When a younger adult has a stroke and every standard test comes back clean, closing a patent foramen ovale (PFO) can lower the odds of a second stroke, and three randomized trials (RESPECT, CLOSE, and REDUCE) back that up for carefully chosen patients under 60. The catch is in the phrase "carefully chosen." A PFO is common, most of them are harmless, and the whole clinical challenge you face is telling a guilty opening from an innocent one. This article explains how the trials and the RoPE score help draw that line.
Key points#
- A PFO is a small flap between the heart's upper chambers that never fully sealed after birth. Roughly one in four adults has one.
- Finding a PFO after a stroke does not prove it caused the stroke, so patient selection is everything.
- RESPECT, CLOSE, and REDUCE each showed fewer repeat strokes with device closure than with medicine alone in adults under 60.
- The RoPE score estimates how likely a given PFO is the true culprit; higher scores point to more benefit from closure.
- The benefit is real but modest in absolute terms, and closure carries its own small risks, so the decision is a shared one.
Start with the selection problem, not the device#
It is tempting to treat PFO closure as a plumbing question: there is a hole, so close it. The evidence pushes back on that instinct. Because a PFO turns up in about a quarter of healthy people, its mere presence in someone who had a stroke is weak evidence that it did any harm. Think of it like finding an unlocked window after a break-in. The window might be how the intruder got in, or it might have been open the whole time and had nothing to do with it.
The mechanism that would make a PFO dangerous is called paradoxical embolism. A clot forms on the venous side of the circulation, normally destined for the lungs, but instead slips through the flap into the arterial side and lodges in the brain. When a thorough evaluation (brain imaging, prolonged heart-rhythm monitoring, and vascular studies) finds no other cause, the stroke is labeled cryptogenic, and a PFO becomes a plausible but unproven suspect. Everything that follows is an effort to sharpen that suspicion.
The RoPE score: how likely is this PFO the culprit#
The Risk of Paradoxical Embolism (RoPE) score is the tool you reach for first. It assigns points for features that make a PFO a more believable cause: younger age, a cortical (surface) stroke on imaging, and the absence of standard vascular risk factors such as high blood pressure, diabetes, and smoking. The score runs from 0 to 10.
The logic is that a stroke in a 30-year-old with no risk factors has few competing explanations, so if a PFO is present it is more likely to be the reason. A low score (roughly 0 to 3) suggests the opening is probably an innocent bystander and the real cause lies elsewhere. A high score (9 or 10) corresponds to an attributable fraction near 90 percent, meaning the PFO is very likely the true source. Analyses have tied higher RoPE scores to larger relative benefit from closing the PFO, which is why the score does double duty: it helps attribute the stroke and it helps predict who gains from the procedure.
What the three trials actually showed#
Three randomized trials anchor current practice, and reading them in order tells you a useful story.
RESPECT (2013) enrolled 980 patients aged 18 to 60 with a cryptogenic stroke and a PFO, randomizing them to device closure or medical therapy. Its result is frequently misquoted. In the primary intention-to-treat analysis, closure did not reach statistical significance, with a hazard ratio of 0.49 and a confidence interval that crossed 1 (95% CI 0.22 to 1.11, P=0.08). Prespecified per-protocol and as-treated analyses did favor closure, and extended follow-up published in 2017, out to a median of about six years, showed a significant drop in recurrent ischemic stroke. The fair summary is that the original headline was negative and the case strengthened with time.
CLOSE (2017) was designed to test a cleaner question by enrolling only patients with high-risk anatomy: an associated atrial septal aneurysm or a large right-to-left shunt. The separation was stark. No patient in the closure group had a recurrent stroke during follow-up, while strokes occurred in the antiplatelet-only group.
REDUCE (2017) compared closure plus antiplatelet therapy against antiplatelet therapy alone and found recurrent ischemic stroke in 1.4 percent of the closure group versus 5.4 percent of the medication group.
Read together, the three trials moved the field from genuine uncertainty to a reasonably consistent signal: in the right patient, closing a PFO prevents repeat strokes.
Where the evidence runs out#
The trials describe a narrow slice of patients, and their conclusions do not stretch cleanly past it. Almost all of the randomized data come from adults 18 to 60. The 2022 guideline from the Society for Cardiovascular Angiography and Interventions (SCAI) makes a strong recommendation for closure within that age band, but offers only a conditional, low-certainty suggestion for people 60 and older, because the trial evidence thins out there. It also notes that a RoPE score of 7 or higher may flag patients likely to benefit more. Patients whose stroke had another identifiable cause, who had prior atrial fibrillation, or whose workup was incomplete were simply not the people these studies enrolled.
Closure is also not free of harm. Procedural complications, device-related problems, and a well-documented rise in atrial fibrillation (often transient and clustered around the time of the procedure) are part of the trade. And because the yearly recurrence risk on medication is already low, many patients have to be treated to prevent one additional stroke over several years. That arithmetic is exactly why the guideline frames the decision around shared decision-making rather than a reflex to close.
The practical bottom line#
The strongest case for PFO closure is a fairly specific person: an adult under 60, with a genuinely unexplained stroke, a high RoPE score, and often high-risk anatomy, evaluated jointly by neurology and cardiology. For that patient, RESPECT, CLOSE, and REDUCE support closure as a way to cut the risk of another stroke. Outside that profile the evidence weakens, the balance shifts, and the choice belongs to a careful conversation with you in it. Read these trials well and you hold two ideas at once: closure helps the right patient, and identifying the right patient is the hard part.
Sources and further reading
Questions and answers
Does having a PFO mean I will have a stroke?
No. A PFO is present in about a quarter of adults, and the overwhelming majority never have a stroke because of it. On its own, an incidentally discovered PFO is not a reason for closure.
Is closing a PFO better than blood thinners alone?
For selected patients under 60 with an otherwise unexplained stroke, the trials show fewer repeat strokes with closure plus antiplatelet therapy than with medication alone. Whether that edge is worth the procedure depends on the individual's RoPE score, anatomy, and preferences, which is why the decision is shared with a specialist team.
What is a RoPE score used for?
It estimates the probability that a specific PFO actually caused a stroke, using age, stroke pattern, and vascular risk factors. A higher score points to a PFO that is more likely to blame and, in turn, more likely to benefit from closure.