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Non-vitamin K antagonist oral anticoagulants (NOACs) reduce the risk of thromboembolism in patients with atrial fibrillation (AF). There has been no head-to-head comparison of the effect of these agents on ex vivo thrombotic and thrombolytic status. Enhanced platelet reactivity and impaired endogenous thrombolysis are risk factors for recurrent thrombotic events. We aimed to assess the comparative effect of NOACs and warfarin using an ex vivo test of thrombosis and thrombolysis. Eighty patients with newly diagnosed non-valvular AF were tested before, and after being established on apixaban (n = 20), dabigatran (n = 20), rivaroxaban (n = 20), or warfarin (n = 20). Thrombotic status was assessed with the automated, point-of-care Global Thrombosis Test (GTT) that assesses both platelet reactivity and endogenous thrombolysis from native blood. The time taken to form an occlusive thrombus (occlusion time, OT) and the time required to restore flow through endogenous thrombolysis (lysis time, LT) were measured. All anticoagulants caused OT prolongation compared to baseline (apixaban 403 ± 102s vs. 496 ± 125s, p = 0.006; dabigatran 471 ± 106s vs. 656 ± 165s, p < 0.00001; rivaroxaban 381 ± 119s vs. 579 ± 158, p < 0.00001; warfarin 420 ± 145s vs. 604 ± 124s, p < 0.00001). Apixaban reduced LT from baseline (1895[1702-2167]s vs. 1435[347-1990]s; p = 0.006). A trend for LT reduction was seen with other NOACs (dabigatran 1594[1226-2069]s vs. 1539[561-2316]s, p = 0.499; rivaroxaban 2085[1366-2428]s vs. 1885[724-2420]s, p = 0.295) but not with warfarin (1490[1206-1960]s vs. 1776[1545-2334], p = 0.601). Our results suggest that NOACs and warfarin have a similar favorable effect on reducing platelet reactivity. All NOACs exhibited a trend toward enhancing endogenous thrombolytic status, although this was significant only for apixaban. This raises the possibility of using NOACs to enhance impaired endogenous fibrinolysis in patients at high-thrombotic risk.

Objectives We sought to prove that device closure of atrial septal defect (ASD) in older patients not only improves cardiac function but also results in symptomatic relief by improving functional class. Background Atrial septal defect accounts for approximately 10% of all congenital cardiac defects. It is possible that ASD closure in older patients may derive benefits, though this is not well established. We therefore aim to prospectively assess the clinical status and functional class of older patients after transcatheter ASD closure. Methods This was a prospective study of all patients age 40 years or more who underwent device closure of a secundum ASD between April 2004 and August 2006. Investigations including atrial and brain natriuretic peptide levels, electrocardiography, chest X-ray, transthoracic echocardiogram, 6-min walk test, and quality of life questionnaire were performed before and at 6 weeks and 1 year after the procedure. Results Twenty-three patients (median age 70 years, 13 women) had transcatheter device closure of ASD. Median ASD size was 18 mm (range 9 to 30 mm). Median pulmonary artery pressure was 22 mm Hg (range 12 to 27 mm Hg). At 1 year, New York Heart Association functional class improved (p = 0.004) in 16 patients with significant improvement in 6-min walk-test distance (p = 0.004) and physical (p = 0.002) as well as mental health score (p = 0.03). There were no major complications. One year following closure there was a significant change in left ventricular end-diastolic (p = 0.001) and end-systolic dimensions (p = 0.001) and also significant reduction in right ventricular end-diastolic dimension (p Conclusions Our data demonstrated that ASD closure at advanced age results in favorable cardiac remodeling and improvement of functional class.

Background— Patent foramen ovale (PFO) is prevalent in patients with migraine with aura. Observational studies show that PFO closure resulted in migraine cessation or improvement in ≈80% of such patients. We investigated the effects of PFO closure for migraine in a randomized, double-blind, sham-controlled trial. Methods and Results— Patients who suffered from migraine with aura, experienced frequent migraine attacks, had previously failed ≥2 classes of prophylactic treatments, and had moderate or large right-to-left shunts consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure. Patients were followed up for 6 months. The primary efficacy end point was cessation of migraine headache 91 to 180 days after the procedure. In total, 163 of 432 patients (38%) had right-to-left shunts consistent with a moderate or large PFO. One hundred forty-seven patients were randomized. No significant difference was observed in the primary end point of migraine headache cessation between implant and sham groups (3 of 74 versus 3 of 73, respectively; P =0.51). Secondary end points also were not achieved. On exploratory analysis, excluding 2 outliers, the implant group demonstrated a greater reduction in total migraine headache days ( P =0.027). As expected, the implant arm experienced more procedural serious adverse events. All events were transient. Conclusions— This trial confirmed the high prevalence of right-to-left shunts in patients with migraine with aura. Although no significant effect was found for primary or secondary end points, the exploratory analysis supports further investigation. The robust design of this study has served as the model for larger trials that are currently underway in the United States and Europe.

Objectives: (1) To define patent foramen ovale (PFO) morphology using balloon assessment and identify those with long tunnel type morphology. (2) To describe a novel technique of detunnelisation to facilitate PFO device closure in patients with long tunnel PFO morphology. Background: An appreciation that PFO morphology varies from simple defects through to long tunnel-like defects is important for their successful transcatheter closure. Using standard closure techniques for long tunnels can be problematic. Methods: Consecutive patients who underwent transcatheter PFO closure from April 1, 2005 to March 31, 2006 had assessment of PFO morphology using a compliant sizing balloon. The sites of constraint of the balloon allowed identification of the PFO entrance, exit, and length. The PFO was classified as being a long tunnel when the length was greater than the diameter of either the entrance or exit. Those with a long tunnel had detunnelisation performed and the defect was then closed. Results: 44 patients (32 females), mean age 50 years were studied. On balloon assessment 10 (23%) met the criteria for long tunnels. Detunnelisation allowed successful closure with the STARFlex (NMT Medical, Boston, MA) device in 9 of 10 patients. In the other case transseptal puncture was required after detunnelisation before closure. Conclusions: Balloon assessment of PFOs enhances the understanding of their morphology and aids the identification of long tunnels. Detunnelisation using the same balloon facilitates the uncomplicated transcatheter closure of long tunnel PFOs in most patients. © 2008 Wiley-Liss, Inc.

To investigate the effect of endovascular stenting of aortic coarctation on biventricular function in adults during intermediate-term follow-up.21 patients (age 34 (10) years) were studied prospectively before and 14 (2) months after coarctation stenting from year 2002 to 2005. Biventricular function and blood pressure measurements were made. The post-stenting results were compared with pre-stenting values (group 1), with 22 age- and sex-matched post-surgical repair patients (group 2) and 30 normal controls (group 3).The peak systolic gradient across the coarctation site fell (55 (15) mm Hg to 18 (8) mm Hg, p0.001). Systolic, mean blood pressure and left ventricular (LV) mass dropped after stenting (p0.05 for all). LV long-axis function improved at intermediate-term follow-up (tissue Doppler imaging lateral and septal systolic and diastolic velocities and E/Em ratios: LSm, 6.5 (1.4) cm/s to 7.9 (1.7) cm/s; SSm, 5.8 (1.2) cm/s to 7.3 (1.6) cm/s; LEm, 8.1 (1.3) to 9.4 (2.3) cm/s; SEm, 6.7 (1.5) cm/s to 7.8 (1.9) cm/s; LE/Em, 11.2 (2.7) to 9.8 (2.8); SE/Em, 14.8 (5.3) to 11.8 (3.9); p0.05 for all). No significant difference in LV ejection fraction, conventional LV diastolic measurements (E, A, E/A ratio, IVRT and DT) was found after stenting. No significant deterioration of right ventricular function was seen in stented patients. Both post-stenting and post-surgical repair patients had poorer LV long-axis function than controls (p0.01 for all).Endovascular stenting of aortic coarctation resulted in medium-term LV mass regression and long-axis function improvement that may provide insight into long-term outcome of the stented patients. The results support aortic stenting in patients with anatomically suitable defects, given the additional benefit of avoiding cardiopulmonary bypass. The clinical significance of subclinical myocardial dysfunction in patients with stented or repaired coarctation warrants further studies.

Item does not contain fulltext BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS: Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

We sought to prove that device closure of atrial septal defect (ASD) in older patients not only improves cardiac function but also results in symptomatic relief by improving functional class.Atrial septal defect accounts for approximately 10% of all congenital cardiac defects. It is possible that ASD closure in older patients may derive benefits, though this is not well established. We therefore aim to prospectively assess the clinical status and functional class of older patients after transcatheter ASD closure.This was a prospective study of all patients age 40 years or more who underwent device closure of a secundum ASD between April 2004 and August 2006. Investigations including atrial and brain natriuretic peptide levels, electrocardiography, chest X-ray, transthoracic echocardiogram, 6-min walk test, and quality of life questionnaire were performed before and at 6 weeks and 1 year after the procedure.Twenty-three patients (median age 70 years, 13 women) had transcatheter device closure of ASD. Median ASD size was 18 mm (range 9 to 30 mm). Median pulmonary artery pressure was 22 mm Hg (range 12 to 27 mm Hg). At 1 year, New York Heart Association functional class improved (p = 0.004) in 16 patients with significant improvement in 6-min walk-test distance (p = 0.004) and physical (p = 0.002) as well as mental health score (p = 0.03). There were no major complications. One year following closure there was a significant change in left ventricular end-diastolic (p = 0.001) and end-systolic dimensions (p = 0.001) and also significant reduction in right ventricular end-diastolic dimension (p0.001).Our data demonstrated that ASD closure at advanced age results in favorable cardiac remodeling and improvement of functional class.

Jo-hannson et al wonder whether residual migraine burden might berelated to residual right-to-left shunting. The MIST trial was notpowered to assess this and was fully focused through its primary andsecondary end points on the possibility of migraine cessation orreduction in the implanted cohort. The degree of residual shuntingwas a tertiary end point of the study; however, moderate or largeresidual shunts were found in only 6% of patients.The real question arising from the MIST trial is why did PFOclosure for migraine alone prove relatively ineffective if PFO closurefor stroke routinely abolishes incidental migraine? First, manytreatments considered useful in observational registries become lessimpressive when tested in randomized, controlled trials. Second,migraine is a syndrome with no diagnostic test. Patients who havemigraine in the context of stroke normally have migraine of onlymodest severity. By comparison, the patients in the MIST trial werea cohort of severe long-term migraineurs who had failed to improveafter taking at least 2 prophylactic medications. For a sufferer withmoderate migraine, as typically seen in the stroke trials, PFO closuremight reduce the overall risk burden to below the average thresholdto trigger migraine. In the case of an intractable migraineur,however, other factors for migraine headache may be present. If weremove 1 of these factors by PFO closure, it is not surprising thatmigraine resolution after this intervention is rare.The best time to design a clinical trial has always been after thetrial has been completed, and in the case of the MIST trial, the useof a core echocardiographic laboratory would have prevented someof the conjecture surrounding the trial. It must be stressed, however,that the MIST trial was designed and powered to determine whetherPFO closure could effectively eradicate migraine headache, not todetermine whether residual shunts could be matched to residualmigraine. In this primary aspiration, it was ambitious, and ultimatelyunsuccessful, but the trial itself, with its unique sham-controlleddesign, was a success. The MIST trial will be remembered as the firstrandomized trial of PFO closure for migraine and the trial that pavedthe way for others to refine the patient group for whom this treatmentmight be most effective.

Background Novel oral anticoagulants (NOAC) are licensed for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). There has been no head-to-head comparison of these agents. The effect of these agents on global thrombotic status, and the relative effects of the different NOACs, is unknown. We aimed to assess the relative and absolute effect of NOACs and warfarin (VKA) on global thrombotic status. Methods We tested the thrombotic profile of 80 patients (61% male, age 72 ± 12 years) with newly diagnosed AF at baseline, and in response to different oral anticoagulant regimens. Patients were anticoagulated with apixaban (n = 20), dabigatran (n = 20), rivaroxaban (n = 20), or warfarin (n = 20). Assessment of thrombotic status was performed using the Global Thrombosis Test (GTT), an automated point-of-care test that assesses both platelet reactivity and endogenous thrombolysis from a native, non-anticoagulated blood sample. The time taken to form an occlusive thrombus under high shear stress (occlusion time, OT), and the time required to restore flow through endogenous thrombolysis (lysis time, LT) were measured at baseline and after being established on stable anticoagulation. Results Oral anticoagulation increased OT (419 ± 122s vs. 584 ± 153s; p = 0.00001), and reduced LT (1922 ± 820s vs. 1615 ± 936s; p = 0.01). Although all anticoagulant regimens prolonged OT, the relative prolongation of the OT from baseline was lower with apixaban than with other NOACs or VKA (apixaban 94 ± 135s, dabigatran 185 ± 149s, rivaroxaban 199 ± 104s, warfarin 184 ± 149s; p = 0.06). Apixaban reduced LT from baseline (2056 ± 568s vs. 1313 ± 885s; p = 0.003), but no reduction in LT was observed with other NOACs or VKA. Patients in the dabigatran group were younger than in other groups (65 ± 11; p = 0.006), but otherwise the groups were well matched for sex, diabetes, hypertension, platelet count, haematocrit and fibrinogen levels, and CHA²DS²VASc score. Conclusions All oral anticoagulants (OACs) prolong OT. Apixaban causes relatively less prolongation of OT than other OACs and also reduces LT. The relatively small increase in OT with apixaban compared to other OACs may explain the observed lower incidence of GI bleeds in large trials with this agent.

Objectives\ud This study sought to determine the relationship between blood viscosity and iron deficiency and their impact on symptoms and exercise function in adults with cyanotic congenital heart disease.\ud \ud Background\ud Iron deficiency is believed to raise whole blood viscosity in cyanotic congenital heart disease, although available data are inconsistent.\ud \ud Methods\ud Thirty-nine cyanotic adults were prospectively assessed for iron deficiency (transferrin saturation ≤5%), hyperviscosity symptoms, and exercise capacity. Same-day measurement of whole blood viscosity and hematocrit (Hct) adjusted viscosity (cells resuspended in autologous plasma to Hct of 45%) was performed at shear rates ranging from 0.277 s−1 to 128.5 s−1.\ud \ud Results\ud Viscosity did not differ between patients with iron deficiency (n = 14) and those without (n = 25). Whole blood viscosity correlated with Hct (r = 0.63, p < 0.001 at low shear and r = 0.84, p < 0.001 at high shear) but not with red blood cell size or iron indices. Hyperviscosity symptoms were independent of iron indices but directly correlated with increased Hct-adjusted viscosity (r = 0.41, p = 0.01). Exercise capacity did not differ in iron-deficient patients. However, peak oxygen consumption was higher in those with Hct ≥ 65% (12.6 ± 3.4 ml/kg/m2 vs. 9.8 ± 2.6 ml/kg/m2, mean ± SD, p = 0.036) despite higher whole blood viscosity in these same individuals (p < 0.01 for all shear rates).\ud \ud Conclusions\ud Iron deficiency is common in cyanotic adults but does not alter viscosity. Hyperviscosity symptoms are associated with a higher Hct-adjusted viscosity independent of cell size or iron stores. Higher Hct is associated with better exercise capacity. Further work to understand the origin of hyperviscosity symptoms is warranted.