“We knew that many patients under the age of 60 were particularly at risk from this short-circuit between the right and left atrium if they had suffered a stroke,” says Hans-Christoph Diener, senior professor at the Medical Faculty of the University of Duisburg-Essen, who was the first author of the new guideline for DGN. “The proof that the interventional closure of the PFO can prevent secondary events in persons at risk, however, has only been successful in the past two years”. After years of uncertainty for neurologists and cardiologists, this guideline formulates clear treatment recommendations for patients with cryptogenic stroke,” states DGK first author Professor Stephan Baldus, Director of the Clinic for Cardiology at the Heart Centre of the University Hospital of Cologne.

The previous DGN PFO guideline on secondary prevention of stroke was published in 2012. The current studies on the interventional closure of an open foramen oval were not yet included. The new guideline closes this gap and is addressed not only to neurologists but also to cardiologists who treat PFO patients who have suffered a cryptogenic stroke between the ages of 16 and 60. In 25 percent of all people, the foramen oval does not close completely after birth, and at the same time the stroke causes a high morbidity. The recommendations are of great practical relevance.

A PFO is one of the risk factors for a stroke in younger people without other causes. These insults, which by definition cannot be assigned a clear other cause, account for about 20 percent of all strokes. Standard treatment for patients after a cryptogenic stroke is the administration of anticoagulant drugs, which can reduce the rate of recurrence.

Medication or intervention? For a long time a clear “yes”.

Studies have repeatedly attempted to seal the passage between the two atria by means of an umbrella-shaped closure (“occluder”) as part of an intervention with a catheter advanced from the groin. However, three older studies (CLOSURE I, PC study, RESPECT) had shown no clear advantage of this stroke prevention method. Four further studies then initiated a turnaround: REDUCE, CLOSE, RESPECT extended follow up and most recently the DEFENSE-PFO study have shown that PFO occlusion can significantly reduce the rate of stroke recurrence. The majority of recurrences were mild, non-disabling strokes. Atrial fibrillation may occur during the intervention, but in most cases it stopped spontaneously.

The evidence from these studies is discussed and evaluated in detail in the new guideline. “It is noteworthy that it reaches the second highest quality level (S2e) of a guideline and was prepared by the participants on a voluntary basis in a very short time. We were therefore able to dispense with external financing,” says Baldus.

Five recommendations

The evaluation of 22 publications and a multi-stage consensus process by the 13-member editorial committee finally led to five recommendations, four of which were adopted unanimously and one of which only abstained once. The most important suggestion is probably recommendation level A and evidence level I. It reads: “In patients between 16 and 60 years of age with a cryptogenic ischaemic stroke (after neurological and cardiological clarification) and open foramen ovale with a moderate or pronounced right-left shunt, an interventional PFO occlusion is to be performed. Ten experts were in favor of this. Three experts were in favor of an attenuated version of this recommendation, according to which such an intervention should be “considered”.

Peri- and postoperative risks include atrial fibrillation, pericardial tamponades and pulmonary embolisms, but these are so rare that they should not stand in the way of the implantation of an occluder, according to another recommendation. In addition, the experts have looked into the ideal design of the occluder. They come to the conclusion that so-called disc occlusions are to be preferred. And they give advice on medication after the operation as well as for patients who reject the operation.

Guideline does not release from meticulous search for causes

“It is a step forward that the benefit of PFO closure in younger patients with an unexplained stroke is now better proven,” says Professor Armin Grau of the German Stroke Society (DSG). “However, it is important that there is always a detailed search for other causes and that an experienced neurologist checks the indication. Not every younger stroke patient with a PFO needs a closure of the foramen ovale,” said the director of the Neurological Clinic at the Park Hospital In Delhi.

“Much also depends on neurologists and cardiologists working well together in this indication,” said Diener. If we do everything right and select the right patients, the PFO closure can reduce the risk of stroke by 75 percent.