Medical Management Arm Research Articles

Abstract WP142: Investigating the Association of Intracranial Stenosis With Low Wall Shear Stress

Background: Intracranial atherosclerotic disease (ICAD) is associated with high recurrence rates of stroke despite aggressive medical management. Low wall shear stress (WSS) alters endothelial function and changes in WSS within the post-stenotic region of ICAD lesions is a potential driver of stroke recurrence. Methods: Using the SAMMPRIS imaging dataset, we identified medically managed patients with symptomatic middle cerebral artery (MCA) stenosis measured by CTA. WSS was calculated by creating a 3D volumetric mesh from CTA source imaging. Pulsatile flow profile reference standard boundary conditions were applied at pressure outlets to simulate normal hemodynamics. Arterial segments extending from the stenosis to the MCA bifurcation were captured and quantified. Contralateral arterial segments were matched by length and area. The ratio of area with low WSS (<4 dyne/cm 2 ) on both sides was then calculated. Differences in the mean arterial area with low WSS and ratio of area with low WSS were compared using paired Student’s t-test with data presented as mean ± SD. Results: Of 451 cases in SAMMPRIS, the medical management arm had 105 MCA cases of which 47 cases had CTA available and 33 cases were able to be analyzed by computational flow dynamics. Symptomatic ICAD lesions demonstrated significant differences in post stenosis area with low WSS (24.7±43.4 mm 2 vs 2.8±3.4 mm 2 p=0.003) and differences in the low WSS ratio (0.25±0.26 vs0.04±0.05 p<0.001). There was no statistically significant difference in the length and area of the arterial segment post stenosis to the bifurcation and the control length on the contralateral side (11.6±7.4 mm vs 10.6±6.1 mm p=0.566; 80.7±55.0 mm 2 vs 95.4±58.3 mm 2 p=0.298). Conclusion: Area with low WSS after ICAD stenoses is increased in the SAMMPRIS imaging dataset and may be a marker of symptomatic ICAD. Further studies are needed to evaluate the association of post stenotic WSS with symptomatic recurrent stroke.

Abstract 203: Predicting Outcomes After Mechanical Thrombectomy: Early vs Delayed Neurological Improvement in the SELECT Database

Introduction Understanding of patient benefit and improvement following mechanical thrombectomy in ischemic stroke has made tremendous strides in recent years, however clinicians still struggle to accurately predict patient outcomes and long‐term neurological functioning following large vessel occlusion and endovascular therapy. These limitations are further complicated by a highly variable time course of improvement following intervention that spans from minutes to months. Prior literature has shown that successful reperfusion is associated with better outcomes even in the absence of early improvement. Delayed neurological improvement may be the result of microvasculature effects and inflammatory changes, and is likely multifactorial. Improved understanding of predictors of early versus delayed neurological improvement in this population may help inform goals of care, aid in clinical decision making, and manage patient and family expectations. Methods Patient data from the SELECT database was retrospectively analyzed. The SELECT study was a prospective, non‐randomized, multicenter cohort study that enrolled patients with acute ischemic stroke due to anterior circulation large vessel occlusion at nine US centers between 1/2016 and 2/2018, with patients falling into either the mechanical thrombectomy or medical management arm. Only patients in the mechanical thrombectomy arm (n=149) were included in this analysis. Possible predictors of early vs late neurological improvement were segregated into pre‐procedure (age, NIHSS at baseline, IV thrombolytic therapy, transfer status, occlusion location, ischemic core, ischemic penumbra, hypoperfusion intensity ratio, successful reperfusion, type of anesthesia, time from last known well to puncture, time from puncture to reperfusion) and post‐procedure (NIHSS at 24‐hour follow‐up, ASPECTS on follow‐up imaging, ASPECTS point loss from baseline, infarct volume on follow‐up imaging, infarct growth from baseline ischemic core, neurological worsening, midline shift, hemorrhagic transformation and type). Backwards stepwise regression was used to identify significant predictors of early and delayed improvement. Results Pre‐procedure predictors of early neurological improvement (defined as mRS 0‐2 at discharge) were age (p=0.001), NIHSS score (p=0.002), ischemic core volume (p=0.001), transfer status (p=0.019), and successful reperfusion (defined as mTICI 2b or better, p=0.001). Post‐procedure predictor of early neurological improvement was NIHSS score at 24 hours (p<0.001). Pre‐procedure predictor of delayed neurological improvement (defined as mRS 0‐2 at 90 days among those who did not achieve early neurological improvement) was ischemic core volume (p=0.003). Post‐procedure predictors of delayed neurological improvement were final infarct volume (p=0.012), change in ASPECTS on follow‐up imaging (p=0.001), and growth in infarct size (p=0.030). Pre‐procedure predictors of early excellent outcome (defined as mRS 0‐1 at discharge) were age (p=0.001), NIHSS score (p<0.001), successful reperfusion (p=0.001), ischemic core volume (p=0.004), and infarct growth rate (p=0.034). Pre‐procedure predictor of delayed excellent outcome (defined as mRS 0‐1 at 90 days among those who did not achieve early excellent outcome) was NIHSS score (p=0.002). Additionally, midline shift of 5mm or more at 24 hours was associated with poor outcome at 90 days. Conclusion Several demographic, imaging, and clinical factors were found to correlate with either early or delayed neurological improvement. Further investigation may help delineate how these predictors can be utilized to inform clinical decisions and discussions regarding stroke patients receiving mechanical thrombectomy.

Outcome of 107 conservatively managed unruptured brain arteriovenous malformations: a single center's 30-year experience.

Since the publication of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the management of unruptured brain arteriovenous malformations (bAVMs) has been controversially discussed. Long-term follow-up data on the exclusively conservative management of unruptured bAVMs are scarce. The authors evaluated the long-term outcomes of patients with unruptured untreated bAVMs in a real-life cohort. A retrospective observational cohort of 107 patients (of 897 bAVM patients referred to the authors' institution) with a diagnosis of unruptured and conservatively managed bAVMs is presented. AVMs of all Spetzler-Martin grades were observed. The mean follow-up period was 84 months. In 44% of patients, a follow-up period of 5 years or longer was observed. A national death register comparison completed the outcome analysis. The median age at diagnosis, sex distribution, neurological presentation, and modified Rankin Scale score were comparable to the patients in the medical management arm of the ARUBA study. Patients were mainly young, predominantly male, and in good clinical condition. Similar to the ARUBA cohort, 77% of this study's cohort presented in an excellent clinical status at the time of last follow-up. However, 17% of patients had at least one hemorrhage, resulting in an overall annual hemorrhage risk of 2.7% in the observation period. Moreover, the cumulative 1-, 5-, and 10-year overall hemorrhage rates were 3.0%, 11.3%, and 15.3%, respectively. Consequently, the long-term follow-up AVM-related mortality rate amounted to 8%. The estimated median overall survival after AVM diagnosis was 19.3 years (95% CI 14.0-24.6 years). A multivariate Cox regression model revealed temporal and deep-seated localization as an independent risk factor for AVM hemorrhage, while the presence of seizures reached borderline significance as a risk factor. The authors' results represent the long-term course of unruptured untreated bAVMs. Their data support the conclusion that even in the post-ARUBA era, tailored active treatment options may be offered to patients with unruptured bAVMs. For patient counseling, individual risk factors should be weighed against the center's treatment-specific risks.

Effect of endovascular therapy in large anterior circulation ischaemic strokes: A systematic review and meta-analysis of randomised controlled trials.

The benefit of endovascular treatment in large anterior circulation ischaemic strokes with low ASPECTS score (<6) is uncertain. Recent randomised studies have demonstrated the benefit of endovascular treatment (EVT) in large ischaemic strokes. The present meta-analysis aims to assess the combined effect of these studies on efficacy and safety of endovascular treatment in this group of patients. We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases MEDLINE, PubMed, EMBASE, SCOPUS, Google Scholar, Tripdatabase were searched for randomised controlled trials with at least 50 participants from inception until February 16, 2023. The primary efficacy outcome analysed was the relative risk of functional independence defined as mRS - 0-2 at 90 days. Secondary efficacy outcomes included early neurological improvement, death due to any cause at 90 days and proportion of patients requiring decompressive hemicraniectomy. The primary safety outcome was the risk of developing symptomatic intracerebral haemorrhage (sICH). A total of three studies (RESCUE Japan-LIMIT, SELECT 2 and ANGEL ASPECTS) involving 1011 patients; 510 in the EVT arm and 501 in the medical management (MM) arm met the defined criteria (ASPECTS-3-5). The combined RR for the primary outcome of mRS 0-2 was 2.53 [1.84-3.47] (p = <0.0001) favouring EVT over MM. The primary safety outcome of sICH was not significant in the EVT arm with a combined RR of 1.84 [0.94-3.60] (p = 0.5157). Mortality rates were similar in both arms (26.67% in EVT arm vs 27.94% in MM arm) with a combined RR of 0.95 [0.78; 1.16] (p = 1.000). In patients with Large vessel occlusion (LVO) and low ASPECTS (3-5), EVT was associated with higher likelihood of achieving functional independence and early neurologic improvement but did not provide any mortality benefit.

Mechanical thrombectomy in low Alberta Stroke Program Early Computed Tomographic Score: A systematic review and meta-analysis of randomized controlled trials.

Due to their poor natural history and lack in level-I evidence, patients with large vessel occlusion and large core infarcts (Alberta Stroke Program Early Computed Tomographic Score <6) have been excluded from receiving mechanical thrombectomy. This systematic review and meta-analysis seeks to summarize current evidence from published randomized controlled trials to compare the safety and efficacy of mechanical thrombectomy with optimal medical therapy in treating stroke patients with large core infarcts. We searched PubMed and EMBASE for randomized controlled trials investigating the safety and efficacy of mechanical thrombectomy vs optimal medical therapy in patients presenting with large vessel occlusion and large infarcts. Basic demographic and comorbidities were assessed, and clinical outcomes were compared, including modified Rankin scale 0-3, and 0-2 at 3 months, symptomatic intracranial hemorrhage, decompressive hemicortectomy, and 90-day mortality. Three randomized controlled trials totaling 1011 patients (501 and 510 in the medical management and mechanical thrombectomy arm, respectively) were included. Patients undergoing mechanical thrombectomy had significantly higher odds of achieving better functional outcomes at 3 months: Modified Rankin scale 0-2 (OR = 3.05, 95% CI = 2.101-4.4021, p < 0.0001) and modified Rankin scale 0-3 (OR = 2.20, 95% CI = 1.67-2.89, p < 0.0001) as compared to those receiving optimal medical management. There were no differences between groups in 90-day mortality (OR = 0.93, 95% CI = 0.70-1.23, p = 0.60), symptomatic intracranial hemorrhage (OR = 1.89, 95% = CI 0.95-3.77, p = 0.07) or decompressive hemicraniectomy (OR = 1.25, 95% CI = 0.69-2.25, p = 0.46). Mechanical thrombectomy for patients with large infarcts is associated with improved functional outcomes and a similar safety profile compared to optimal medical management. Ongoing trials will help better refine the target population that benefits the most from treatment.

Neurointerventional Advances in 2022

Neurointerventional Advances in 2022

Abstract TMP73: Patterns Of Index And Recurrent Stroke In Patients With Intracranial Stenosis

Background and Purpose: Pattern of infarct due to ICAS (e.g. borderzone) may predict recurrent stroke risk. We sought to describe the patterns of index and recurrent infarcts in patients enrolled in the medical arm of the SAMMPRIS Trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis). Methods: - Patients enrolled in the medical management arm of the SAMMPRIS trial with infarct as the qualifying event who had CT or MRI, or those with a recurrent infarct in the territory of the symptomatic artery during follow up were included. Infarct pattern for both the index infarct and any recurrent infarct in the territory was determined using criteria defined in prior SAMMPRIS publications as borderzone, MCA artery core, and perforator for anterior circulation and cerebellar, perforator and distal for posterior circulation (see figure for examples). Infarct pattern was adjudicated independently by 2 reviewers, with a 3 rd reviewer as tiebreaker. Results: - Among the 142 patients who had index infarcts in the anterior circulation (n=101) and posterior (n=41) circulation, the patterns were: 53 (37.3%) borderzone, 24 (16.9%) MCA core, 35 (24.6%) perforator, 13 (9.2%) distal, and 17 (12%) cerebellar. Among the 31 who had recurrent infarct in the territory, the patterns were: 10 (32.3%) borderzone, 6 (19.4%) MCA core, 6 (19.4%) perforator, 4 (12.9%) distal, 1 (3.2%) cerebellar, and 4 (12.9%) were missing imaging. Of the recurrent infarcts in territory, 21 had both index infarct and recurrent infarct in territory adjudications, with 11 demonstrating the same pattern of infarct for both events (7 borderzone, 2 core, 2 perforator). Conclusions: - The majority of patients with stroke due to severe symptomatic intracranial stenosis demonstrated borderzone pattern of infarct for index and recurrent infarcts. Ongoing analyses of this dataset will determine the association between pattern of index stroke and risk of recurrent stroke.

Primary trabeculectomy versus primary glaucoma eye drops for newly diagnosed advanced glaucoma: TAGS RCT.

Patients diagnosed with advanced primary open-angle glaucoma are at a high risk of lifetime blindness. Uncertainty exists about whether primary medical management (glaucoma eye drops) or primary surgical treatment (augmented trabeculectomy) provide the best and safest patient outcomes. To compare primary medical management with primary surgical treatment (augmented trabeculectomy) in patients with primary open-angle glaucoma presenting with advanced disease in terms of health-related quality of life, clinical effectiveness, safety and cost-effectiveness. This was a two-arm, parallel, multicentre, pragmatic randomised controlled trial. Secondary care eye services. Adult patients presenting with advanced primary open-angle glaucoma in at least one eye, as defined by the Hodapp-Parrish-Anderson classification of severe glaucoma. Primary medical treatment - escalating medical management with glaucoma eye drops. Primary trabeculectomy treatment - trabeculectomy augmented with mitomycin C. The primary outcome was health-related quality of life measured with the Visual Function Questionnaire-25 at 2 years post randomisation. Secondary outcomes were mean intraocular pressure; EQ-5D-5L; Health Utilities Index 3; Glaucoma Utility Index; cost and cost-effectiveness; generic, vision-specific and disease-specific health-related quality of life; clinical effectiveness; and safety. A total of 453 participants were recruited. The mean age of the participants was 67 years (standard deviation 12 years) in the trabeculectomy arm and 68 years (standard deviation 12 years) in the medical management arm. Over 65% of participants were male and more than 80% were white. At 24 months, the mean difference in Visual Function Questionnaire-25 score was 1.06 (95% confidence interval -1.32 to 3.43; p = 0.383). There was no evidence of a difference between arms in the EQ-5D-5L score, the Health Utilities Index or the Glaucoma Utility Index. At 24 months, the mean intraocular pressure was 12.40 mmHg in the trabeculectomy arm and 15.07 mmHg in the medical management arm (mean difference -2.75 mmHg, 95% confidence interval -3.84 to -1.66 mmHg; p < 0.001). Fewer types of glaucoma eye drops were required in the trabeculectomy arm. LogMAR visual acuity was slightly better in the medical management arm (mean difference 0.07, 95% confidence interval 0.02 to 0.11; p = 0.006) than in the trabeculectomy arm. There was no evidence of difference in safety between the two arms. A discrete choice experiment updated the utility values for the Glaucoma Utility Index. The within-trial economic analysis found a small increase in the mean EQ-5D-5L score (0.04) and that trabeculectomy has a higher probability of being cost-effective than medical management. The incremental cost of trabeculectomy per quality-adjusted life-year was £45,456. Therefore, at 2 years, surgery is unlikely to be considered cost-effective at a threshold of £20,000 per quality-adjusted life-year. When extrapolated over a patient's lifetime in a model-based analysis, trabeculectomy, compared with medical treatment, was associated with higher costs (average £2687), a larger number of quality-adjusted life-years (average 0.28) and higher incremental cost per quality-adjusted life-year gained (average £9679). The likelihood of trabeculectomy being cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life year gained was 73%. Our results suggested that there was no difference between treatment arms in health-related quality of life, as measured with the Visual Function Questionnaire-25 at 24 months. Intraocular pressure was better controlled in the trabeculectomy arm, and this may reduce visual field progression. Modelling over the patient's lifetime suggests that trabeculectomy may be cost-effective over the range of values of society's willingness to pay for a quality-adjusted life-year. Further follow-up of participants will allow us to estimate the long-term differences of disease progression, patient experience and cost-effectiveness. Current Controlled Trials ISRCTN56878850. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 72. See the NIHR Journals Library website for further project information.

Primary trabeculectomy for advanced glaucoma: pragmatic multicentre randomised controlled trial (TAGS)

ObjectiveTo determine whether primary trabeculectomy or primary medical treatment produces better outcomes in term of quality of life, clinical effectiveness, and safety in patients presenting with advanced glaucoma.DesignPragmatic multicentre randomised...

Cost-Effectiveness of Thoracotomy Approach for the Implantation of a Centrifugal Left Ventricular Assist Device.

This study reports the first analysis regarding cost-effectiveness of left ventricular assist device (LVAD) implantation via thoracotomy. Cost-effectiveness of LVADs implanted via the traditional surgical approach of sternotomy has been improved through the years because of technological advances, along with understanding the importance of patient selection and postimplant management have on positively affecting outcomes. Given the positive clinical outcomes of the thoracotomy approach, we seek to study the cost-effectiveness of a centrifugal LVAD via this less invasive approach. We developed a Markov model. Survival and quality of life inputs (QALY) for the LVAD arm were based on data from the LATERAL clinical trial. For the Medical Management arm, survival was derived from the Seattle Heart Failure Model. The heart transplant probability was derived from INTERMACS. Survival after heart transplantation used International Society for Heart and Lung Transplantation data. Cost inputs were calculated based on Medicare data and past literature. The incremental cost-effectiveness ratio was found to be $64,632 per quality adjusted life year and $57,891 per life year in the bridge to transplant indication. These results demonstrate further improvement in the overall cost-effectiveness of LVAD therapy and confirm implantation of LVADs via a less invasive approach as being cost-effective.

Cost-Effectiveness of a Small Intrapericardial Centrifugal LVAD versus Medical Management in Destination Therapy Patients in the UK

Continuous-flow Left Ventricular Assist Devices (LVADs) as destination therapy (DT) are a recommended treatment by NICE England for end stage heart failure patients ineligible for heart transplantation. While DT is frequently used as an LVAD indication across other major European countries and in the US with consistent improvements in quality-of-life and longevity, NHS England does not fund DT mainly due to cost-effectiveness concerns. Based on the recently published ENDURANCE Supplemental trial studying DT patients, we assessed for the first time the cost-effectiveness of LVADs in the DT indication compared to medical management in the NHS England. We built a Markov multiple-state economic model using NHS cost data. Clinical inputs were based on LVAD trial data. Survival and adverse event rates were taken from the contemporary ENDURANCE Supplemental trial for the LVAD arm. Survival for the medical management arm was based on the Seattle Heart Failure Model estimates in the absence of contemporary clinical trials for this population. Incremental cost-effectiveness ratios (ICERs) were calculated over a life time horizon. We conducted various sensitivity analyses. A discount rate of 3 % per year was applied to costs and benefits. The ICER of the small intrapericardial centrifugal LVAD per quality-adjusted life year (QALY) gained was £45,618 and £34,375 per life-year gained (LY). Costs and utilities were £209,241 and 3.42 QALYs for the LVAD arm versus £78,196 and 0.54 QALYs for the medical management arm. Sensitivity analyses showed robust results. The implantation of a small intrapericardial centrifugal LVAD in patients with the DT indication who are not eligible for heart transplantation is a cost-effective therapy in the NHS England healthcare system under the willingness-to-pay threshold of £50,000 per QALY, which applies for end-of life care.

Cost-Effectiveness of Thoracotomy Approach for the Implantation of a Small Intrapericardial Centrifugal LVAD

This is the first assessment of cost-effectiveness of Left Ventricular Assist Device (LVAD) implantation via thoracotomy. Cost effectiveness of LVADs implanted through the traditional surgical approach of sternotomy has been improved through the years due to technological advances, along with understanding the importance patient selection and post-implant management have on positively affecting outcomes. Given the positive clinical outcomes of the thoracotomy approach we seek to study the cost-effectiveness of a small intrapericardial centrifugal LVAD via this less invasive approach. We developed a Markov model to assess the cost-effectiveness of LVAD implantation via thoracotomy. Survival and quality of life inputs for the LVAD arm were based on data from the LATERAL clinical trial. For the Medical Management arm, survival was derived from the Seattle Heart Failure Model. Transplant probability was derived from INTERMACS. Survival after heart transplantation used published UNOS data. Cost inputs were calculated based on Medicare data and past literature. Sensitivity Analyses were conducted. The incremental cost-effectiveness ratio (ICER) of a small intrapericardial centrifugal LVAD implantation via thoracotomy was found to be $63,983 per quality adjusted life years (QALY) and $53,387 per life years gained in the bridge to transplant indication. Given the new UNOS heart allocation system, we also examined scenarios of lower transplant rates. In both scenarios the ICER improved and was significantly below the traditional US willingness-to-pay threshold of $50,000/QALY. At 10% transplant rate the ICER was $39,839/QALY and at 5%, $34,468/QALY. We believe this improvement in the ICER is driven by the excellent survival in the LATERAL study. These results demonstrate further improvement in the cost-effectiveness of LVADs and confirm implantation of LVADs via a less invasive approach as being cost-effective. In a Markov model assessing the cost-effectiveness of Thoracotomy Approach for the Implantation of LVADs, we found an ICER of $64,684/QALY. In cases of low heart transplant rates the ICER was below $50,000/QALY. These outcomes demonstrate a significant improvement in the ICER and confirm that implantation via thoracotomy of a small intrapericardial centrifugal LVAD in certain scenarios is cost-effective.

Multimodal cerebral arteriovenous malformation treatment: a 12-year experience and comparison of key outcomes to ARUBA.

Curative treatment of unruptured brain arteriovenous malformations (AVMs) remains controversial after the only randomized controlled trial, A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), was halted prematurely because interim analysis revealed superiority of the medical management group. In contrast, meta-analyses of retrospective cohorts suggest that intervention is much safer than was found in ARUBA. The authors retrospectively analyzed 318 consecutive adult patients with brain AVMs treated at their institution with embolization, surgery, and/or proton beam radiosurgery. Analysis was performed in 142 ARUBA-eligible patients (baseline modified Rankin Scale [mRS] score 0-1, no history of hemorrhage), and results were compared to primary and secondary outcomes from ARUBA, as well as to natural history cohorts. The annualized stroke rate (hemorrhagic or ischemic) in this cohort was 1.8%, 4.9% in the first 12 months and 0.8% after the first 12 months, which was lower than in natural history studies and the ARUBA medical management arm (p = 0.001). The primary ARUBA endpoint of symptomatic stroke was reached in 13 patients (9.2%), which compares favorably to the ARUBA intervention arm (39.6%, p = 0.0001) and is similar to the ARUBA medical management arm (9.2%, p = 1.0). The secondary ARUBA endpoint (mRS score ≥ 2 at 5 years of follow-up) was reached in 14.3% of patients, compared to 40.5% in the ARUBA intervention arm (p = 0.002) and 16.7% in the ARUBA medical management arm (p = 0.6). This multimodal approach to the selection and treatment of patients with brain AVMs yields good clinical outcomes with key safety endpoints (stroke, death, and mRS score 0-1) better than the ARUBA intervention arm and similar to the ARUBA medical arm at 5 years of follow-up. Results compare favorably to natural history cohorts at longer follow-up times. This suggests that tertiary care centers with integrated programs, expertise in patient selection, and individualized treatment approaches may allow for better clinical outcomes than reported in ARUBA. It supports current registry studies and merits consideration of future randomized controlled trials in patients with brain AVMs.

Management of secretory otitis media: a prospective randomised study comparing medical management with early surgical intervention

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Secretory otitis media is the most common cause of conductive hearing loss in children. Though self-limiting recurrent disease can cause speech and language delay, cognitive impairment and behavioural problems in the long term. This is a prospective study of the epidemiological profile, predisposing factors, clinical profile of secretory otitis media. This study also compares the conservative treatment with early surgical Treatment in Patient with secretory otitis media.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; The study is a prospective randomised study of patients presenting with conductive hearing loss diagnosed by pure tone audiometry. The patients were randomized into two groups of 25 patients each. The medical management arm received antihistamines and decongestants and the surgical arm patient underwent myringotomy with grommet insertion. Patients with adenoid hypertrophy underwent adenoidectomy as an additional procedure. The patients were followed up regularly and where evaluated at the end of 12 months for symptomatic improvement and hearing improvement by Pure Tone Audiogram and impedance audiogram. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The most common age group affected was between 5-15 yrs with hard of hearing and aural fullness being the most common presenting complaint. Eustachian tube dysfunction with adenoid hypertrophy was the most common precipitating factor (68%) followed by allergy and gastro esophageal reflux disease. Compared to medical treatment which resulted in a successful treatment outcome in 40% of patients, cases which underwent surgical treatment had successful outcome in 70% of cases.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Surgical management in the form of adenoidectomy/myringotomy with grommet insertion has better long term outcome in terms of hearing impairment and disease relapse and recurrence.&lt;/p&gt;

Cost-Effectiveness of a Small Intrapericardial Centrifugal LVAD versus Medical Management and Heart Transplantation

Purpose There is limited data on the cost-effectiveness of continuous-flow Left Ventricular Assist Devices (LVADs) in the U.S. and especially for the bridge to transplant indication. We studied for the first time the cost-effectiveness of a small intrapericardial centrifugal LVAD in its primary indications compared to medical management and subsequent heart transplantation using the respective clinical trial data. Methods We developed a Markov economic framework to assess the cost-effectiveness of a small intrapericardial centrifugal LVAD. Survival and quality of life (QoL) inputs for the LVAD arm were based on individual patient data (IPD) from the ADVANCE-BTT + CAP, ENDURANCE and ENDURANCE Supplemental clinical trials. To better assess survival in the medical management arm, and in the absence of contemporary trials randomizing patients to LVAD and medical management, estimates from the Seattle Heart Failure Model (SHFM) had to be used. Costs inputs were calculated based on Medicare cost data (Instant Health Data, IHD) and, when appropriate prior published literature. Time horizon was lifetime. One-way, Scenario and Probabilistic Sensitivity Analyses were conducted. Costs and benefits were appropriately discounted at 3% per year. Results The incremental cost-effectiveness ratio (ICER) of the small intrapericardial centrifugal LVAD was calculated $76,240 per quality-adjusted life years (QALY) and $64,415 per life-years gained (LY) for the bridge to transplant (BTT) indication. Costs and utilities were $384,829 and 7.08 QALYs for the LVAD arm vs. $104,645 and 3.41 QALYs for the medical management arm. These results suggest substantial improvement, to the ICER of LVADs in the BTT indication, driven by long-term data, technological advancements and payment variations. This re-opens the discussion of LVADs’ cost-effectiveness. Conclusion In this analysis assessing the cost-effectiveness a small intrapericardial centrifugal LVAD, we found an ICER of $76,240 per QALY for the BTT indication. These outcomes signify a substantial improvement and re-open the discussion around LVAD's cost-effectiveness.

Accuracy of Seattle Heart Failure Model and HeartMate II Risk Score in Non-Inotrope-Dependent Advanced Heart Failure Patients: Insights From the ROADMAP Study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients).

Timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients not on inotropes is unclear. Relevant prediction models exist (SHFM [Seattle Heart Failure Model] and HMRS [HeartMate II Risk Score]), but use in this group is not established. ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) is a prospective, multicenter, nonrandomized study of 200 advanced heart failure patients not on inotropes who met indications for LVAD implantation, comparing the effectiveness of HeartMate II support versus optimal medical management. We compared SHFM-predicted versus observed survival (overall survival and LVAD-free survival) in the optimal medical management arm (n=103) and HMRS-predicted versus observed survival in all LVAD patients (n=111) using Cox modeling, receiver-operator characteristic (ROC) curves, and calibration plots. In the optimal medical management cohort, the SHFM was a significant predictor of survival (hazard ratio=2.98; P<0.001; ROC area under the curve=0.71; P<0.001) but not LVAD-free survival (hazard ratio=1.41; P=0.097; ROC area under the curve=0.56; P=0.314). SHFM showed adequate calibration for survival but overestimated LVAD-free survival. In the LVAD cohort, the HMRS had marginal discrimination at 3 (Cox P=0.23; ROC area under the curve=0.71; P=0.026) and 12 months (Cox P=0.036; ROC area under the curve=0.62; P=0.122), but calibration was poor, underestimating survival across time and risk subgroups. In non-inotrope-dependent advanced heart failure patients receiving optimal medical management, the SHFM was predictive of overall survival but underestimated the risk of clinical worsening and LVAD implantation. Among LVAD patients, the HMRS had marginal discrimination and underestimated survival post-LVAD implantation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01452802.

Thoracoscopic Ablation With Appendage Ligation Versus Medical Therapy for Stroke Prevention: A Proof-of-Concept Randomized Trial.

Atrial fibrillation (AF) has a demonstrable effect on quality of life (QOL). Recurrent stroke occurs in 10% of patients with AF. The objective of this study was to demonstrate proof of concept that thoracoscopic pulmonary vein isolation and atrial appendage ligation (TPVIAL) could prevent recurrent stroke and could potentially improve QOL in patients with AF with a previous stroke. The study was a National Institutes of Health-funded single-center proof-of-concept design that randomized 23 patients with AF-related stroke to TPVIAL (n = 12) or to medical management (n = 11). Quality of life was the primary outcome variable; secondary end points included restoration of rhythm, recurrent stroke, and surgical morbidity. Quality-of-life subscores at 3 and 6 months revealed improvements in energy and decreases in fatigue in the TPVIAL arm [baseline, 33 (19.8); 3 months, 49.5 (20.6), P = 0.01; 6 months, 55.5 (14.4), P = 0.03]. At 12-month follow-up, there were no recurrent strokes in the TPVIAL group. In the medically treated arm, two patients at 6 months (P = 0.22) and three total patients at 12 months (P = 0.09) had recurrent ischemic stroke. There was one death in the medical management arm. In the TPVIAL arm, no AF recurrence occurred in patients with paroxysmal AF, and one patient had recurrence of persistent and long-standing AF. Seven patients in the TPVIAL arm discontinued warfarin therapy for secondary stroke prevention. This small proof-of-concept study showed that TPVIAL improved QOL on two subscores and restored normal sinus rhythm in all but one patient, and it showed the potential to prevent secondary stroke. A larger study will be needed.

The Technique of Endovascular Intracranial Revascularization

Intracranial atherosclerosis was traditionally believed to carry a risk of stroke of 8% to 22% per annum. The annualized stroke rate in the recent stenting and aggressive medical management for preventing stroke in intracranial stenosis (SAMMPRIS) trial medical management arm was 12.2%. This trial was halted due to excessive periprocedural events in the stent arm. This stroke rate is still unacceptably, high and a treatment strategy is still needed. SAMMPRIS has no bearing on angioplasty alone. Angioplasty alone has always been our primary intervention for intracranial atherosclerosis and remains so to this day due to its relative simplicity, low complication rate, and efficacy. We have, however, made adjustments to our patient management regimen based on the results of SAMMPRIS. This paper outlines our current patient selection, procedural technique, and post-procedure management. The complications we have encountered while developing our technique are described along with how to avoid them and how to manage them. Our most recent results (since previous publications) are also discussed.

Commentary

Commentary

Reviving Intracranial Angioplasty and Stenting "SAMMPRIS and beyond".

We review the methods and results of Stenting and Aggressive Medical Management for Preventing Recurrent Stroke (SAMMPRIS) and provide a critical review of its strengths and limitations. In SAMMPRIS, the aggressive medical treatment arm (AMT arm) did substantially better than the Wingspan Stenting plus aggressive medical management arm (WS+ arm). Complications in the first 30 days post intervention led to the disparity between treatment arms. A major contribution of SAMMPRIS was the added value that AMT and lifestyle change may provide, when compared to a precursor trial, Warfarin–Aspirin Symptomatic Intracranial Disease (WASID), designed to prevent stroke in persons with high-grade symptomatic intracranial occlusive disease, however, the results of neither of these two trials have ever been reproduced. On the other hand, we argue that technical limitations of the Wingspan stent system (WS System) and lack of an angioplasty only intervention arm may have led to a premature launch of the trial and early termination of the study. Future randomized trials with different devices and modified patient selection criteria are warranted.