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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] cm2 vs 1.8 [0.6] cm2; 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.

Objectives The aim of this study was to report the 2-year results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial and confirm the interim Bayesian analysis. Background Transcatheter aortic valve replacement (TAVR) with a self-expanding valve was noninferior to surgery in patients with severe aortic stenosis and intermediate operative risk using Bayesian statistical methods. Novel Bayesian designs have been used to shorten the time to primary endpoint analysis in randomized clinical trials, although the predictive value of Bayesian analysis compared with frequentist approaches remains debated. Methods The SURTAVI trial randomized 1,660 patients. An interim analysis was performed 1 year after the 1,400th patient was treated to estimate the primary 2-year endpoint of all-cause mortality or disabling strokes for all patients. Results The Kaplan-Meier rate for the complete 2-year primary endpoint was 12.7% in the TAVR group and 12.6% in the surgery group (0.0% difference; 95% confidence interval: −3.4% to 3.5%), compared with 12.6% with TAVR and 14.0% with surgery (−1.4% difference; Bayesian credible interval: −5.2% to 2.3%) in the interim Bayesian analysis. A comparison of individual clinical, hemodynamic, and quality-of-life endpoints using Bayesian and frequentist methods found no significant differences. Conclusions The complete analysis of all patients with aortic stenosis at intermediate risk for surgery in the SURTAVI trial confirmed the noninferiority, with respect to the frequency of all-cause mortality or disabling stroke, of TAVR to surgery, as determined in the interim Bayesian analysis. Follow-up will extend out to 10 years.

Background— The risk for stroke after transcatheter aortic valve replacement (TAVR) is an important concern. Identification of predictors for stroke is likely to be a critical factor aiding patient selection and management as TAVR use becomes widespread. Methods and Results— Patients enrolled in the CoreValve US Extreme Risk and High Risk Pivotal Trials or Continued Access Study treated with the self-expanding CoreValve bioprosthesis were included in this analysis. The 1-year stroke rate after TAVR was 8.4%. Analysis of the stroke hazard rate identified an early phase (0–10 days; 4.1% of strokes) and a late phase (11–365 days; 4.3% of strokes). Baseline predictors of early stroke included National Institutes of Health stroke scale score >0, prior stroke, prior transient ischemic attack, peripheral vascular disease, absence of prior coronary artery bypass surgery, angina, low body mass index (2 ), and falls within the past 6 months. Significant procedural predictors were total time in the catheterization laboratory or operating room, delivery catheter in the body time, rapid pacing used during valvuloplasty, and repositioning of the prosthesis. Predictors of stroke between 11 and 365 days were small body surface area, severe aortic calcification, and falls within the past 6 months. There were no significant imaging predictors of early or late stroke. Conclusions— Predictors of early stroke after TAVR included clinical and procedural factors; predictors of later stroke were limited to patient but not anatomic characteristics. These findings indicate that further refinement of imaging to identify anatomic factors predisposing to embolization may help improve stroke prediction in patients undergoing TAVR. Clinical Trial Registrations— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT01240902, NCT01531374.

Rationale: A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function. Objective: Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options. Methods and Results: In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×10 5 or 5×10 5 cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P =0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P =0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P =0.014; 12 months: 140±171 versus 58±146 seconds, P =0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients. Conclusions: Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (10 5 cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.

The modifying effect of diethyl maleate (DEM) on gastric tumor development was studied in rats initially given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and hypertonic sodium chloride (H-NaCl 10% or 5%). Groups of animals were maintained with or without a 0.2% DEM dietary supplement after treatment with MNNG and H-NaCl and sacrificed at week 20. Forestomachs and livers cytosolic NAD(P)H:quinone-acceptor oxidoreductase (QR) activity was also analyzed. The incidences of forestomach severe hyperplasias in the MNNG + H-NaCl --DEM groups were also significantly higher than in the MNNG + H-NaCl alone group (P0.01 and P0.05 for 5% and 10% groups, respectively). Similarly, in the glandular stomach, the numbers of preneoplastic pepsinogen 1 altered pyloric glands (PAPGs) in the MNNG + H-NaCl --DEM groups were significantly increased (P0.01 for both concentrations). The QR activities in the groups treated with DEM showed 2- to 3-fold increases as compared with the control level. The results indicate that treatment with 0.2% DEM after MNNG initiation exerts enhancing effects on both forestomach and glandular stomach carcinogenesis. Induction of QR, a Phase II enzyme, activity in the rat stomach by DEM may be associated with promotion of stomach carcinogenesis rather than inhibition.

We report helminthic infections in the liver and intestine of Rattus norvegicus captured in Chunchon, Korea from April to October, 1994. Out of 43 examined rats, eggs of Capillaria hepatica were found in 11, Hymenolepis diminuta in 14 and Taenia taeniaeformis metacestodes in 28. Those rats can be sources of zoonotic infections in the surveyed area.

Objectives The CoreValve Extreme Risk US Pivotal Trial enrolled patients with symptomatic severe aortic stenosis deemed unsuitable for surgical aortic valve replacement. Implants were attempted using transfemoral access (n = 489) or an alternative access (n = 150). In present analysis, we sought to examine the safety and efficacy of CoreValve transcatheter aortic valve replacement using alternative access. Methods The present study included 150 patients with prohibitive iliofemoral anatomy who were treated with the CoreValve transcatheter heart valve delivered by way of the subclavian artery (n = 70) or a direct aortic approach (n = 80). The echocardiograms were read by an independent core laboratory. The primary endpoint was all-cause mortality or major stroke at 12 months. Results The preoperative aortic valve area was 0.72 ± 0.27 cm 2 and mean aortic valve gradient was 49.5 ± 17.0 mm Hg. After the transcatheter aortic valve replacement, the effective aortic valve area was 1.82 ± 0.64 cm 2 at 1 month and 1.85 ± 0.51 cm 2 at 12 months. The mean aortic valve gradient was 9.7 ± 5.8 mm Hg at 30 days and 9.5 ± 5.7 mm Hg at 12 months. The death or major stroke rate was 15.3% at 30 days and 39.4% at 12 months. The individual rate of all-cause mortality and major stroke was 11.3% and 7.5% at 30 days and 36.0% and 9.1% at 12 months. Conclusions These data demonstrate that the CoreValve transcatheter heart valve delivered by an alternative access provides a suitable alternative for treatment of extreme risk patients with symptomatic severe aortic stenosis, who have prohibitive iliofemoral anatomy and no surgical options.