Meissner, Irene

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Introduction: The long term effectiveness of preventive intracranial treatment of unruptured aneurysms for hemorrhage and aneurysm-related morbidity and mortality has been hypothesized. No randomized trial has been done. Propensity adjusted comparison within The International Study of Unruptured Intracranial Aneurysms was undertaken to compare long-term effectiveness. Hypothesis: The purpose of this analysis was to compare the long-term outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort, 471 were in the endovascular cohort and 1917 patients were in the surgical cohort. The cohorts were followed for a median follow-up of 9.2 years. Outcomes were determined prospectively and with central review. The data were grouped together and analyzed to determine treatment decisions. Comparison of outcomes was done using covariate adjustment and using propensity analysis where equivalent probability groups were constructed. Similar main predictors of treatment and outcome were observed. Analysis of hemorrhage, mortality and short-term and long-term morbidity and mortality were assessed. Risk-benefit ratios were also calculated. Results: Significant differences in baseline variables between treatment and observed patients were aneurysm size, symptoms, age, prior SAH or not group, geographical region, family history, hypertension and myocardial infarction history. The results show comparability of groups using the patient propensity-based score subset. Using the propensity score method, the results showed a benefit in prevention of hemorrhage by surgery and endovascular treatment versus observation (p<.01). No difference was found between endovascular versus surgery. However when procedure-related outcomes are included, no significant difference at 1 year, 5 years or 10 years in the combined aneurysm or procedure related endpoint was evident between cohorts. Conclusions: Propensity score matching to achieve comparability resulted in balanced groups. Comparison of long-term results showed that intervention demonstrated a benefit in reducing hemorrhage risk. However, peri-procedural risk negates any short-term benefit for 10 years.

Introduction: Mortality in patients with unruptured intracranial aneurysm (UIA) is significantly higher than the general population. However a minority of the deaths are due to subarachnoid hemorrhage. Hypothesis: There are differential characteristics of patients that might predict specific causes of death that would be informative in counseling patients about aneurysm risk. Methods: 4059 patients with UIA who were enrolled prospectively between 1991 and 1998 were followed by 61 medical centers in North America, Canada, and Europe. Patients have at least one UIA, which may or may not be symptomatic. Patients were Rankin grade 1 or 2 at enrollment. Patients were followed annually from enrollment to 2007. For patients who died a death certificate search was done and information was requested from local physicians and other contacts. A National Death Index search in 2008 determined cases who died and cause of death. Foreign centers also did a national search where possible. Patients who died before 30 days post treatment or lost to follow up before 30 days post enrollment were excluded. Results: Twenty-five percent of patients died during follow-up. The life expectancy was significantly less than age-, sex-, and country-matched expected estimates. Among the total of 4004 patients with UIA who survived 30 days after enrollment, 2331 were treated and 1673 were not. There were 965 deaths after 30 days after treatment, of which 320 died from vascular disease (252 died from non-SAH vascular disease), 114 died from respiratory tract disease, 255 died from cancer, and the rest died of other or unknown reasons. Predictors of SAH death were aneurysm size, site, age and convulsive disorders at enrollment. Factors related to vascular death were UIA treatment, age, gender, race, hypertension, Rankin at discharge and diminishing influence of aneurysm characteristics over time. Respiratory deaths were related to treatment, race, smoking, age, initial Rankin and presentation with convulsive disorder. Cancer deaths were related to gender, race, smoking and age. Conclusions: In patients with UIA, an assessment of risk for death underscores the importance of age, race and gender and several modifiable risk factors. Patient management should include not only aneurysm rupture prevention but also modification of smoking and hypertension.

Introduction: Quality of life changes can occur following procedural interventions and subarachnoid hemorrhage in unruptured intracranial aneurysms (UIA). The International Study of Unruptured Intracranial Aneurysms conducted quality of life assessment using the Mini-Mental State Exam, Rankin Score, and Barthel Index at baseline and the Telephone Interview Cognitive Status Exam (TICS), Rankin Score, and Barthel Index at follow-up. Hypothesis: The purpose of this analysis was to compare the 1 year and 5 year outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treated and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort and 2388 in the treated cohort. The cohorts were followed annually with measures of neurological status, Rankin Scale, Barthel Index and cognition (TICS). Outcomes were determined prospectively. Comparison of outcomes was done using continuous and categorical data. Covariate adjustment was done using general linear models. Stratified analysis was done by Rankin Score at the time of follow-up. Results: The percent of patients with a Barthel Index score of less than 60 at 1 year in the cohort was 9.4% (treated patients, 9.7%; untreated patients, 9.2%). The percent of patients at year 1 with a score of greater than 90 was 87.6%, 87.4% for treated patients and 87.8% for untreated patients. The percent of patients with a Barthel Index score of less than 60 at 5 years in the cohort was 41.4% (treated patients, 41.4%; untreated patients, 41.4%). The percent of patients at year 5 with a score of greater than 90 was 56.3%, 56.1% for treated patients and 56.5% for untreated patients. TICS and Barthel Index scores were significantly associated with each other for patients with Rankin Scores 0-2 (P<0.0001). This was seen at both year 1 and year 5 follow-up, but not for patients with Rankin Score 3-5. At both 1 year and 5 year follow-up, after controlling for Rankin Score, the distribution of Barthel Index scores of untreated patients and treated patients did not significantly differ. At both the 1 year follow-up, baseline Rankin Score, TICS and follow-up Rankin Score were significant predictors of Barthel Score (P<0.0001). At 5 years, only the follow-up Rankin Score was associated with Barthel Score (P<0.0001). Conclusions: Barthel Index Score decreased over time, but does not differ with treatment. The Rankin Score was the main predictor at follow-up of Barthel Index Score distribution.

INTRODUCTION: The decision regarding whether to perform an interventional procedure as a strategy to prevent hemorrhage of an unruptured intracranial aneurysm (UIA) requires careful consideration of procedural risk and the UIA natural history. No randomized trial data are available. The International Study of Unruptured Intracranial Aneurysms (ISUIA) included a prospective cohort, examining hemorrhage risk and treatment risk. Hypothesis: The purpose of this analysis was to compare the factors related to treatment selection and determination of the number of hemorrhages prevented. Methods: Patients were allocated into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort, 471 were in the endovascular cohort and 1917 patients were in the surgical cohort. The cohorts were followed for a median follow-up of 9.2 years. Outcomes were determined prospectively and with central review. The data were grouped together and analyzed to determine treatment decisions. A Cox proportional hazards model predicting hemorrhage developed in the observation cohort and was applied to the surgery and endovascular cohorts across the follow-up period. Results: Significant baseline variable differences between treated and observed patients were aneurysm size, symptoms, age, prior SAH group, geographical region, treatment percentage, aneurysm daughter sacs or multiple lobes, and history of hypertension, smoking and myocardial infarction. Aneurysm site and family history were not significant. Site, size, and aspirin use were significant predictors of hemorrhage. Long-term the predicted hemorrhage rates were 6.7% at 5 years and 8.0% at 10 years in the surgery group and 8.1% and 9.6% for the endovascular group, respectively. For comparison the rates in the observed cohort were 4.1% and 4.8%, respectively. Conclusions: Decisions for treatment are influenced by patient characteristics such as age and medical history, aneurysm characteristics such as size and morphology and center and regional practices. Patients in the treated cohorts were at moderately increased risk for hemorrhage compared to those in the observed cohort.

INTRODUCTION: Cognitive changes can occur following procedural interventions and subarachnoid hemorrhage in unruptured intracranial aneurysms (UIA). The International Study of Unruptured Intracranial Aneurysms conducted cognitive assessment using the Mini-Mental State Exam at baseline and the Telephone Interview Cognitive Status Exam (TICS) at follow-up. Hypothesis: The purpose of this analysis was to compare the 1 year and 5 year outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort and 2388 in the treated cohort. The cohorts were followed annually with measures of neurological status, Rankin Scale and cognition (TICS). Outcomes were determined prospectively. Comparison of outcomes was done using continuous data and by categories. Covariate adjustment was done using general linear models. Stratified analysis was done by Rankin Score at the time of follow-up. Results: The mean TICS score at 1 year in the cohort was 33.4 with a median of 34 (maximum is 40). In the treated patients the mean was 33.5 and in the untreated patients it was 33.3 (P=0.644). However, Rankin Score at 1 year was significant with a higher percentage of 3-5 scores in the treated group (P=0.003) Categorical analysis of the TICS Score when stratified by Rankin Score at 1 year showed small but significant differences, P=0.03 for Rankin 0-2, and P=0.07 for Rankin 3-5. However after adjustment for baseline variables treatment TICS Score was no longer significant.. The 5 year results showed that the untreated patients did worse than the treated group in TICS. However after adjustment no differences were apparent. Conclusions: Cognitive changes associated with treatment may be minor source of disability post-treatment compared to observation and patient outcomes may be worse in the observation group over time. Differences in outcome also were better explained through the Rankin Score at follow-up than by cognitive deficits.

Introduction: There is ongoing debate regarding the rupture risk of an unruptured intracranial aneurysm (UIA), and the predictors of rupture. Hypothesis: There are aneurysm morphology characteristics which predict rupture in patients with an UIA. The purpose of this analysis was to assess for such characteristics utilizing the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort. Methods: Patients were entered prospectively at 61 centers. Patients must have had at least one UIA, which may or may not have been symptomatic. Patients were followed for a median of 9 years and all potential hemorrhages were carefully adjudicated. A case-control design was used. The cases were 57 patients with aneurysmal rupture during followup for whom detailed radiology data were available from arteriography. Controls were 198 size- (+/- 2 mm maximum diameter) and location- (parent artery) matched patients without rupture during followup. Numerous aneurysm morphology characteristics were assessed on arteriogram review. Multivariable condition logistic regression modeling was performed. Results: A total of 57 cases and 198 controls were included. Most (76%) of the 255 cases were women, and 20% had a prior history of SAH from some other aneurysm. There were no differences between cases and controls in aneurysm maximum diameter, aneurysm location, patient age, gender, reason for presentation, or prior medical history. Multivariate analysis identified that only perpendicular height of the aneurysm--the measurement of the aneurysm height at a perpendicular to the center of the aneurysm neck to the aneurysm dome-was an independent predictor of aneurysm rupture. Aspect ratio, size ratio, parent vessel diameter, presence of daughter sac, and aneurysm angle were not independent predictors of rupture. Conclusions: After controlling for aneurysm size and location, the aneurysm perpendicular height remained a predictor of UIA rupture during long-term followup. The assessment of perpendicular height may be helpful in clinical practice, in addition to the other key predictors of UIA rupture, aneurysm maximum diameter and location. Further investigation into the use of perpendicular height as a predictor of rupture in patients with UIA is indicated.

Introduction: Giant intracranial aneurysms are uncommon, have a high risk for rupture and are difficult to treat. The International Study of Unruptured Intracranial Aneurysms (ISUIA) prospective cohort included 187 patients with maximal diameter of 25 mm or greater. This analysis was to determine the long-term prognosis of these aneurysms both treated and untreated. Methods: Patients were enrolled into ISUIA at 61 centers from 1991-1998. A prospective cohort included the managed with observation, surgery or endovascular treatment. Patients were followed for a median of 9.2 years. Aneurysms were measured using a central reading of bi-planar cerebral angiography. Outcomes were determined prospectively and with central review. Results: 187 patients with a maximum diameter of 25 mm were followed. The mean size was 30.3 mm, ranging from 25 to 63 mm. 39% of the aneurysms were surgically treated at baseline, 27% were endovascularly treated, and 32% were managed conservatively;3% had subsequent endovascular treatment and 5% surgical treatment. Patients with giant aneurysms were predominantly women (83%), had a baseline Rankin Score of in 93%, were located predominantly in the anterior circulation (internal carotid 44%, cavernous ICA 28%, middle cerebral 12%). 80% of the patients were symptomatic with cranial nerve deficit in 47% (III and VI nerves), mass effect in 16%, headaches in 44%, orbital pain in 21%, and vision loss in 25%. Smoking history was present in 67%, hypertension in 44%, vascular headaches in 29% and family history in 10%. 70 patients (39%) died during follow-up however 59% were still Rankin 1 or 2. Both surgical and endovascular treated patients had 60-64% good outcome and 34-36% mortality. Untreated patients had a 57% mortality. Subarachnoid hemorrhage occurred in 11 untreated patients and 12 treated patients with most occurring in the first year. Conclusions: Giant intracranial aneurysms are typically symptomatic, and have a high risk of rupture early after diagnosis. Outcome was similar with surgical and endovascular treatment but post-procedure hemorrhage did occur.

Abstract Background: Recent evidence suggests that the presence of small, dense LDL is independently associated with increased risk of developing coronary artery disease. Current methods to subfractionate LDL are time-consuming and/or technically demanding. Therefore, we have sought the development of a less complex LDL subfractionation procedure. Methods: LDL subfractions were separated using the Quantimetrix LipoprintTM LDL System. High-resolution 3% polyacrylamide gel tubes were scanned densitometrically (610 nm) with a Helena EDC system. A computerized method to identify and quantitatively score the resolved LDL subfractions was developed. Results from the Quantimetrix method were compared using 51 plasma samples with values obtained by nondenaturing gradient gel electrophoresis (NDGGE) and nuclear magnetic resonance (NMR) spectroscopy. Results: LDL subfractionation scores correlated significantly (P &lt;0.05) with triglyceride, HDL-cholesterol, apolipoprotein B100, and LDL-cholesterol/apolipoprotein B100 (r = 0.591, −0.392, 0.454, and −0.411, respectively). For 51 samples, the Quantimetrix method classified 21 with small, 14 with intermediate, and 16 with large LDL. Of the 21 samples classified as small by Quantimetrix, 20 (95%) were classified as small (n = 18) or intermediate (n = 2) by NDGGE. All of the 16 specimens classified as large by Quantimetrix were either large (n = 14) or intermediate (n = 2) by NDGGE. LDL score was inversely correlated (r = −0.674; P &lt;0.0001) with LDL particle size determined by NMR spectroscopy. Conclusions: A quantitative method for the assessment of LDL particle size phenotype was developed using the Quantimetrix Lipoprint LDL System. The method can be performed in less than 3 h in batch mode and is suitable for routine use in clinical laboratories.

Abstract While atherosclerosis has been suggested as a risk factor for VTE, previously identified mechanisms for atherosclerosis and VTE differ dramatically. Objectives: To compare (a) VTE-free survival and (b) observed vs. expected number of VTE events, among adult patients with and without aortic atherosclerosis. Design/Setting: Population-based prospective cohort study in Olmsted County, MN. Patients: Age- and sex-stratified random sample of the adult (≥45 years old) Olmsted County population identified over the three-year period, 1993–1995 (n=573), performed as part of the Stroke Prevention: Assessment of Risk in the Community (SPARC) study. Measurements: The SPARC study included a baseline clinical evaluation (interviews, review of medical records), blood pressure measurements, blood sampling, and transesophageal echocardiography (TEE). The Risk Factors for VTE in the Community study identified all incident VTE among Olmsted County residents over the 32-year period, 1966–1997, from which expected VTE events by age and sex were calculated. Results: Over 2830 person-years of follow-up, 12 SPARC patients developed VTE (7 idiopathic). The 4-year VTE-free survival was 99% and 98% for those with and those without any TEE-detected aortic atherosclerosis. Adjusting for age in a Cox proportional hazards model, lack of aortic atherosclerosis was significantly associated with subsequent VTE (p=0.01). Among the 276 patients without atherosclerosis observed for 1423 person-years, 7 VTE were observed compared to 2.6 expected (RR=2.7, 95%CI: 1.1, 5.6). Among the 291 patients with atherosclerosis (plaque ≥2mm), 4 VTE were observed compared to 5.8 expected (RR=0.7, 95%CI: 0.2, 1.8). Conclusions: Atherosclerosis is not a risk factor for incident VTE.