M. Khalid Mojadidi

The Effect of Patent Foramen Ovale Closure on Visual Aura Without Headache or Typical Aura With Migraine Headache

OBJECTIVES The aim of this study was to assess the prevalence of right-to-left (R to L) shunt in patients with visual aura and evaluate the effect of shunt closure on resolution of aura. BACKGROUND Right-to-left shunting is associated with migraine headache (MH) with aura. Some patients present with visual aura without headaches. It is unclear whether visual aura without headache is a form of migraine or a transient neurologic dysfunction. METHODS Of patients referred to the University of California, Los Angeles for suspected patent foramen ovale (PFO), 225 had visual aura with or without MH. Patients were assessed for a shunt and evaluated for MH and/or visual aura. They were divided into 3 groups: 1) visual aura associated with MH; 2) visual aura unrelated in time to MH; and 3) visual aura without MH. The frequency of R to L shunt was compared with a control group of 200 patients. Eighty patients underwent PFO closure. Residual shunts, MH, and visual aura were reassessed after 3 and 12 months. RESULTS The prevalence of R to L shunt in Groups A, B, and C was 96%, 72%, and 67%, respectively, versus 18% in the control group (p < 0.0001). The frequency of shunting was similar in Group B versus Group C, but much higher in all 3 groups compared with control subjects. Twelve months after PFO closure, symptoms of aura were resolved in 52%, 75%, and 80% of patients in Groups A, B, and C, respectively (p = NS). CONCLUSIONS The similar distribution of R to L shunting in all 3 patient groups and the correlation between PFO closure and improvement of aura suggests a similar pathophysiology between the presence of PFO and the visual aura phenomenon, whether or not headache is present in the symptom complex.

Incidence of patent foramen ovale and migraine headache in adults with congenital heart disease with no known cardiac shunts

The purpose of this study was to understand why patients with adult congenital heart disease (CHD) but no obvious shunt have an increased frequency of migraine headaches (MH). CHD patients with no known cardiac shunts (CHD‐NKS), based on their echocardiographic or angiographic procedures, were tested for a right‐to‐left shunt using agitated saline contrast transcranial Doppler (TCD). Medical records of 2,920 patients from the UCLA Adult CHD Center were screened to participate in a study to evaluate the prevalence of MH in adults with CHD; 182 patients (6.23%) had CHD‐NKS; of these, 60 (30%) underwent a TCD; 23 (38%) tested positive and 37 (62%) tested negative for a right‐to‐left shunt (P = 0.01 compared with controls). The frequency of MH was 43% in CHD‐NKS compared with 11% in controls (P < 0.0001). TCD demonstrated right‐to‐left shunting in approximately 2/3 of patients with pulmonary stenosis, the Marfan syndrome and congenitally corrected transposition of great vessels, 1/4 of patients with bicuspid aortic valve, 1/5 of patients with mitral valve prolapse and all patients with Ebsteins anomaly. Approximately half of these experienced MH. Patients who had MH did not show a higher frequency of right‐to‐left shunt when compared with patients without MH (P = 0.57). In conclusion, CHD patients with conditions usually not associated with a shunt have a higher than expected prevalence of PFO which permits intermittent right‐to‐left shunting undetected by standard non‐contrast TTE and TEE; the increased prevalence of right‐to‐left shunting may partially explain the higher than expected frequency of migraines.

A Comparison of Methods to Detect and Quantitate PFO: TCD, TTE, ICE and TEE

At the present time, the diagnosis of a patent foramen ovale (PFO) is based on either imaging of the interatrial septal anatomy that allows direct visualization of the septal defect transesophageal echo [TEE], transthoracic echo [TTE], intracardiac echo [ICE], or by physiologic quantification of the right-to-left shunt (RLS) through the PFO using transcranial Doppler [TCD]. Contrast TEE is currently the standard technique for identifying a PFO and visualization of the atrial septal anatomy. TEE permits an assessment of PFO size, RLS severity and differentiation between an intracardiac and intrapulmonary RLS. A TTE bubble study is the most commonly used imaging modality for the detection of PFO. Though cost-effective and readily available, TTE has a low sensitivity with poor differentiating ability between cardiac and pulmonary RLS. ICE allows detailed visualization of the inter-atrial septum at a resolution comparable to that of TEE. TCD is a highly sensitive test for indirectly assessing the presence of a RLS; some studies report a sensitivity higher than that of TEE but a lower specificity due to TCD’s inability to differentiate between cardiac and pulmonary shunts. This chapter will compare the different techniques and describe the benefits and drawbacks of the various imaging options.

Sensitivity of brachial versus femoral vein injection of agitated saline to detect right-to-left shunts with Transcranial Doppler

Transcranial Doppler (TCD) can detect a right‐to‐left shunt (RLS) with high sensitivity but has a 5% chance of a false negative study. TCD is usually performed with injection of agitated saline into an arm vein. We compared the sensitivity of TCD performed from the brachial versus femoral veins.

Visual migraine aura with or without headache: association with right to left shunt and assessment following transcutaneous closure

Video abstract Video

Device Closure of Patent Foramen Ovale or Medical Therapy for Cryptogenic Stroke: The CLOSURE I Trial

CLOSURE I was the first randomized clinical trial that investigated the use of medical therapy versus medical therapy combined with transcatheter patent foramen ovale (PFO) closure, for the treatment of stroke or transient ischemic attack (TIA). The study included patients between the ages of 18 and 60 who were diagnosed with a cryptogenic stroke or TIA with evidence of a PFO by transesophageal echo. Patients with other identifiable causes for ischemic stroke or TIA, such as carotid artery stenosis, complex aortic arch atheroma, significant left ventricular dysfunction or aneurysm, or atrial fibrillation were excluded. The justification for performing this trial was that observational studies in patients who had suffered a cryptogenic stroke and underwent PFO closure, appeared to have a much lower recurrence rate of stroke compared to patients remained on medical therapy without PFO closure 909 patients were randomized in a 1:1 ratio to either percutaneous PFO closure with the STARFlex Septal Occluder plus antiplatelet therapy with aspirin and clopidogrel, or medical therapy alone with aspirin, warfarin or a combination of both. The primary endpoint was stroke and/or TIA, all-cause mortality within the first 30 days, and death from a neurological cause occurring between 31 days and 2 years. Secondary endpoints were all-cause mortality, stroke, TIA, significant bleeding, and other transient neurologic events of undetermined etiology. After a 2-year follow up, there were no statistical differences in the primary and secondary outcomes when comparing the Closure group versus the Medical Therapy group in both the intention-to-treat and per-protocol populations. The study was heavily criticized for its use of a suboptimal device that resulted in incomplete PFO closure in a large fraction of patients, as well as an increased risk of atrial fibrillation and thrombogenesis compared to the Medical Therapy group.

Clinical Trials to Assess the Relationship Between Patent Foramen Ovale and Migraine Headaches

There are 12 observational studies that describe people with episodic migraines, some of whom are refractory to multiple prophylactic medications, who have complete cessation or significant reduction of their headaches and neurological symptoms following closure of a patent foramen ovale (PFO). Since it is difficult to prove without blinding and randomization that the reduction of migraines following PFO closure is due to closure of the right-to-left shunt and not a placebo effect, dramatic observational reports led to the creation of controlled clinical trials to assess the efficacy of PFO closure in patients with refractory migraines.

The Association of Patent Foramen Ovale and Migraine Headache

Multiple observational studies have identified a link between patent foramen ovale (PFO) and migraine headache. PFO is found in 40 to 60 % of people who have migraine with aura compared to 20 to 30 % in the general adult population. It is hypothesized that migraine, especially migraine with aura or other transient neurologic deficits, may be triggered by chemicals that are ordinarily metabolized during passage through the lungs. However, the presence of a right-to-left shunt allows these chemicals to bypass metabolic alteration in the lungs and gain entry to the arterial circulation in a higher concentration so that upon reaching the brain, they stimulate receptors in susceptible individuals which produces the cerebral migraine phenomena. This hypothesis was derived after observations that PFO closure for other reasons, such as decompression sickness in divers or to prevent cryptogenic stroke, resulted in relief of migraine headaches. Although migraine is not currently an indication for PFO closure, the possible benefit of percutaneous PFO closure as a treatment for migraine headache will be revealed as results from further prospective randomized trials become available.

IS SPIRONOLACTONE EFFICACY IN CONGESTIVE HEART FAILURE AFFECTED BY RACE

It has been hypothesized that efficacy of spironolactone (spirono) in heart failure (HF) with reduced left ventricular ejection fraction (LVEF) may differ by race with less clinical benefit in African-Americans. There is no clinical data regarding other races. From 2002 to 2012, all consecutive