Objective Since the introduction of the cut-and-sew Cox maze procedure for atrial fibrillation, there has been substantial innovation in techniques for ablation. Use of alternative energy sources for ...ablation simplified the procedure and has resulted in dramatic increase in the number of patients with atrial fibrillation treated by surgical ablation. Despite its increasingly widespread adoption, there is lack of rigorous clinical evidence to establish this procedure as an effective clinical therapy. Methods This article describes a comparative effectiveness randomized trial, supported by the Cardiothoracic Surgical Clinical Trials Network, of surgical ablation with left atrial appendage closure versus left atrial appendage closure alone in patients with persistent and long-standing persistent atrial fibrillation undergoing mitral valve surgery. Nested within this trial is a further randomized comparison of 2 different lesions sets: pulmonary vein isolation and the full maze lesion set. Results This article addresses trial design challenges, including how best to characterize the target population, operationalize freedom from atrial fibrillation as a primary end point, account for the impact of antiarrhythmic drugs, and measure and analyze secondary end points, such as postoperative atrial fibrillation load. Conclusions This article concludes by discussing how insights that emerge from this trial may affect surgical practice and guide future research in this area.
Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction. ...Prior research in experimental and human heart failure has shown that CCM signals normalize phosphorylation of key proteins and expression of genes coding for proteins involved in regulation of calcium cycling and contraction. The results of prior clinical studies of CCM have supported its safety and efficacy. A large-scale clinical study, the FIX-HF-5 study, is currently underway to test the safety and efficacy of this treatment. In this article, we provide an overview of the system used to deliver CCM signals, the implant procedure, and the details and rationale of the FIX-HF-5 study design. Baseline characteristics for patients randomized in this trial are also presented.
OBJECTIVE The 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification of pulmonary adenocarcinomas ...introduces adenocarcinoma in situ and minimally invasive carcinoma and categorizes adenocarcinoma with more extensive invasion by the predominant subtype. Data have shown that wedge or segmentectomy (W/S) may be appropriate for in situ and minimally invasive adenocarcinoma, but whether sublobar resection is appropriate for tumors with more extensive invasion is unclear. The aim of this pilot study is to evaluate whether there are any trends regarding the impact of invasion and subtypes of carcinoma regarding survival in lobectomy vs W/S procedures using a comprehensive histologic evaluation. METHODS Eighty-five surgical specimens (59 lobectomies, 26 W/Ss) were reviewed. Histologic type, size, pleural, lymphovascular invasion, and necrosis were recorded. Adenocarcinomas were classified by 2011 IASLC/ATS/ERS guidelines with each histologic pattern recorded as a percentage of the total tumor. Statistical analysis was performed using SAS, version 9.2. Proportional hazards regression analysis was used to evaluate survival according to resection type (lobectomy or W/S) adjusting for tumor size and the predominant histology. RESULTS Multivariate analysis did not show a statistically significant difference in survival between lobectomy and W/S specimens adjusting for tumor size, regardless of histologic subtype or other negative predictors of prognosis ( P = .7704). CONCLUSIONS Our findings corroborate the prognostic significance of the 2011 adenocarcinoma subtyping classification and additionally suggest that lobectomy does not offer an overall survival advantage over W/S regardless of histologic subtype. Therefore, this finding suggests that limited resection may be appropriate for small size tumors, particularly those ≤ 2 cm with invasive histology.
Objective Patients with coronary artery disease complicated by moderate ischemic mitral regurgitation have demonstrably poorer outcome than do patients with coronary artery disease but without mitral ...regurgitation. The optimal treatment of this condition has become increasingly controversial, and a randomized trial evaluating current practices is warranted. Methods We describe the design and initial execution of the Cardiothoracic Surgical Trials Network Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial. Results This is an ongoing prospective, multicenter, randomized, controlled clinical trial designed to test the safety and efficacy of mitral repair in addition to coronary artery bypass grafting in the treatment of moderate ischemic mitral regurgitation. Conclusions The results of the Cardiothoracic Surgical Trials Network Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial will provide long-awaited information on controversial therapies for this morbid disease process.
Kidney allocation system allows blood type B candidates accept kidneys from A2/A2B donors. There is no mandate by UNOS on which the anti-A2 level is acceptable. We aimed to investigate the safety of ...kidney transplant in blood group B patients with anti-A2 titers ≤16.
We performed 41 A2-incompatible kidney transplants in blood group B recipients between May 2015 and September 2019. Clinical outcomes were compared with a control group of 75 blood group B recipients who received blood group compatible kidney transplantation at the same period.
Of the 41 recipients, 85% were male, 48% African American, with a median age of 53 (20-73) y. Thirty-eight (93%) were deceased-donor and 3 (7%) were living-donor kidney transplant recipients. Pretransplant anti-A2 IgG titers were 2 in 16, 4 in 9, 8 in 6, and 16 in 5 and too weak to titer in 5 recipients. Eight patients had pretransplant donor-specific antibodies. During a median follow-up of 32.6 mo (6-57.3) patient and graft survival were 100% and 92% in the A2-incompatible kidney transplant group, and 91% and 92% in the blood group compatible group, respectively. Twelve A2-incompatible recipients underwent a 21 clinically indicated kidney biopsies at a median 28 d (6-390) after transplantation. None of the patients developed acute antibody-mediated rejection and 2 patients (5%) had acute T-cell-mediated rejection. Interestingly, peritubular capillary C4d positivity was seen in 7 biopsies which did not have any findings of acute rejection or microvascular inflammation but not in any of the rejection-free biopsies in the control group. C4d positivity was persistent in 5 of those patients who had follow-up biopsies.
A2-incompatible transplantation is safe in patients with anti-A2 titers ≤16 with excellent short-term kidney allograft outcomes. C4d positivity is frequent in allograft biopsies without acute rejection.
Abstract Background Although many studies of heart failure therapies test improvements of patient condition in terms of mean changes of quality of life (QoL) or exercise tolerance (ET) measures, it ...is of increasing interest to quantify the proportion of patients that “respond” to therapy and understand factors predicting response. These questions can be address through the use of a “responder analysis,” in which the proportion of patients in whom a measure of QoL or ET improves by a minimum amount is determined. Here, we review the principles of a “responder analysis.” Methods and Results We used data from published studies of cardiac resynchronization therapy to model the results of a responder analysis and original data from a recent study of cardiac contractility modulation to illustrate the many facets of such an analysis that need to be understood and investigated further. Some of these areas include: understanding how to choose criteria for response; how to deal with differing results obtained with different measures of response; and how to deal with potentially conflicting information provided by a responder analysis and the more standard comparison of mean changes. Conclusions Additional prospective studies will help advance understanding the optimal way to use responder analyses in heart failure trials.
Summary Background The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations ...(ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design block size 2, 4, or 6, stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00389181. Findings Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months SD 19·7), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14–0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management. Interpretation The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.
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