European experience with the second-generation Edwards SAPIEN XT transcatheter heart valve in patients with severe aortic stenosis: 1-year outcomes from the SOURCE XT Registry

OBJECTIVES The SOURCE XT Registry (Edwards SAPIEN XT Aortic Bioprosthesis Multi-Region Outcome Registry) assessed the use and clinical outcomes with the SAPIEN XT (Edwards Lifesciences, Irvine, California) valve in the real-world setting. BACKGROUND Transcatheter aortic valve replacement is an established treatment for high-risk/inoperable patients with severe aortic stenosis. The SAPIEN XT is a balloon-expandable valve with enhanced features allowing delivery via a lower profile sheath. METHODS The SOURCE XT Registry is a prospective, multicenter, post-approval study. Data from 2,688 patients at 99 sites were analyzed. The main outcome measures were all-cause mortality, stroke, major vascular complications, bleeding, and pacemaker implantations at 30-days and 1 year post-procedure. RESULTS The mean age was 81.4 ± 6.6 years, 42.3% were male, and the mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 20.4 ± 12.4%. Patients had a high burden of coronary disease (44.2%), diabetes (29.4%), renal insufficiency (28.9%), atrial fibrillation (25.6%), and peripheral vascular disease (21.2%). Survival was 93.7% at 30 days and 80.6% at 1 year. At 30-day follow-up, the stroke rate was 3.6%, the rate of major vascular complications was 6.5%, the rate of life-threatening bleeding was 5.5%, the rate of new pacemakers was 9.5%, and the rate of moderate/severe paravalvular leak was 5.5%. Multivariable analysis identified nontransfemoral approach (hazard ratio [HR]: 1.84; p < 0.0001), renal insufficiency (HR: 1.53; p < 0.0001), liver disease (HR: 1.67; p = 0.0453), moderate/severe tricuspid regurgitation (HR: 1.47; p = 0.0019), porcelain aorta (HR: 1.47; p = 0.0352), and atrial fibrillation (HR: 1.41; p = 0.0014), with the highest HRs for 1-year mortality. Major vascular complications and major/life-threatening bleeding were the most frequently seen complications associated with a significant increase in 1-year mortality. CONCLUSIONS The SOURCE XT Registry demonstrated appropriate use of the SAPIEN XT THV in the first year post-commercialization in Europe. The safety profile is sustained, and clinical benefits have been established in the real-world setting. (SOURCE XT Registry; NCT01238497).

The correlation of epicardial adipose tissue on postmortem CT with coronary artery stenosis as determined by autopsy

The goal of this study was to assess whether epicardial and paracardial adipose tissue volumes, as determined by computed tomography (CT), correlate with coronary artery stenosis as determined by autopsy. The postmortem CT data and autopsy findings of 116 adult human decedents were retrospectively compared. Subjects were classified into three groups according to their degree of coronary artery stenosis: ≥50, <50%, and no stenosis. Epicardial and paracardial adipose tissue volumes were calculated based on manual segmentation after threshold based masking. In addition, epicardial adipose tissue thickness was measured using a caliper. All three parameters (thickness of epicardial fat and volumes of both epicardial and paracardial fat) were compared among the three groups and correlated with the degree of coronary artery stenosis. The group with no coronary artery stenosis showed the lowest mean values of epicardial adipose tissue volume, while the coronary artery stenosis ≥50 % group showed the highest volume. All measured variables (thickness of epicardial fat and volumes of both epicardial and paracardial fat) correlated significantly with the grade of coronary artery stenosis, even after controlling for BMI, however, epicardial adipose tissue volume exhibited the strongest correlation. This study reveals that there is an association between the degree of coronary artery stenosis and the amount of epicardial fat tissue: The larger the volume of epicardial fat, the higher the degree of coronary artery stenosis.

Internal and external effects on cognition: Evidence from memory training in very preterm-born children and cognition in patients with carotid artery stenosis before and after treatment

The present synopsis aims to integrate one study about memory training in very preterm-born children and two studies about cognition in patients with carotid artery stenosis before and after treatments. Preterm-born children are at increased risk of cognitive deficits and behavioural problems compared with peers born at term. This thesis determined whether memory training would improve cognitive functions in school-age very preterm-born children. Memory strategy training produced significant improvements in trained and non-trained cognitive functions; a core working memory training revealed significant effects on short-term memory and working memory tasks. Six months after training, children in both training groups showed better working memory performance than children in the waiting control group. This is evidence that memory training – an external influence on cognition – induces plastic changes in very preterm-born children. Patients with carotid artery stenosis are known to be at increased risk of cognitive impairment. We showed that patients with symptomatic or asymptomatic carotid artery stenosis were at higher risk for cognitive deficits than expected in a normative sample. This thesis seeks to link cognitive plasticity to internal factors like carotid stenosis. An external factor, which influences blood flow to the brain is the nature of the carotid artery stenosis treatment. Research on the effects of carotid artery stenosis treatment on cognition has produced inconsistent results. We found significant improvement in frontal lobe functions, visual memory and motor speed one year after treatment independent of the treatment type (best medical treatment, carotid artery stenting, carotid artery endarterectomy); providing evidence for ‘treatment-induced’ cognitive plasticity. Baseline performance was negatively associated with improvement in various cognitive functions after training in very preterm-born children and after treatment in patients with carotid artery stenosis. The present synopsis aims to integrate these findings into the current and relevant literature, and discuss consequences as well as methodological considerations resulting from the studies constituting the thesis at hand.

Is the sedimentation sign associated with spinal stenosis surgical treatment effect in SPORT?

STUDY DESIGN Subgroup analysis of the lumbar spinal stenosis (LSS) without degenerative spondylolisthesis diagnostic cohort of the Spine Patient Outcomes Research Trial multicenter randomized clinical trial with a concurrent observational cohort. OBJECTIVE To determine if sedimentation sign on magnetic resonance image can help with LSS treatment decisions. SUMMARY OF BACKGROUND DATA LSS is one of the most common reasons for surgery in the US elderly, but there is a dearth of reliable diagnostic tools that give a clear indication for surgery. Recent studies have suggested that positive sedimentation sign on magnetic resonance image may be a possible prognostic indicator. METHODS All patients with LSS in both the randomized and observational cohorts had imaging-confirmed stenosis, were surgical candidates, and had neurogenic claudication for at least 12 weeks prior to enrollment. Patients were categorized as "mild," "moderate," or "severe" according to stenosis severity. Of the 654 patients with LSS enrolled in Spine Patient Outcomes Research Trial, complete T2-weighted axial and sagittal digitized images of 115 patients were available for retrospective review. An independent orthopedic spine surgeon evaluated these deidentified Digital Imaging and Communications in Medicine files for the sedimentation sign. RESULTS Sixty-six percent (76/115) of patients were found to have a positive sedimentation sign. Those with a positive sedimentation sign were more likely to have stenosis at L2-L3 (33% vs. 10% P=0.016) or L3-L4 76% vs. 51%, P=0.012), and to have severe (72% vs. 33%, P<0.0001) central stenosis (93% vs. 67% P<0.001) at 2 or more concurrent levels (57% vs. 18%, P=0.01). In multivariate models, the surgical treatment effect was significantly larger in the positive sedimentation sign group for Oswestry Disability Index (-16 vs. -7; P=0.02). CONCLUSION A positive sedimentation sign was associated with a small but significantly greater surgical treatment effect for Oswestry Disability Index in patients with symptomatic LSS, after adjusting for other demographic and imaging features. These findings suggest that positive sedimentation sign may potentially be a useful adjunct to help guide an informed treatment choice regarding surgery for LSS. LEVEL OF EVIDENCE 2.

Patient outcomes after laminotomy, hemilaminectomy, laminectomy and laminectomy with instrumented fusion for spinal canal stenosis: a propensity score-based study from the Spine Tango registry.

PURPOSE To compare patient outcomes and complication rates after different decompression techniques or instrumented fusion (IF) in lumbar spinal stenosis (LSS). METHODS The multicentre study was based on Spine Tango data. Inclusion criteria were LSS with a posterior decompression and pre- and postoperative COMI assessment between 3 and 24 months. 1,176 cases were assigned to four groups: (1) laminotomy (n = 642), (2) hemilaminectomy (n = 196), (3) laminectomy (n = 230) and (4) laminectomy combined with an IF (n = 108). Clinical outcomes were achievement of minimum relevant change in COMI back and leg pain and COMI score (2.2 points), surgical and general complications, measures taken due to complications, and reintervention on the index level based on patient information. The inverse propensity score weighting method was used for adjustment. RESULTS Laminotomy, hemilaminectomy and laminectomy were significantly less beneficial than laminectomy in combination with IF regarding leg pain (ORs with 95% CI 0.52, 0.34-0.81; 0.25, 0.15-0.41; 0.44, 0.27-0.72, respectively) and COMI score improvement (ORs with 95% CI 0.51, 0.33-0.81; 0.30, 0.18-0.51; 0.48, 0.29-0.79, respectively). However, the sole decompressions caused significantly fewer surgical (ORs with 95% CI 0.42, 0.26-0.69; 0.33, 0.17-0.63; 0.39, 0.21-0.71, respectively) and general complications (ORs with 95% CI 0.11, 0.04-0.29; 0.03, 0.003-0.41; 0.25, 0.09-0.71, respectively) than laminectomy in combination with IF. Accordingly, the likelihood of required measures was also significantly lower after laminotomy (OR 0.28, 95% CI 0.17-0.46), hemilaminectomy (OR 0.28, 95% CI 0.15-0.53) and after laminectomy (OR 0.39, 95% CI 0.22-0.68) in comparison with laminectomy with IF. The likelihood of a reintervention was not significantly different between the treatment groups. DISCUSSION As already demonstrated in the literature, decompression in patients with LSS is a very effective treatment. Despite better patient outcomes after laminectomy in combination with IF, caution is advised due to higher rates of surgical and general complications and consequent required measures. Based on the current study, laminotomy or laminectomy, rather than hemilaminectomy, is recommendable for minimum relevant pain relief.

Superior outcomes of decompression with an interlaminar dynamic device versus decompression alone in patients with lumbar spinal stenosis and back pain: a cross registry study.

INTRODUCTION Surgical decompression for lumbar spinal stenosis (LSS) has been associated with poorer outcomes in patients with pronounced low back pain (LBP) as compared to patients with predominant leg pain. This cross registry study assessed potential benefits of the interlaminar coflex® device as an add-on to bony decompression alone. METHODS Patients with lumbar decompression plus coflex® (SWISSspine registry) were compared with decompressed controls (Spine Tango registry). Inclusion criteria were LSS and a preoperative back pain level of ≥5 points. 1:1 propensity score-based matching was performed. Outcome measures were back and leg pain relief, COMI score improvement, patient satisfaction, complication, and revision rates. RESULTS 50 matched pairs without residual significant differences but age were created. At the 7-9 months follow-up interval the coflex® group had higher back (p=0.014) and leg pain relief (p<0.001) and COMI score improvement (p=0.029) than the decompression group. Patient satisfaction was 90% in both groups. No revision was documented in the coflex® and one in the decompression group (2.0%). DISCUSSION In the short-term, lumbar decompression with coflex® compared with decompression alone in patients with LSS and pronounced LBP at baseline is a safe and effective treatment option that appears beneficial regarding clinical and functional outcomes. However, residual confounding of non-measured covariables may have partially influenced our findings. Also, despite careful inclusion and exclusion of cases the cross registry approach introduces a potential for selection bias that we could not totally control for and that makes additional studies necessary.

Hyperoxia Exacerbates Myocardial Ischemia in the Presence of Acute Coronary Artery Stenosis in Swine.

BACKGROUND Current guidelines limit the use of high oxygen tension after return of spontaneous circulation after cardiac arrest, focusing on neurological outcome and mortality. Little is known about the impact of hyperoxia on the ischemic heart. Oxygen is frequently administered and is generally expected to be beneficial. This study seeks to assess the effects of hyperoxia on myocardia oxygenation in the presence of severe coronary artery stenosis in swine. METHODS AND RESULTS In 22 healthy pigs, we surgically attached a magnetic resonance compatible flow probe to the left anterior descending coronary artery (LAD). In 11 pigs, a hydraulic occluder was inflated distal to the flow probe. After increasing PaO2 to >300 mm Hg, LAD flow decreased in all animals. In 8 stenosed animals with a mean fractional flow reserve of 0.64±0.02, hyperoxia resulted in a significant decrease of myocardial signal intensity in oxygenation-sensitive cardiovascular magnetic resonance images of the midapical segments of the LAD territory. This was not seen in remote myocardium or in the other 8 healthy animals. The decreased signal intensity was accompanied by a decrease in circumferential strain in the same segments. Furthermore, ejection fraction, cardiac output, and oxygen extraction ratio declined in these animals. Changing PaCO2 levels did not have a significant effect on any of the parameters; however, hypercapnia seemed to nonsignificantly attenuate the hyperoxia-induced changes. CONCLUSIONS Ventilation-induced hyperoxia may decrease myocardial oxygenation and lead to ischemia in myocardium subject to severe coronary artery stenosis.

Early identification of symptomatic aortic stenosis using echocardiographic data

Background: Heart failure (CHF) is the most frequent and prognostically severe symptom of aortic stenosis (AS), and the most common indication for surgery. The mainstay of treatment for AS is aortic valve replacement (AVR), and the main indication for an AVR is development of symptomatic disease. ACC/AHA guidelines define severe AS as an aortic valve area (AVA) ≤1cm², but there is little data correlating echocardiogram AVA with the onset of symptomatic CHF. We evaluated the risk of developing CHF with progressively decreasing echocardiographic AVA. We also compared echocardiographic AVA with Jet velocity (V2) and indexed AVA (AVAI) to assess the best predictor of development of symptomatic CHF.^ Methods and Results: This retrospective cohort study evaluated 518 patients with asymptomatic moderate or severe AS from a single community based cardiology practice. A total of 925 echocardiograms were performed over an 11-year period. Each echocardiogram was correlated with concurrent clinical assessments while the investigator was blinded to the echocardiogram severity of AS. The Cox Proportional hazards model was used to analyze the relationship between AVA and the development of CHF. The median age of patients at entry was 76.1 years, with 54% males. A total of 116 patients (21.8%) developed new onset CHF during follow-up. Compared to patients with AVA >1.0cm², patients with lower AVA had an exponentially increasing risk of developing CHF for each 0.2cm² decrement in AVA, becoming statistically significant only at an AVA less than 0.8 cm². Also, compared to V2 and AVAI, AVA added more information to assessing risk for development of CHF (p=0.041). ^ Conclusion: In patients with normal or mildly impaired LVEF, the risk of CHF rises exponentially with decreasing valve area and becomes statistically significant after AVA falls below 0.8cm². AVA is a better predictor of CHF when compared to V2 or AVAI.^

Carotid endarterectomy relieves pulsatile tinnitus associated with severe ipsilateral carotid stenosis

Objectives. Pulsatile tinnitus is a rare and often disabling condition. Pulsatile tinnitus sometimes occurs in patients with severe atherosclerotic carotid stenosis. It is uncertain whether carotid endarterectomy (CEA) relieves pulsatile tinnitus in patients with severe carotid stenosis. Design, Materials and Methods. This is a retrospective study of 14 patients with pulsatile tinnitus who underwent CEA. Demographic and clinical features and pre-operative duplex results were recorded. Operative results in this group were assessed. Results. CEA relieved symptoms of pulsatile tinnitus in 10 out of 14 cases (70%). Of 10 patients that had lateralisable tinnitus and ipsilateral surgery, 9 (90%) reported symptomatic improvement. Conclusions. CEA is effective in improving pulsatile tinnitus in patients with unilateral symptoms and severe ipsilateral carotid stenosis.

Local delivery of the KCa3.1 blocker, TRAM-34, prevents acute angioplasty-induced coronary smooth muscle phenotypic modulation and limits stenosis

Objective-We previously demonstrated that upregulation of intermediate-conductance Ca2+ -activated K+ channels (KCa 3.1) is necessary for mitogen-induced phenotypic modulation in isolated porcine coronary smooth muscle cells (SMCs). The objective of the present study was to determine the role of KCa3.1 in the regulation of coronary SMC phenotypic modulation in vivo using a swine model of postangioplasty restenosis. Methods and Results-Balloon angioplasty was performed on coronary arteries of swine using either noncoated or balloons coated with the specific KCa3.1 blocker TRAM-34. Expression of KCa3.1, c-jun, c-fos, repressor element-1 silencing transcription factor (REST), smooth muscle myosin heavy chain (SMMHC), and myocardin was measured using qRT-PCR in isolated medial cells 2 hours and 2 days postangioplasty. KCa3.1, c-jun, and c-fos mRNA levels were increased 2 hours postangioplasty, whereas REST expression decreased. SMMHC expression was unchanged at 2 hours, but decreased 2 days postangioplasty. Use of TRAM-34 coated balloons prevented KCa3.1 upregulation and REST downregulation at 2 hours, SMMHC and myocardin downregulation at 2 days, and attenuated subsequent restenosis 14 and 28 days postangioplasty. Immunohistochemical analysis demonstrated corresponding changes at the protein level. Conclusion-Blockade of KCa3.1 by delivery of TRAM-34 via balloon catheter prevented smooth muscle phenotypic modulation and limited subsequent restenosis. © 2008 American Heart Association, Inc.

Fluid dynamics and platelet deposition in a model arterial stenosis

The objective of this study was to gain further understanding and elucidation of the fluid dynamic factors and flow-induced mechanisms of the thrombogenic process of platelet deposition onto, and possible subsequent embolization from, the walls of an arterial stenosis. This has been accomplished by measurement of the axial dependence of platelet deposition within a modeled arterial stenosis for a transitional flow and a completely laminar flow field. The stenotic region of the model was collagen-coated to simulate a damaged endothelial lining of an artery. Fluid dynamics within a stenosis was studied using qualitative flow visualization, and was further compared to the in vitro platelet deposition studies. Normalized platelet density (NPD) measurements indicate decreased levels of NPD in the high shear throat region of the stenosis for a Reynolds number of 300 and a drastic increase in NPD at the throat for a Reynolds number of 175. This study provides further understanding of the flow dynamic effects on thrombus development within a stenosis. ^