Citations

SUMMARYUnderstanding the flow alteration in side branches during flow diversion treatment of cerebral aneurysms is important to prevent ischemic complications and improve device designs. Flow diverters were placed in the aorta of four rabbits crossing the origin of side arteries. Subject‐specific computational models were constructed from 3D angiographies and Doppler ultrasounds (DUSs). Flow simulations were run before and after virtually deploying the flow diverters, assuming distal resistances remained unchanged after treatment. All jailed arteries remained patent angiographically 8 weeks after treatment. The computational models estimated decreases compared to pretreatment in the mean flow rates between 2% and 20% and in peak flow rates between 5% and 36%. The major changes were observed during systole. Flow patterns did not exhibit recirculation zones before treatment. Implantation of the flow diverters altered the flow structure only locally near the device wires. No major recirculation regions were created or destroyed. Flow diverters seem safe with respect to perforator or side branch occlusion. Relatively small changes in flow rates through jailed arteries are expected, even for moderate to large degrees of coverage of their origins. These results seem consistent with previous clinical experiences where no or very few complications related to perforator occlusion have been reported.Copyright © 2014 John Wiley & Sons, Ltd.

Background— Coronary collateral flow is an alternative source of myocardial perfusion in patients with totally occluded coronary arteries. Clinical evaluation of collateral flow has been limited by the need of invasive measurements. We investigated whether noninvasive coronary computed tomographic angiography can evaluate the angiographic extent of coronary collateral flow. Methods and Results— We enrolled 325 coronary computed tomographic angiography cases with angiographically confirmed chronic total occlusion (median age, 63 years; men 83%). Transluminal attenuation gradient (TAG), which reflects the kinetics of contrast media in coronary artery, of an entire artery as well as of a distal vessel was assessed to evaluate the flow in entire vessel and distal vessel. TAGs were validated against visually assessed angiographic collateral connection and Rentrop grading. TAG of an entire artery increased consistently according to the angiographic extent of collateral flow ( P <0.001). Well-developed collaterals, defined by highest collateral connection and Rentrop grades (n=103), could be predicted by TAG of an entire artery (cutoff, ≥−7.6 Hounsfield units/10 mm; c -statistics, 0.72; sensitivity, 65%; specificity, 73%; positive predictive value, 52%; negative predictive value, 82%). TAG of a distal vessel could discriminate the antegrade (n=143) and retrograde (n=182) flows in distal artery (cutoff, 0.0 Hounsfield unit/10 mm; c -statistics, 0.88; sensitivity, 78%; specificity, 85%; positive predictive value, 87%; negative predictive value, 75%). Conclusions— TAG, an intracoronary attenuation-based analysis of coronary computed tomographic angiography, moderately reflected the functional extent and direction of collateral flow.

Background— Constrictive pericarditis is a potentially reversible cause of heart failure that may be difficult to differentiate from restrictive myocardial disease and severe tricuspid regurgitation. Echocardiography provides an important opportunity to evaluate for constrictive pericarditis, and definite diagnostic criteria are needed. Methods and Results— Patients with surgically confirmed constrictive pericarditis (n=130) at Mayo Clinic (2008–2010) were compared with patients (n=36) diagnosed with restrictive myocardial disease or severe tricuspid regurgitation after constrictive pericarditis was considered but ruled out. Comprehensive echocardiograms were reviewed in blinded fashion. Five principal echocardiographic variables were selected based on prior studies and potential for clinical use: (1) respiration-related ventricular septal shift, (2) variation in mitral inflow E velocity, (3) medial mitral annular e' velocity, (4) ratio of medial mitral annular e' to lateral e', and (5) hepatic vein expiratory diastolic reversal ratio. All 5 principal variables differed significantly between the groups. In patients with atrial fibrillation or flutter (n=29), all but mitral inflow velocity remained significantly different. Three variables were independently associated with constrictive pericarditis: (1) ventricular septal shift, (2) medial mitral e', and (3) hepatic vein expiratory diastolic reversal ratio. The presence of ventricular septal shift in combination with either medial e'≥9 cm/s or hepatic vein expiratory diastolic reversal ratio ≥0.79 corresponded to a desirable combination of sensitivity (87%) and specificity (91%). The specificity increased to 97% when all 3 factors were present, but the sensitivity decreased to 64%. Conclusions— Echocardiography allows differentiation of constrictive pericarditis from restrictive myocardial disease and severe tricuspid regurgitation. Respiration-related ventricular septal shift, preserved or increased medial mitral annular e' velocity, and prominent hepatic vein expiratory diastolic flow reversals are independently associated with the diagnosis of constrictive pericarditis.

Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. In-vitro studies have demonstrated a correlation between the magnitude and distribution of wall shear stress (WSS) and biological response of both endothelial cells and smooth muscle cells [1–3]. In elastase induced saccular aneurysms, low WSS (below 0.5 Pa) was found to have a correlation with altered expression of biological markers [4]. Localized regions of rapid aneurysm growth in-vivo have been shown to be associated with regions where WSS is below a critical value of 0.1 Pa [5]. Further, aspect ratio (AR), the ratio of the maximum diameter of the aneurysm to the width of the aneurysm neck, has been correlated with elevated risk of rupture [6]. The purpose of the current study is to explore the possibility of creating elastase induced aneurysms in rabbits with a range of aspect ratios (ratio of aneurysm height/neck) and evaluate the existence of a correlation between aspect ratio and WSS distribution. Aneurysms with ARs from 0.98 to 2.8 were created at the origin of the right common carotid artery (n = 30). Qualitative differences in WSS distribution were found in the high AR aneurysms (HARA) (AR>1.6) and low AR aneurysms (LARA) (AR<1.6) [7].

Summary Objective To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. Methods Randomized multicenter double‐blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period ( OLP ) to complete 2 years of postimplant follow‐up. Results All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was −37.9% in the active and −17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. Significance Responsive stimulation to the seizure focus reduced the frequency of partial‐onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial‐onset seizures.

IntroductionAdjudication of thousands of implantable cardioverter defibrillator (ICD)‐treated arrhythmia episodes is labor intensive and, as a result, is most often left undone. The objective of this study was to evaluate an automatic classification algorithm for adjudication of ICD‐treated arrhythmia episodes.MethodsThe algorithm uses a machine learning algorithm and was developed using 776 arrhythmia episodes. The algorithm was validated on 131 dual‐chamber ICD shock episodes from 127 patients adjudicated by seven electrophysiologists (EPs). Episodes were classified by panel consensus as ventricular tachycardia/ventricular fibrillation (VT/VF) or non‐VT/VF, with the resulting classifications used as the reference. Subsequently, each episode electrogram (EGM) data was randomly assigned to three EPs without the atrial lead information, and to three EPs with the atrial lead information. Those episodes were also classified by the automatic algorithm with and without atrial information. Agreement with the reference was compared between the three EPs consensus group and the algorithm.ResultsThe overall agreement with the reference was similar between three‐EP consensus and the algorithm for both with atrial EGM (94% vs 95%, P = 0.87) and without atrial EGM (90% vs 91%, P = 0.91). The odds of accurate adjudication, after adjusting for covariates, did not significantly differ between the algorithm and EP consensus (odds ratio 1.02, 95% confidence interval: 0.97–1.06).ConclusionsThis algorithm performs at a level comparable to an EP panel in the adjudication of arrhythmia episodes treated by both dual‐ and single‐chamber ICDs. This type of algorithm has the potential for automated analysis of clinical ICD episodes, and adjudication of EGMs for research studies and quality analyses.

AbstractNeuromyelitis optica (NMO) is a disabling autoimmune astrocytopathy characterized by typically severe and recurrent attacks of optic neuritis and longitudinally extensive myelitis. Until recently, NMO was considered an acute aggressive variant of multiple sclerosis (MS), despite the fact that early studies postulated that NMO and MS may be two distinct diseases with a common clinical picture. With the discovery of a highly specific serum autoantibody (NMO‐IgG), Lennon and colleagues provided the first unequivocal evidence distinguishing NMO from MS and other central nervous system (CNS) inflammatory demyelinating disorders. The target antigen of NMO‐IgG was confirmed to be aquaporin‐4 (AQP4), the most abundant water channel protein in the CNS, mainly expressed on astrocytic foot processes at the blood–brain barrier, subpial and subependymal regions. Pathological studies demonstrated that astrocytes were selectively targeted in NMO as evidenced by the extensive loss of immunoreactivities for the astrocytic proteins, AQP4 and glial fibrillary acidic protein (GFAP), as well as perivascular deposition of immunoglobulins and activation of complement even within lesions with a relative preservation of myelin. In support of these pathological findings, GFAP levels in the cerebrospinal fluid (CSF) during acute NMO exacerbations were found to be remarkably elevated in contrast to MS where CSF‐GFAP levels did not substantially differ from controls. Additionally, recent experimental studies showed that AQP4 antibody is pathogenic, resulting in selective astrocyte destruction and dysfunction in vitro, ex vivo and in vivo. These findings strongly suggest that NMO is an autoimmune astrocytopathy where damage to astrocytes exceeds both myelin and neuronal damage. This chapter will review recent neuropathological studies that have provided novel insights into the pathogenic mechanisms, cellular targets, as well as the spectrum of tissue damage in NMO.

Abstract Glaucoma is a leading cause of blindness in the United States affecting as many as 2.2 million Americans. All current glaucoma treatment strategies aim to reduce intraocular pressure, even in patients with normal tension glaucoma. Typically, this is accomplished by reducing the rate of aqueous flow by limiting aqueous production or enhancing drainage using drugs and surgery. Whereas these strategies are effective in diminishing vision loss, some patients continue to lose vision and many discontinue use of their medications because of undesirable side effects. Drugs known to be effective in altering conventional outflow have for the most part been abandoned from modern clinical practice due to undesirable side effects. Identification of new drugs that could enhance conventional outflow, would offer additional options in the treatment of glaucoma and ocular hypertension. To this end, our laboratory has recently uncovered a novel pathway for regulation of conventional outflow by the ciliary body. This pathway is dependent on soluble adenylyl cyclase, an enzyme that catalyzes the generation of cyclic adenosine 3′,5′ monophosphate (cAMP) in response to bicarbonate.