Cindy J. Fuller

Migraineurs with patent foramen ovale have larger right-to-left shunt despite similar atrial septal characteristics.

The objective of the study was to assess differences in proportion of large right-to-left shunt (RLS) and atrial septal characteristics between migraineurs and non-migraineurs referred for transcatheter closure of patent foramen ovale (PF0). This retrospective study took place in a large metropolitan medical centre. The patients were migraineurs with aura (n=52), migraineurs without aura (n=19) and non-migraineurs (n=149). RLS was evaluated before closure using bilateral power m-mode transcranial Doppler at rest and after calibrated, sustained Valsalva manoeuvre, and graded with a validated 0–5 scale. Intracardiac echocardiography was used to assess atrial septal characteristics. Migraineurs had a higher proportion of large RLS (Grade IV or V) than nonmigraineurs at rest and after calibrated Valsalva (rest, p=0.04; Valsalva, p=0.01). Atrial septal characteristics were similar between groups. Migraine is associated with larger RLS at rest and strain; however migraine status does not predict PFO characteristics.

Frequency of Migraine Headache Relief Following Patent Foramen Ovale "Closure" Despite Residual Right-to-Left Shunt

Retrospective studies have shown improvement in migraines after patent foramen ovale (PFO) closure. To date, no study has evaluated whether the completeness of closure affects headache status; therefore, the objective of this study was to evaluate the impact of residual right-to-left shunt (RLS) on migraine symptoms after transcatheter PFO closure in migraineurs with and without aura. This was a small-series, single-center, retrospective analysis of late follow-up data on 77 patients with presumed paradoxical embolism and migraine who underwent PFO closure for secondary stroke prevention. Power M-mode transcranial Doppler was used to assess RLS at baseline and 6 and 12 months after closure. A standardized migraine questionnaire was administered at baseline and 6, 12, and 24 months after closure. Fifty-five (71%) patients had migraine with aura. Final closure and migraine status were available for 67 patients; 23 (34%) had incomplete PFO closure, defined as 30 embolic tracks detected at final power M-mode transcranial Doppler examination (median 366 days, 95% confidence interval 332 to 474). Migraine relief (> or = 50% reduction in frequency) was independent of closure status (77% complete closure vs 83% incomplete closure, p = 0.76) at late follow-up (540 days, 95% confidence interval 537 to 711). Migraineurs with aura were 4.5 times more likely to experience migraine relief than migraineurs without aura. In conclusion, migraine relief may occur despite residual RLS after transcatheter PFO closure, which may suggest a reduction in RLS burden below a neuronal threshold that triggers migraine; however, this warrants further investigation. Migraine with aura may be an independent predictor of relief after PFO closure.

The effect of vitamin E and vitamin C supplementation on LDL oxidizability and neutrophil respiratory burst in young smokers.

Objective: The purpose of this study was to determine the effect of vitamin E and/or vitamin C supplementation on low-density lipoprotein (LDL) oxidizability and neutrophil (PMN) superoxide anion production in young smokers. Methods: Thirty smokers with a <5 pack-year history were randomly assigned to take placebo; vitamin C (1 g/day); vitamin E (400 IU/day); or both vitamins in a double-blind fashion. Subjects took the supplements for 8 weeks. At weeks 0 and 8, blood was collected for isolation of LDL and PMN, and for antioxidant vitamin analysis. LDL was oxidized with a copper (Cu) catalyst, and oxidation was measured by formation of conjugated dienes over a 5-hour time course. Lag times and maximum oxidation rates were calculated from the time course data. PMN superoxide anion release was assessed by respiratory burst after stimulation with phorbol ester and opsonized zymosan, and their ability to oxidize autologous LDL following treatment with the above stimuli was measured with the conjugated diene assay. Results: Subjects who received vitamin E alone had a significant increase in the lag phase of Cu-catalyzed LDL oxidation (week 0, 118 ± 31 min vs. week 8, 193 ± 80 min, mean ± SD, p < 0.05), whereas the vitamin C and placebo groups had no changes in LDL oxidation kinetics. The group receiving both vitamins E and C had a significant reduction in oxidation rate (week 0, 7.4 ± 2.3 vs. week 8, 5.1 ± 2.1, p < 0.05). There were no significant changes for any group in PMN superoxide anion production or PMN LDL oxidation after stimulation with either phorbol ester or opsonized zymosan. Plasma and LDL vitamin E concentrations were significantly increased in both groups that received vitamin E. The subjects who received vitamin C alone had no significant change in plasma vitamin C concentrations; however, when data were pooled from both groups who received vitamin C, the increases were significant. Conclusion: Vitamin E supplementation of young smokers was effective in reducing Cu-catalyzed LDL oxidizability; however, vitamin E and/or C supplementation showed few significant effects on the more physiologically relevant PMN function. This casts doubt on the ability of antioxidant supplementation to reduce oxidative stress in smokers in vivo. Therefore, smoking cessation remains the only means by which young smokers can prevent premature coronary heart disease.

Diagnosis of Secondary Source of Right-to-Left Shunt With Balloon Occlusion of Patent Foramen Ovale and Power M-Mode Transcranial Doppler

OBJECTIVES We sought to assess the prevalence of secondary right-to-left circulatory shunt (RLS) in patients undergoing transcatheter closure of patent foramen ovale (PFO) as detected by power M-mode transcranial Doppler (TCD) and intracardiac echocardiography. BACKGROUND Prevalence of residual RLS in late follow-up after PFO closure may be as high as 34%. Other cardiac and noncardiac sources of RLS may coexist and obscure PFO closure evaluation. METHODS Eighty-eight patients who underwent transcatheter PFO closure to prevent recurrent paradoxical cerebral embolism between June 2005 and December 2006 were evaluated for a secondary source of RLS. Before device deployment, a sizing balloon was inflated in the PFO tunnel and agitated saline contrast was injected into the inferior vena cava. Clinically significant secondary RLS was defined as >10 embolic tracks on TCD at rest or immediately after calibrated (40 mm Hg), sustained (10 s) respiratory strain, with corresponding negative color-flow Doppler. Late residual RLS was evaluated in all patients with TCD and transthoracic echocardiography (mean: 192 days; 95% confidence interval [CI]: 161 to 223 days). RESULTS The sample (n = 84) was 59% female, age 49 +/- 14 years. Seventeen patients (20%; 95% CI: 11.7 to 28.8) had secondary RLS during balloon occlusion. At late follow-up (n = 66), 13 of 14 (93%) patients with secondary RLS and 23 of 52 (44%) patients without secondary RLS had residual RLS (p = 0.002). CONCLUSIONS This is the first report to systematically assess the prevalence of secondary RLS in patients undergoing PFO closure. Residual RLS detected by TCD may be due to secondary RLS, which may have implications for clinical outcomes.

Stroke Prevention in Atrial Fibrillation: Atrial Appendage Closure

The left atrial appendage (LAA) is the primary nonvalvular cause of cardioembolic stroke in patients with atrial fibrillation (AF). Warfarin and direct thrombin inhibitors such as dabigatran are presumed to prevent formation of LAA thrombus, and are first-line treatments to prevent ischemic stroke in AF. However, these medications carry many contraindications such as hemorrhage, and can interact with many drugs and supplements. Epicardial and endovascular techniques for occlusion of LAA are being explored, whether to mitigate the need for anticoagulation in patients at risk of bleeding or as a first-line therapy to reduce the risk of thromboembolic stroke. The purposes of this article are to 1) review the LAA structure and its potential contribution to ischemic stroke; 2) discuss the results of surgical and endovascular trials of LAA occlusion on risk of stroke and adverse events in AF patients; and 3) present early data on devices in development.

Effects of increasing doses of alpha-tocopherol in providing protection of low-density lipoprotein from oxidation

In this study, we tested whether 1,200 IU/day of alpha-tocopherol was more potent than 400 and 800 IU of alpha-tocopherol in decreasing low-density lipoprotein (LDL) oxidative susceptibility in a 2-month study. The decrease in LDL oxidation was significantly greater with 1,200 IU/day than 400 IU/day.

Relative bioavailability of β-carotene from supplement sources

Abstract The purpose of this study was to compare the acute plasma response to β-carotene (βC) from supplements in healthy subjects. Ten healthy subjects ingested 30 mg/day of βC for 3 days from 3 different supplements in a randomized crossover design: synthetic βC in water-miscible (10%) beadlets; synthetic βC gelcaps; and mixed carotenoids from Dunaliella salina gelcaps. Plasma carotenoid determinations were performed at baseline and after each 3-day supplementation phase. Amounts of βC in the supplements were 23.2 ± 0 mg for beadlets; 28.4 ± 0.9 mg for βC gelcaps; and 29.8 ± 0.6 mg for D. salina gelcaps. Plasma βC response for beadlets was significantly greater than for either gelcap preparation ( p in vitro and/or in vivo investigations.

Aspirin's Effect on Platelet Inhibition in Migraineurs

Objective.— To assess the effect of aspirin on platelet reactivity in migraineurs.

Unilateral versus Bilateral Middle Cerebral Artery Detection of Right‐to‐Left Shunt by Power M‐Mode Transcranial Doppler

Comparison was performed between unilateral and bilateral power M‐mode transcranial Doppler to detect right‐to‐left circulatory shunt (RLS).

Migraine and Patent Foramen Ovale: State of the Science

Migraine is a prominent cause of recurrent pain, affecting 12% of the population. In several case series, approximately 50% of migraineurs with aura were found to have patent foramen ovale (PFO). The pathophysiological mechanism is speculated to be passage of microemboli and vasoactive chemicals through the PFO, thereby evading pulmonary filtration and triggering migraine symptoms. This article presents the results of retrospective and prospective research studies documenting the effects of PFO closure on migraine symptoms and presents emerging theories on possible pathologic mechanisms that may partially explain the increased risk of ischemic stroke in the migraine population. Finally, evidence-based recommendations are presented for health care providers for managing patients who have migraine and PFO.