Iatrogenic Atrial Septal Defect Closure After Transcatheter Mitral Valve Repair: Insights from the MITHRAS Trial

Transcatheter Mitral Valve Repair (TMVr) has emerged as a critical intervention for patients with severe mitral regurgitation who are poor candidates for open-heart surgery. However, the procedure requires transseptal access, which often leaves behind an iatrogenic atrial septal defect (ASD)—a small hole in the wall separating the heart’s upper chambers created during the medical intervention.

Even as these holes are often small, some patients develop significant left-to-right shunting, where oxygenated blood flows back into the right atrium. This raises a critical clinical question: should these defects be closed routinely to improve patient outcomes, or is conservative management sufficient? The MITHRAS trial provides essential evidence to guide this decision.

Understanding the MITHRAS Trial

The MITHRAS trial was designed to evaluate whether the routine percutaneous closure of persistent iatrogenic ASDs provides clinical benefits for patients who have undergone TMVr. The study specifically focused on patients who exhibited “relevant” left-to-right shunting, defined by a Qp:Qs ratio of 1.3 or higher.

Study Design and Patient Demographics

The trial employed an open-label, 1:1 randomized design involving 80 enrollees. The participants were split into two groups:

• Closure Group (n=40): Patients received percutaneous ASD closure using the Figulla Flex II device (Occlutech, Jena, Germany).
• Control Group (n=40): Patients received conservative management.

The average age of the participants was 77 years, and 39% of the cohort were female. To be included, patients had to have a persistent iatrogenic ASD with a Qp:Qs ≥1.3 measured one month after their TMVr procedure. Those with pre-existing interatrial shunts or other planned surgical interventions were excluded.

Key Findings: Does Closure Improve Outcomes?

The primary objective of the MITHRAS trial was to determine if closing the defect improved the patient’s quality of life and survival rates. Despite the technical success of the closures, the clinical results were surprising.

Clinical Endpoints

After one year of follow-up, the trial found that routine closure of iatrogenic ASDs did not result in:

• Improved 6-minute walk distance (a standard measure of functional exercise capacity).
• A reduction in mortality rates.
• A decrease in heart failure (HF) hospitalizations.

The Qp:Qs Paradox

One of the most notable findings of the trial was the impact on the Qp:Qs ratio. In cardiology, Qp:Qs represents the ratio of pulmonary blood flow (Qp) to systemic blood flow (Qs). A ratio above 1.0 indicates a left-to-right shunt, meaning too much blood is recirculating through the lungs.

In the MITHRAS trial, the closure group saw a normalization of this ratio (from a mean baseline of 1.5). However, this physiological normalization did not translate into tangible clinical improvements for the patients. This suggests that for many TMVr patients, the presence of a moderate shunt may not be the primary driver of their symptoms or hospitalizations.

Key Takeaways for Patients and Clinicians

Frequently Asked Questions

What is an iatrogenic atrial septal defect?

An iatrogenic ASD is a hole in the atrial septum (the wall between the left and right atria) caused by a medical procedure. In the case of TMVr, it occurs because doctors must puncture the septum to reach the mitral valve with a catheter.

Why is the Qp:Qs ratio important?

The Qp:Qs ratio helps doctors determine the severity of a shunt. A ratio of 1.3 or higher generally indicates a significant amount of blood is flowing from the left atrium to the right atrium, which can potentially overload the right side of the heart.

Should all iatrogenic ASDs be closed?

Based on the MITHRAS trial, routine closure is not required for every patient, as it may not improve survival or reduce hospitalizations, even when the shunt is hemodynamically significant.

Looking Ahead

The findings from the MITHRAS trial challenge the assumption that correcting a physiological abnormality (the shunt) always leads to a clinical benefit. While percutaneous closure is a safe and effective way to close an ASD, clinicians must weigh the risks and costs of the procedure against the lack of proven improvement in mortality and heart failure rates. Future research may focus on identifying specific subgroups of patients who might actually benefit from closure, rather than applying it as a routine post-TMVr step.