W. Stewart Hillis

Migraine Intervention With STARFlex Technology (MIST) Trial A Prospective, Multicenter, Double-Blind, Sham-Controlled Trial to Evaluate the Effectiveness of Patent Foramen Ovale Closure With STARFlex Septal Repair Implant to Resolve Refractory Migraine Headache

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.

BioSTAR Evaluation STudy (BEST) A Prospective, Multicenter, Phase I Clinical Trial to Evaluate the Feasibility, Efficacy, and Safety of the BioSTAR Bioabsorbable Septal Repair Implant for the Closure of Atrial-Level Shunts

Background— The use of permanent synthetic implants to close atrial septal defects (ASD) and patent foramen ovale (PFO) has a number of limitations, including late complications and the limiting of transeptal access to the left heart should it be required for the later treatment of acquired heart disease. BioSTAR is a novel, bioabsorbable, atrial septal repair implant. This phase I pilot study evaluates the feasibility, safety, and effectiveness of BioSTAR for the first time in humans. Methods and Results— We conducted a prospective, open-label, multicenter clinical study in 58 patients aged 28 to 68 years who had a clinically significant ASD or PFO. Percutaneous shunt closure was undertaken with the BioSTAR septal repair implant. Successful device implantation was achieved in 57 (98%) of 58 patients. Closure at 30 days and 6 months, assessed by contrast transthoracic echocardiography, was 48 (92%) of 52 and 54 (96%) of 56, respectively. There was no evidence of a clinically significant response to the device. Transient atrial arrhythmia occurred in 5 patients after implantation. No major safety issues were observed. Conclusions— This study demonstrates the feasibility, safety, and effectiveness of BioSTAR for the closure of ASD and PFO in humans with a high rate of early and complete shunt closure. BioSTAR is a novel septal repair implant designed to provide biological closure of atrial-level defects using the patient’s natural healing response. Because 90% to 95% of the implant is absorbed and replaced with healthy native tissue, future access to the left atrium may be achieved.

A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI).

Objectives The aim of this study was to assess whether deferred stenting might reduce no-reflow and salvage myocardium in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Background No-reflow is associated with adverse outcomes in STEMI. Methods This was a prospective, single-center, randomized, controlled, proof-of-concept trial in reperfused STEMI patients with ≥1 risk factors for no-reflow. Randomization was to deferred stenting with an intention-to-stent 4 to 16 h later or conventional treatment with immediate stenting. The primary outcome was the incidence of no-/slow-reflow (Thrombolysis In Myocardial Infarction ≤2). Cardiac magnetic resonance imaging was performed 2 days and 6 months after myocardial infarction. Myocardial salvage was the final infarct size indexed to the initial area at risk. Results Of 411 STEMI patients (March 11, 2012 to November 21, 2012), 101 patients (mean age, 60 years; 69% male) were randomized (52 to the deferred stenting group, 49 to the immediate stenting). The median (interquartile range [IQR]) time to the second procedure in the deferred stenting group was 9 h (IQR: 6 to 12 h). Fewer patients in the deferred stenting group had no-/slow-reflow (14 [29%] vs. 3 [6%]; p = 0.006), no reflow (7 [14%] vs. 1 [2%]; p = 0.052) and intraprocedural thrombotic events (16 [33%] vs. 5 [10%]; p = 0.010). Thrombolysis In Myocardial Infarction coronary flow grades at the end of PCI were higher in the deferred stenting group (p = 0.018). Recurrent STEMI occurred in 2 patients in the deferred stenting group before the second procedure. Myocardial salvage index at 6 months was greater in the deferred stenting group (68 [IQR: 54% to 82%] vs. 56 [IQR: 31% to 72%]; p = 0.031]. Conclusions In high-risk STEMI patients, deferred stenting in primary PCI reduced no-reflow and increased myocardial salvage. (Deferred Stent Trial in STEMI; NCT01717573)

Fragmin in Unstable Angina Pectoris or in Non-Q-Wave Acute Myocardial Infarction (the FRIC Study)

The safety and efficacy of weight-adjusted, low-molecular-weight heparin (dalteparin) was compared with that of unfractionated heparin during 6 days of treatment in 1,482 patients with unstable angina or non-Q-wave myocardial infarction. Dalteparin, at a lower dose, was compared with placebo during the following 39 days. No significant outcome difference was found between the 2 treatment regimens in the unblinded phase (days 1-6). Between days 6-45 the rates of death, myocardial infarction, and recurrence of angina were comparable between the active treatment and placebo groups. The results suggest that twice-daily administration of subcutaneous dalteparin may be an effective and safe alternative to unfractionated heparin during the acute phase of unstable coronary artery disease. Prolonged treatment with dalteparin at a lower once-daily dose did not confer any additional benefit over aspirin (75-165 mg) alone.

The Ergoreflex in patients with chronic stable heart failure

BACKGROUND The main symptoms of chronic heart failure are breathlessness and fatigue on exertion. Abnormalities of skeletal muscle cause early metabolic distress on exercise, with resultant ergoreceptor stimulation causing increased ventilation. The aim of this study is to determine the extent of enhanced ergoreflex activity in chronic heart failure in the leg. METHODS Ten patients with chronic stable heart failure (New York Heart Association class II-III) and nine healthy age-matched controls performed two bouts of ankle dorsiflexion. On one occasion a cuff was inflated round the thigh to suprasystolic levels for 3 min immediately post-exercise: regional circulatory occlusion. Recovery with regional circulatory occlusion was compared to recovery without it. RESULTS Systolic and diastolic blood pressure and ventilation were higher after 3 min post-exercise regional circulatory occlusion than after 3 min control recovery in the patient group (184+/-13.3 vs. 165+/-12.5 mm Hg, P<0.01, 94+/-4.7 vs. 86+/-3.5 mm Hg, P<0.05, 9.8+/-0.7 vs. 7.9+/-0.36 l/min, P<0.01). Systolic and diastolic blood pressure were higher after post-exercise regional circulatory occlusion than after control recovery in the control group (149+/-7.8 vs. 138+/-5.7 mm Hg, P<0.01, 86+/-3.3 vs. 82+/-2.5 mm Hg, P<0.05), but this was not the case for ventilation (8.1+/-0.62 vs. 8.1+/-0.62 l/min). Ergoreflex activity was greater in the patient group than in the controls for systolic blood pressure (91 vs. 48%, P<0.001), diastolic blood pressure (86 vs. 49%, P<0.05) and ventilation (39 vs. -1%, P<0.05). CONCLUSIONS Ergoreceptor stimulation contributes to an increased ventilation and blood pressure response to leg exercise in chronic heart failure patients, perhaps contributing to dyspnoea and exercise limitation. Peripheral factors such as skeletal muscle abnormalities contribute to the pathogenesis of symptoms in chronic heart failure.

An influence of variation in the aldosterone synthase gene (CYP11B2) on corticosteroid responses to ACTH in normal human subjects.

OBJECTIVE Previous evidence suggests that the efficiency of 11β‐hydroxylase is at least partly heritable and also that it may be mildly impaired in essential hypertension. In both cases, assessment of activity was based on the response of 11‐deoxycorticosterone (DOC) and 11‐deoxycortisol to ACTH. The gene (CYP11B1) coding for this enzyme is highly homologous with and lies a relatively short distance downstream from the gene coding for aldosterone synthase (CYP11B2) on chromosome 8. Two polymorphisms of CYP11B2 have been described. The first involves a change of −344C to T in a putative steroidogenic factor‐1 (SF‐1) binding site and the other, the intron conversion, an exchange of intron 2 for that of CYP11B1. These polymorphisms are in linkage dysequilibrium. Their effects on 11β‐hydroxylation were studied.

Reactive hyperemia: an index of the significance of coronary stenoses.

Coronary arterial stenosis of varying severity and length were created in open-chest dogs. The reactive hyperemic responses (RHR) to 15 second occlusions were used to produce flow increases and judge the physiological significance of the narrowings. RHR are sensitive indices of functional impairment when resting flow is unchanged. It was demonstrated that the length as well as the severity is important in assessing physiological significance by evaluation of narrowings 3 to 9 mm. long.

Hemodynamic and coronary effects of intravenous eletriptan, a 5HT1B/1D‐receptor agonist

To investigate the systemic, pulmonary, and coronary artery effects of eletriptan, a new 5HT1B/1D‐agonist in patients undergoing cardiac catheterization.

The prevalence of left ventricular hypertrophy in elite professional footballers

BACKGROUND We evaluated the prevalence of left ventricular hypertrophy in elite footballers compared with sedentary controls. A total of 141 elite male professional footballers and 32 healthy sedentary controls were studied. Echocardiographic and demographic variables were compared between groups by unpaired t-test. RESULTS The prevalence of left ventricular hypertrophy with maximal wall thickness values out with the normal range (>12 mm) was noted. Footballers were significantly younger than controls (20.9 vs. 24.3 years, P<0.005: 95% CI (-5.2, -1.73)) but there were no significant differences in height, weight or body surface area between the groups. Each of inter-ventricular septum (10.4 vs. 9.1 mm, P<0.0001; 95% CI (0.88, 1.72)), posterior wall (9.2 vs. 8.5 mm, P<0.01; 95% CI (0.22, 1.21)), left ventricular cavity (systolic and diastolic) (34.5 vs. 28.4 mm, P<0.0001; 95% CI (4.31, 7.76) in systole; 50.1 vs. 48.2 mm, P<0.05; 95% CI (0.15, 3.74) in diastole), aortic root size (29.1 vs. 27.8 mm, P<0.05; 95% CI (0.03,2.49)) and left ventricular mass index (112 vs. 89 g/m2, P<0.0001; 95% CI (14.4, 32.1)) were significantly greater in footballers than in controls. Absolute left ventricular wall thickness >12 mm was present in 17 footballers (12%) (range 13-15 mm) and in no controls. CONCLUSIONS Elite professional footballers have increased cardiac dimensions compared with healthy controls. The prevalence of absolute wall thicknesses out with the normal range is relatively high.

Transcatheter closure of a ventricular septal defect resulting from knife stabbing using the Amplatzer muscular VSD occluder

We report for the first time the transcatheter closure of a traumatic ventricular septal defect (VSD) with the Amplatzer muscular VSD occluder in a 34‐year‐old man who had been stabbed through the heart. After his initial life‐saving surgery to relieve tamponade, control bleeding, and repair the lacerated right ventricle, the risks and difficulties of subsequent open heart surgery were felt to favor transcatheter closure. We review other reports of transcatheter closure of traumatic VSD.