Amrou Sarraj, MD: Approaching PFO-Associated Stroke from a Neurologist’s Standpoint

Amrou Sarraj, MD: Good afternoon. This is Dr Amrou Sarraj. I'm an associate professor of neurology at McGovern Medical School at UTHealth in Houston. We're discussing an important subject to patients’ care, neurologists, cardiologists, and general practitioners, which is reducing stroke recurrence among patients with patent foramen ovale.

We will discuss the etiology and special characteristics of the patients with PFO. We will discuss how to approach these patients from a neurologist's standpoint.

We will also discuss the evidence around the treatment of strokes due to PFO, the different treatment methods, the evidence supporting the closure of the PFO, and in general, the expectations and how to approach these patients from the physician's standpoint, from the patients', and what are the guidelines for practice in these patients.

Patients with PFO-mediated stroke represent a special subpopulation of all patients with strokes. The typical characteristics of patients who would have strokes, they would have underlying vascular risk factors. They are usually elderly patients over the age of 60 in men and 50 in women.

They would have the typical vascular risk factors – high blood pressure, the hypercholesterolemia, the diabetes, or smoking. They usually have the expected imaging characteristics, as in changes in the blood vessels that we would see on the neuroimaging and changes in the brain tissue.

Patients with PFO-mediated strokes are not necessarily the opposite, but are different. They are younger patients. They do not have usually the typical vascular risk factors. So, they are usually less than 60 – mostly, younger than that. They do not have high blood pressure, hypercholesterolemia, and diabetes.

And, when doing the stroke workup, they usually would not have the same findings on vessel imaging as on atherosclerotic changes, prior silent strokes, and white matter changes – usually younger with healthier brains and vessels at baseline, so to speak.

PFO-mediated stroke occurs when there is an opening in the heart with a shunt from the right to the left side of the heart. This PFO opening is a normal finding during the fetal development, and it usually closes after birth. However, in about 75 to 80% of the general population – so, 1 out of 4 to 5 individuals – even without stroke may have a PFO in their heart.

So, this is an important point, that the presence of PFO might be an innocent bystander in some of the stroke patients.

However, if the stroke is PFO-mediated, then this shunt will serve as a passage for a clot that's coming from the lower extremities, the leg or the hip, and traveling through the veins to the right side of the heart, then crossing through the shunt to the left side of the heart, which supplies the brain with blood, ahis clot can travel to the brain and cause the PFO-mediated stroke. So, it is as we call a paradoxical clot because it crosses from the right to the left side.

Stroke is the second most common cause of death overall in the world, and the fifth in the United States. Stroke is the number one leading cause of disability in the United States and the world – I would say preventable disability. And that's the importance of this subject, because if diagnosed and treated well, PFO-mediated strokes can be prevented, so long-term disability can be prevented. Annually, there is about 800,000 strokes occurring in the United States. About one quarter of them are recurrent strokes.

Of all strokes, 80 to 85%, depending on the source, are ischemic. Of those, about 20 to 25% are strokes of unknown cause. The usual term to call those used to be cryptogenic. Recently a new terminology, which is embolic stroke of undetermined source or ESUS, E-S-U-S, is the terminology for that.

So, they account for, as I said, almost one quarter of all ischemic strokes. They are diagnosable and treatable. There is good evidence behind the treatment, which makes it an important subject to prevent recurrence of strokes.

Since cryptogenic, ischemic strokes, or embolic strokes of undetermined source (ESUS) patients present a different subpopulation of all ischemic stroke with, as mentioned, no underlying vascular risk factors, younger age, then furthermore detailed and comprehensive workup is required in these patients, as in all of stroke patients, to be essential neuroimaging of the brain – the MRI, the CT, and vascular imaging of the head and neck would be computed-tomography angiogram or magnetic resonance angiogram – would be done along with transthoracic echocardiogram (TTE), or echo of the heart would be done to assess the usual cause of stroke, which is the atherosclerotic changes in the large vessels outside the brain or inside the brain and the atherosclerotic changes in the small vessels inside the brain, the function of the heart and the brain tissue, as well as the laboratory testing for the diabetes, the cholesterol, the other risk factors.

However, as these patients usually do not have these vascular risk factors and by the name and the definition, they are cryptogenic – so, after doing this initial workup, if there is no etiology is identified – then, before calling them cryptogenic or embolic strokes of undetermined source, further workup should be done, and this further workup would include transesophageal echocardiogram to further assess for PFO, to look at the aortic arch morphology, if there is any diseases, if there's any atherosclerotic changes to look at the left atrial appendage, and if there is a thrombus in the heart that could be the etiology.

Transcranial doppler with bubble study, which also can assess for the presence of PFO, is usually done, and it showed similar sensitivity or even in some studies, better sensitivity to diagnose PFO than TTE.

Apart from that, additional laboratory workup should be done to assess for underlying hypercoagulable state, as in antiphospholipid antibody syndrome, inherited thrombophilias, homocysteinemia, hypercoagulable states also, and with venous thrombosis, and protein C or S deficiency, Factor V Leiden, and more detailed hypercoagulable laboratory testing should be done.

Then, since underlying, undiagnosed atrial fibrillation could be another etiology, then prolonged telemetry monitoring with 30 days event monitor or even implantable monitoring device for heart rhythm should be done. Apart from that and in specific cases, if there is suspicion for underlying cancer, which is a hypercoagulable state by itself, further imaging and laboratory testing should be done.

We mentioned that the underlying source would be the clotting – deep venous thrombosis or thrombosis in the hip and pelvis area – then, further studies to look at the ultrasound of the bilateral lower extremities. MR venogram of the pelvis are important to diagnose if there is underlying clot.

It's important though to note that not every patient, actually most of the patients, when we do the ultrasound of the bilateral lower extremities and the MR venogram of the pelvis, we do not find a clot there, and simply that's because probably the clot is already in the brain and caused the stroke. So, it's not like there is no source. It could not be due to the PFO, so that's important.

And after all of this comprehensive workup, if the etiology is still undetermined, and the patients, based on the TTE, or the TEE, or the transcranial doppler with bubble study deemed to have a PFO, then this patient would be under the potential cryptogenic stroke mediated by PFO.

Thank you for listening to this podcast – an important subject for the general practitioner, the cardiologist, and the neurologist.