Aspirin's effect on platelet inhibition in migraineurs.

OBJECTIVE: To assess the effect of aspirin on platelet reactivity in migraineurs. BACKGROUND: Migraineurs, particularly women with aura and high monthly migraine frequency, are at risk for ischemic stroke and myocardial infarction (MI). High on-aspirin platelet reactivity (HAPR), or aspirin resistance, has been reported in females and patients with coronary artery disease, and is associated with adverse outcomes. METHODS: Using a single group, pretest/posttest design, 50 migraineurs without prior history of stroke or MI were prospectively treated for 14 to 21 consecutive days with 325 mg generic enteric-coated aspirin, after undergoing a 14-day aspirin washout. Platelet reactivity was measured after aspirin washout and following aspirin treatment. Subjects were screened for HAPR using the VerifyNow™ Aspirin Assay (Accumetrics, San Diego, CA, USA). HAPR was defined as ≥ 460 Aspirin Reaction Units (ARU; primary endpoint). RESULTS: Fifty subjects, 44 (88%) female, aged (mean ± standard deviation) 43 ± 12 years were enrolled. Twelve (24%; 95% CI 12-36%) subjects, all female, had HAPR and were classified as aspirin resistant. Subjects with HAPR had lower baseline hemoglobin levels than those without HAPR (P = .03). Baseline hemoglobin was significantly correlated with final ARU (r = -0.39, P = .005). CONCLUSIONS: Findings of this exploratory study suggest that migraineurs have a higher prevalence of HAPR than healthy volunteers or patients with coronary artery disease taking aspirin 325 mg. The clinical implications of HAPR in migraine warrant further exploration due to the risk of stroke and MI and the potential need for antiplatelet therapy in this population.

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.

Effects of audio relaxation programs for blood pressure reduction in older adults.

BACKGROUND: Stress management is one element of the lifestyle modification that is recommended for blood pressure control. Reduction in sympathetic arousal may be achieved through a series of audio relaxation training. AIMS: The purpose of this study was to evaluate the short-term and long-term effects of two audio relaxation programs for blood pressure reduction in older adults. METHODS: This clinical randomized study consists of 12-sessions of intervention, with one-month and three-month follow up measures. 41 older adults were randomly assigned to either listening to a 12-minute audio relaxation program or a 12-minute Mozart andante. At each session, blood pressures were recorded. RESULTS: For both groups, the reduction in systolic and diastolic blood pressures after the 12-session intervention training was statistically and clinically significant. The reduction in systolic blood pressure was greater in the audio relaxation group than the Mozart group. The adherence to the program at one-month and three-month was 54% and 66% respectively. The blood pressure at one-month and three-month were not significantly different than the initial measurement. CONCLUSIONS: Significant blood pressure reduction can be achieved through a brief 12-minute audio relaxation program with older adults. Guided relaxation may be more effective in lowering blood pressure than plain music.

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.

Unilateral versus bilateral middle cerebral artery detection of right-to-left shunt by power M-mode transcranial doppler.

BACKGROUND AND PURPOSE: Comparison was performed between unilateral and bilateral power M-mode transcranial Doppler to detect right-to-left circulatory shunt (RLS). METHODS: Recorded Doppler data from 87 patients with confirmed RLS referred for transcatheter closure of patent foramen ovale were reanalyzed for embolic tracks (ET) counted from left and right temporal bone windows during bubble study. Unilateral counts were obtained by multiplying each side by 2; bilateral counts were obtained by summing left and right ET. Both unilateral and bilateral ET were converted to a 6-point logarithmic grade. Sex and age group subanalyses were performed. RESULTS: At rest, significantly more ET were detected with bilateral versus unilateral detection (P= .01), but not following Valsalva (P= .13). Unilateral and bilateral detection were equally able to detect large RLS (grades IV or V) following Valsalva (P= 1.00). For the group aged > or =55 years, the right-hand side yielded greater ET than the left-hand side (mean difference 9%+/- 37; 95% confidence interval -3 to 21%) at rest (P= .01), but not following Valsalva (mean difference 1%+/- 25; 95% confidence interval -7 to 9%, P= .10). CONCLUSIONS: Unilateral detection of ET by power M-mode transcranial Doppler is equivalent to bilateral detection to assess RLS.

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.

Perfusion augmentation in acute stroke using mechanical counter-pulsation-phase IIa: effect of external counterpulsation on middle cerebral artery mean flow velocity in five healthy subjects.

BACKGROUND AND PURPOSE: External counterpulsation (ECP) improves coronary perfusion, increases left ventricular stroke volume similar to intraaortic balloon counterpulsation, and recruits arterial collaterals within ischemic territories. We sought to determine ECPs effect on middle cerebral artery (MCA) blood flow augmentation in normal controls as a first step to support future clinical trials in acute stroke. METHODS: Healthy volunteers were recruited and screened for exclusions. Bilateral 2-MHz pulsed wave transcranial Doppler (TCD) probes were mounted by head frame, and baseline M1 MCA TCD measurements were obtained. ECP was then initiated using standard procedures for 30 minutes, and TCD readings were repeated at 5 and 20 minutes. Physiological correlates associated with ECP-TCD waveform morphology were identified, and measurable criteria for TCD assessment of ECP arterial mean flow velocity (MFV) augmentation were constructed. RESULTS: Five subjects were enrolled in the study. Preprocedural M1 MCA TCD measurements were within normal limits. Onset of ECP counterpulsation produced an immediate change in TCD waveform configuration with the appearance of a second upstroke at the dicrotic notch, labeled peak diastolic augmented velocity (PDAV). Although end-diastolic velocities did not increase, both R-MCA and L-MCA PDAVs were significantly higher than baseline end-diastolic values (P<0.05 Wilcoxon rank-sum test) at 5 and 20 minutes. Augmented MFVs (aMFVs) were also significantly higher than baseline MFV in the R-MCA and L-MCA at both 5 and 20 minutes (P<0.05). CONCLUSIONS: ECP induces marked changes in cerebral arterial waveforms and augmented peak diastolic and mean MCA flow velocities on TCD in 5 healthy subjects.

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.

Outcomes after transcatheter closure of patent foramen ovale in patients with paradoxical embolism.

The purpose of the present study was to assess clinical outcomes and closure status after the transcatheter closure of patent foramen ovale. Two hundred thirty-seven consecutive patients (mean age 53 +/- 15 years; 48% men) who underwent patent foramen ovale closure for the prevention of recurrent stroke were evaluated. Primary end points were death, recurrent stroke, and residual right-to-left shunt (RLS). Closure status was monitored at 1, 6, 12, 24, 36, and 48 months after the index procedure by power M-mode transcranial Doppler and was defined by the number of embolic tracks detected after the release of a sustained, calibrated Valsalva maneuver. During a mean follow-up period of 568 +/- 364 days, the cumulative event rate for recurrent stroke (n = 8) was 3.4%, for an estimated event-free survival of 0.94 (SE 0.03). There was a significant difference in the estimated probability of recurrent stroke for patients grouped by age (< or =55 years 1.4% vs >55 years 6.6%, p = 0.03). There were 7 deaths (3.0%), 1 secondary to and 6 unrelated to recurrent strokes, and 3 surgical explantations (1.3%). Event-free survival, defined as freedom from death, stroke, or explantation, was 0.92 (SE 0.02). The magnitude of RLS was significantly less at late follow-up compared with baseline (grade 4.6 +/- 0.7 vs 1.8 +/- 1.6, p <0.001). Complete closure or minimal residual RLS (grade 0 to II) was achieved in 66% of patients. Device type (CardioSEAL or Amplatzer) did not affect the risk for adverse events or the presence of large residual RLS. In conclusion, transcatheter patent foramen ovale closure is associated with a low recurrent stroke rate in long-term follow-up.

Patent foramen ovale and cerebrovascular diseases.

Patent foramen ovale (PFO) has been linked to ischemic strokes of undetermined cause (cryptogenic strokes). PFO-a remnant of fetal circulation when the foramen ovale does not seal after birth-can permit microemboli to escape the pulmonary filter into the intracranial circulation, causing stroke. Coexistent atrial septal aneurysm, pelvic deep vein thrombosis and inherited clotting factor deficiencies could potentiate stroke risk in patients with PFO. Transcatheter PFO closure, a minimally invasive procedure, is one technique used to prevent recurrent cerebrovascular events. A connection between PFO and migraine headache has been conceptualized from retrospective evidence of reduced migraine frequency and severity after PFO closure; however, prospective randomized trials are needed to verify the efficacy of PFO closure on migraine prevention. In this review we discuss embryologic origins, diagnostic techniques and treatment options for prevention of paradoxical embolism thought to be related to PFO, and the relation of PFO to cryptogenic stroke and migraine.

Migraine headache relief after transcatheter closure of patent foramen ovale.

OBJECTIVES: The purpose of this study was to determine the effects of transcatheter patent foramen ovale (PFO) closure on migraine frequency in patients with paradoxical cerebral embolism. BACKGROUND: The prevalence of migraine headache is higher in cryptogenic stroke patients with PFO than in the general population. Previous studies have suggested that closure of the PFO may reduce migrainous symptoms. METHODS: Between April 2001 and December 2003, 162 consecutive patients with paradoxical cerebral embolism underwent transcatheter PFO closure for prevention of recurrent cryptogenic stroke or transient ischemic attack. A one-year retrospective analysis of migraine symptoms before and after PFO closure was performed. RESULTS: Active migraine was present in 35% (57 of 162) of patients, and 68% (39 of 57) experienced migrainous aura; 50 patients were available for analysis at one year. Complete resolution of migraine symptoms occurred in 56% (28 of 50) of patients, and 14% (7 of 50) of patients reported a significant (>or=50%) reduction in migraine frequency. Patients reported an 80% reduction in the mean number of migraine episodes per month after PFO closure (6.8 +/- 9.6 before closure vs. 1.4 +/- 3.4 after closure, p < 0.001). Results were independent of completeness of PFO closure at one year. CONCLUSIONS: In patients with paradoxical cerebral embolism, migraine headaches are more frequent than in the general population, and transcatheter closure of the PFO results in complete resolution or marked reduction in frequency of migraine headache.

Power m-mode transcranial Doppler for diagnosis of patent foramen ovale and assessing transcatheter closure.

BACKGROUND AND PURPOSE: Transcatheter closure of patent foramen ovale (PFO) can benefit from a less invasive diagnostic method than transesophageal echocardiography (TEE). Thirty-three gate power m-mode transcranial Doppler (pmTCD) was evaluated for its accuracy in diagnosis of PFO and utility in evaluating residual intracardiac right-to-left shunt (RLS) following transcatheter closure. METHODS: The sensitivity of pmTCD and single-gate TCD (sgTCD) to detect contrast bubble emboli through RLS was compared during transcatheter PFO closure. During 100 preclosure diagnostic evaluations and in 81 postclosure assessments, embolic tracks on pmTCD were counted following intravenous contrast injections and were graded using a 6-level logarithmic scale. The accuracy of TEE and pmTCD was separately compared to PFO anatomical findings during transcatheter closures. RESULTS: There were significantly more microemboli detectable on pmTCD (322 +/- 166; 95% confidence interval [CI], 388-257) than on sgTCD (186 +/- 109; 95% CI, 229-143; P < .001). McNemar change tests suggest that the diagnostic capabilities of pmTCD and TEE for detecting PFO are comparable and correspond to the anatomical findings determined during cardiac catheterization (P = .69 and .45, respectively). During 6-month postclosure evaluation (mean = 185 days), 66% of the patients demonstrated successful closure without significant RLS (ie, grades 0, I, or II), and 34% were found to have incomplete closure with significant RLS (ie, grades III, IV, or V). CONCLUSIONS: pmTCD provides greater sensitivity to contrast bubble emboli than does sgTCD. Among candidates for transcatheter closure, pmTCD provides an improved noninvasive method for diagnosing PFO and evaluating transcatheter closure.