Older Age Tied to Higher Risk of Recurrent Cerebral Ischemia in PFO Closure Patients
Recurrent stroke and/or TIA after PFO closure is more common among older patients and is unrelated to residual shunt and paradoxical embolism, according to a study published online June 23, 2015, ahead of print in Catheterization and Cardiovascular Interventions.
“The appropriate selection of candidates [for] closure and the monitoring of the progression of underlying vascular or arrhythmic disease are, therefore, crucial,” write Paolo Scacciatella, MD, of Azienda Ospedaliera Universitaria Città della Salute e della Scienza (Turin, Italy), and colleagues.
The investigators looked at 458 consecutive high-risk patients who underwent PFO closure for cryptogenic stroke at 2 centers between 2000 and 2013. The 2 most commonly used devices were the Amplatzer PFO Occluder and the Amplatzer Cribriform (both St. Jude Medical).
Patients were divided into 2 groups by age: 55 years and older (n = 151) and younger than 55 years (n = 307). Those in the older cohort presented more frequently with hypertension, diabetes, dyslipidemia, and CAD (P = .001 for all) than did those in the younger cohort. There were no differences between the study arms in terms of PFO indication or anatomical features.
Age Predicts Recurrent Ischemia Risk
Procedural success was achieved in all patients, but 3 patients in the older group simultaneously received PCI compared with none in the younger group (P = .03). Periprocedural complications were recorded for 6 older patients (2 cases of A-fib, 2 of pseudoaneurysms, and 1 each of arteriovenous fistula and deep vein thrombosis) and 8 younger patients (3 cases of A-fib, 2 each of supraventricular paroxysmal tachycardias and ST elevations, and 1 of TIA).
During a mean follow-up of 4.46 years, recurrent cerebral ischemia (primary endpoint) was more frequent in the older age group, though none of the patients with events had significant residual shunt. There were slightly higher rates of stroke and TIA among older patients, but other outcomes did not differ between groups (table 1).
Kaplan-Meier estimated event-free survival was higher for younger patients at the end of follow-up (P = .008).
On multivariate analysis, age ≥ 55 years proved to be the only independent predictor of recurrent cerebral ischemia (HR 8.4; 95% CI 1.5-83.2).
Recurrence-Free Survival ‘Long’
“Existing data support the safety of transcatheter PFO closure but are conflicting regarding its superiority [over] medical therapy, despite a tendency in favor of the interventional treatment that reached a significant difference only in patients with a severe shunt [or septal aneurysm] and when both strokes and TIAs were considered,” the authors write, adding that most RCTs have focused on only a younger patient cohort.
“Older patients have ‘per se’ more risk factors for stroke independent from PFO… and therefore a higher rate of recurrence is expected,” Dr. Scacciatella and colleagues say. “In addition, older subjects are more likely affected by carotid atherosclerosis and structural heart diseases increasing left atrial filling pressures, which can promote the development of [A-fib].”
The study is consistent with prior research “but adds the demonstration of a long mean recurrence-free survival time after the procedure,” they observe, noting that the lack of residual shunt in patients who developed recurrent ischemia “is another key element.”
As such, “we can affirm that in a specific population of older people the vast majority of events occurring after the closure are unrelated to paradoxical embolism but most likely are related to age itself, which is the only independent predictor of recurrence,” the authors comment.
Data Reaffirm Importance of Age
In an email with TCTMD, Sammy Elmariah, MD, MPH, of Massachusetts General Hospital (Boston, MA), said the results are not surprising and “lend further support to our belief that PFO closure is safe and that it is associated with incredibly low recurrent cerebrovascular events in well-selected patients.”
In the prior Risk of Paradoxical Embolism (RoPE) study, the 10-point RoPE score uses age to account for half of the possible points, he commented. Though the score is not yet validated, Dr. Elmariah said, it will be useful in evaluating future PFO closure patients by integrating age with other factors such as hypertension, diabetes, and tobacco use.
David E. Thaler, MD, PhD, of Tufts Medical Center (Boston, MA), who served as coprincipal investigator of the RoPE study, told TCTMD in a telephone interview that PFOs are seen in only half of the patient population with cryptogenic stroke. But even when present, the defect may not be the actual cause of stroke.
In the current study, he said, the authors “[assumed] that all of these patients had PFO-related strokes—not that they had strokes and happened to have a PFO.” From past experience, Dr. Thaler continued, “we know that a lot of first strokes, especially in the older people, probably had nothing to do with their PFOs.”
Hence, this paper does not contribute much to the literature “apart from just a new population, which is relatively small compared to the population we were studying,” he said.
Properly Defining Cryptogenic Stroke
A big issue with PFO studies in general, Dr. Thaler observed, is the inconsistency with which cryptogenic stroke is defined. “You have to look at the blood vessels, the heart, and the rhythm of the heart, and there is not very good agreement on [when] an individual patient has been ‘completely evaluated,’” he said.
“Some would argue, including me, that TEE is an important part of a complete evaluation,” Dr. Thaler said, adding that the current study did not specify exactly how they identified cryptogenic stroke patients, as not all even received TEE.
Dr. Elmariah emphasized the importance of ruling out A-fib and atherosclerotic disease first and foremost as well as longer-term monitoring. “Second, more attention must be given to the presence of risk factors for cerebrovascular disease,” he said. “Third, as the authors have emphasized, characteristics and location of the ischemic lesion on brain imaging must be weighed in the decision.”
Lastly, he said, given the vagueness of a TIA diagnosis, “it seems prudent to therefore model one’s clinical practice on the RESPECT and PC trials by either excluding TIA or only treating those with neuroradiographic confirmation of a cerebral ischemic lesion.”
Ultimately, the field needs data from a “well-powered randomized clinical trial with stringent criteria to enroll only patients with high likelihood of cryptogenic stroke that demonstrates superiority of PFO closure over medical therapy in reducing recurrent neurologic events,” Dr. Elmariah concluded. “With the recent completion of enrollment within the REDUCE trial, we’ll hopefully have more data to consider in early 2017.”
Scacciatella P, Meynet I, Presbitero P, et al. Recurrent cerebral ischemia after patent foramen ovale percutaneous closure in older patients: a two-center registry study. Catheter Cardiovasc Interv. 2015;Epub ahead of print.
- Drs. Scacciatella and Elmariah report no relevant conflicts of interest.
- Dr. Thaler reports receiving research funding from the NIH and compensation from St. Jude for serving on the steering committee of the RESPECT trial.