, chronic thromboembolic pulmonary hypertension (CTEPH), or other diseases.

Treatment

The American College of Cardiology (ACC) and the European Society of Cardiology & European Respiratory Society (ESC/ERS) regularly issue guidelines for the diagnosis and treatment of PAH. However, no disease modifying therapies are available and all current therapies aim at reducing symptoms, improving the quality of life (QoL), and slowing disease progression. In many cases combination therapy becomes ineffective over time.

Available pharmacological treatment options include phosphodiesterase-5 inhibitors (PDE5 Inhibitors), endothelin receptor antagonists (ERAs), and prostacyclins. Furthermore, to manage the symptoms of PAH, several drugs (e.g. anticoagulants, calcium channel blockers, diuretics, digoxin) are used off-label. Finally, non-drug therapies such as inhaled oxygen and lifestyle modifications (diet and exercise) are also used to manage symptoms in PAH patients. Surgical intervention (balloon atrial septostomy (BAS), heart-lung transplant) is the only option for patients with advanced PAH.

Interatrial Shunting 

Atrial septostomy (or balloon atrial septostomy, BAS) to create a right-to-left interatrial communication (interatrial shunt), was first described by Rashkind and Miller in 1966. The procedure is regarded as safe and effective, and it remains an important interventional procedure in the palliation of certain rare congenital heart diseases, including in patients with advanced PAH. 

Interatrial shunting has been used successfully to create a right-to-left shunt in patients with PAH. The technique has been shown to reduce right atrial pressure,  to increase left ventricular preload and to increase cardiac output. Specifically, the procedure improves cardiac index and systemic oxygen transport and off-loaded right ventricles show improved function on echocardiography, reduced sympathetic overactivity, and reduced pro-brain natriuretic peptide (proBNP) levels. Meta-analyses have also shown beneficial hemodynamic effects as well as improved short-term survival in PAH patients who underwent atrial septostomy. 

However, the drawbacks of using BAS alone have prevented broader adaptation of the procedure. These include: the unpredictable nature in maintaining a constant interatrial shunt diameter spontaneous shunt closure requiring repeat procedures in 25% or more of patients, and the risk of potentially life-threatening hypoxia that may result from lager atrial septostomies aimed at delaying or preventing spontaneous closure. 

The Atrial Flow Regulator (AFR) 

The AFR is an EU Class III implantable, interatrial, shunting device dedicated to addressing shortcomings of atrial septostomy and improving overall safety and outcomes of interatrial shunting patients with PAH.

The device has a two-disc configuration with a central fenestration to maintain an interatrial shunt, and to allow blood to flow through the central fenestration of the AFR, from the right to the left side of the heart following BAS. For PAH patients, the AFR is available with three different waist-heights and four different disc sizes, to accommodate different thicknesses of the atrial septal wall and overall cardiac anatomy, respectively. In addition, the device is available with  four different fenestration diameters. The diameter of the fenestration is determined by the desired size of interatrial communication using a sizing algorithm. 

The AFR is implanted using standard transcatheter techniques via the femoral vein and under imaging. In brief, following transseptal puncture of the interatrial septum, the puncture site is expanded to the desired shunt diameter using a high-pressure balloon. Thereafter, a transcatheter delivery sheath is used to deliver and implant the AFR using its dedicated pusher cable. 

Following the implant of an AFR, an interatrial right-to-left shunt is created whereby blood from the high-pressure RA flows into the low-pressure LA. This will cause mixing of oxygenated and deoxygenated blood. If not managed properly, this can result in potentially dangerous oxygen desaturation. To adequately and safely manage blood oxygen saturation levels in patients receiving an AFR implant, an algorithm to select adequate AFR fenestration diameters and sizes has been developed.

Human Clinical Experience

The AFR has been successfully implanted in both adult and pediatric PAH patients at centers around the world and as part of the ongoing  PROPHET study. 

Several case reports and studies of PAH patients who received the AFR have been published. The results from these studies show that implanting an AFR results in clinical improvements in patients with severe PAH. These results also support overall device and procedural safety (lack of procedural complications and device-related adverse effects, and , preserved patency of the central fenestration on follow-up).

Access to the AFR 

The AFR is not approved for use in pulmonary arterial hypertension patients. Clinical studies to assess the safety and efficacy of the AFR are ongoing.

AFR echo 1

ECHO showing placement of the AFR in the interatrial septum of a patient.*

AFR echo 2

3D TEE representation showing an implanted AFR*

* Data on file