Symptomatic aortic stenosis remains a surgical disease, with aortic valve replacement resulting in symptom reduction and improvement in survival. For patients who are deemed a higher surgical risk, ...Transcatheter aortic-valve replacement (TAVR) is a viable, less invasive and increasingly common alternative. The study compares early outcomes in patients treated within one year of the commencement of TAVR program in a community hospital against outcomes of TAVR patients from nationwide reported data (Society of Thoracic Surgeons/ American College of Cardiology TVT registry). Preoperative characteristics and standardized procedural outcomes of all patients who underwent TAVR in Cape Cod Hospital between June 2015 and May 2016 (n = 62, CCH group) were compared using standardized data format to those of TAVR patients operated during the same time period in other centers within the United States participating in the STS/ACC TVT Registry (n = 24,497, USA group). Most preoperative patient characteristics were similar between groups. However, CCH patients were older (age≥80 years: 77.4% versus 64.3%, p = 0.032) and more likely to be non-elective cases (37.1% versus 9.7%, p<0.001). All 62 TAVR procedures in CCH were performed in the catheterization laboratory unlike most (89.7%) of the procedures in the USA group that were performed in hybrid rooms. A larger proportion of patients in the USA registry underwent TAVR under general anesthesia (78.2% vs.37.1%, P<0.001). Early aortic valve re- intervention rate was 0/62 (0%) in the CCH group VS. 74/ 24,497 (0.3%) in the USA group. In hospital mortality, which was defined as death of any cause during thirty days from date of operation, (CCH: 0% vs. USA: 2.5%, p = 0.410) and occurrence of early adverse events (including postoperative para-valvular leaks, conduction defects requiring pacemakers, neurologic and renal complications) were similar in the two groups. The study concludes that with specific team training and co-ordination, and with active support of experienced personnel, high risk patients with severe aortic valve stenosis can be managed safely with a TAVR procedure in a community hospital.
Trans-catheter aortic valve replacement (TAVR) has become an alternative to surgical aortic valve replacement (SAVR) in high and intermediate risk patients with aortic stenosis. TAVR programs are ...spreading from large referral centers and being established in community based institutions. The purpose of this study was to compare the outcomes of TAVR to those of SAVR in a community hospital.A historical cohort study of patients with aortic stenosis and pre-post procedure echocardiography data who underwent SAVR or TAVR in Cape Cod Hospital between January 2014 and December 2016. Patient characteristics and procedure outcomes were compared between the two procedures.The study included 230 patients, of them 111 underwent SAVR and 119 underwent TAVR. None of the patients died during the 30 days after the procedure. TAVR patients had higher rates of postoperative mild+ aortic regurgitation (AR) (29.4% vs 12.6%, P = .002), postoperative atrial ventricular blocks (11.8% vs 0.9%, P = .001), and more often need an implantation of pacemaker (16.8% vs 0.9%, P < .001). Postoperative mean gradient of SAVR patients was higher (median 14 vs 11 mm Hg, P = .001) and atrial fibrillation postoperatively was more frequent (18.9% vs 2.5%, P < .001). Length of stay after procedure was shorter in TAVR patients (median 2 vs 4 days, P < .001).After controlling for confounders, the use of TAVR was associated with an increased risk for postoperative pacemaker implantation (OR = 16.3, 95%CI 1.91-138.7, P = .011), lower mean gradient (-4.327, 95%CI -7.68 to -0.98, P = .011), and lower risk for atrial fibrillation (OR = 0.11, 95%CI 0.03-0.38, P = .001), but not with postoperative AR (OR = 0.84, 95%CI 0.22-3.13, P = .789).In conclusion, short-term mortality was not reported in SAVR or TAVR patients. However, TAVR was associated with an increased risk for postoperative pacemaker implantation but with a lower risk for atrial fibrillation. Aortic valves implanted through a trans-catheter approach are also associated with a better hemodynamic performance.
In patients with moderate- and high-risk acute coronary syndromes (ACS) who undergo an early, invasive treatment strategy, current guidelines recommend administration of platelet glycoprotein ...IIb/IIIa (Gp IIb/IIIa) inhibitors, either upstream to all patients prior to angiography or deferred for selective use in the catheterization laboratory just prior to angioplasty. The preferred approach is undetermined.
To determine the optimal strategy for the use of Gp IIb/IIIa inhibitors in patients with moderate- and high-risk ACS undergoing an early, invasive treatment strategy.
Prospective, randomized, open-label trial with 30-day clinical follow-up.
Four hundred fifty academic and community-based institutions in 17 countries.
A total of 9207 patients with moderate- and high-risk ACS undergoing an invasive treatment strategy.
Patients were randomly assigned to receive either routine upstream (n=4605) or deferred selective (n=4602) Gp IIb/IIIa inhibitor administration, respectively.
The primary outcome was assessment of noninferiority of deferred Gp IIb/IIIa inhibitor use compared with upstream administration for the prevention of composite ischemic events (death, myocardial infarction, or unplanned revascularization for ischemia) at 30 days, using a 1-sided alpha level of .025. Major secondary end points included noninferiority or superiority of major bleeding and net clinical outcomes (composite ischemia or major bleeding).
Glycoprotein IIb/IIIa inhibitors were used more frequently (98.3% vs 55.7%, respectively) and for a significantly longer duration (median, 18.3 vs 13.1 hours; P<.001) in patients in the upstream group compared with the deferred group. Composite ischemia at 30 days occurred in 7.9% of patients assigned to deferred use compared with 7.1% of patients assigned to upstream administration (relative risk, 1.12; 95% confidence interval, 0.97-1.29; P = .044 for noninferiority; P = .13 for superiority); as such, the criterion for noninferiority was not met. Deferred use compared with upstream use resulted in reduced 30-day rates of major bleeding (4.9% vs 6.1%, respectively; P<.001 for noninferiority; P = .009 for superiority) and similar rates of net clinical outcomes (11.7% vs 11.7%; P<.001 for noninferiority; P = .93 for superiority).
Among patients with moderate- and high-risk ACS undergoing an invasive treatment strategy, deferring the routine upstream use of Gp IIb/IIIa inhibitors for selective administration in the cardiac catheterization laboratory only to patients undergoing percutaneous coronary intervention resulted in a numerical increase in composite ischemia that, while not statistically significant, did not meet the criterion for noninferiority. This finding was offset by a significant reduction in major bleeding.
ClinicalTrials.gov Identifier: NCT00093158.
Abstract Background Contrast-induced nephropathy (CIN) is a frequent complication following angiographic procedures with significant impact on healthcare costs, and long-term outcomes. Multiple ...reno-protective strategies have been studied but few have shown benefit in prospective randomized studies beyond limiting the exposure to iodinated contrast and adequate intravenous. We studied the performance and safety of a novel system designed to achieve precise real-time high volume fluid balance using a closed loop hydration monitoring and infusion system. Methods This prospective, multi-center, FDA approved phase II feasibility study was designed to evaluate the safety and the performance of the RenalGuard matched hydration system. Between October 2006 and November 2007, twenty-three subjects at high risk for CIN (with an estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 ) undergoing diagnostic or therapeutic catheterization were treated with the system. The primary endpoint of the study was defined as the ability of the system to effectively dynamically match fluid administration to urine output. Results The 23 subjects at high risk for CIN enrolled had a mean ± SD eGFR of 39 ± 9.3. Patients achieved an hourly urine flow rate of 620 ± 400 ml/h. The system had a mean effectiveness rate of 99.9% over the duration of therapy with an average saline volume infused of 3825 ml closely matched, minute to minute, to urine output of 3579 ml. There were no major device-related complications from the experimental therapy, though one patient developed hypokalemia requiring replacement. Two subjects (9.5%) developed CIN as defined by > 0.5 mg/dl or > 25% rise in serum creatinine at 48–60 h post contrast administration when compared with the baseline. Conclusion The study confirmed that the RenalGuardTM system is safe and dynamically balances volume hydration with urine production. Further randomized studies are needed to confirm the efficacy of the system in reducing the incidence of CIN.
Background PROMUS Element (PE) Plus, a thin-strut everolimus-eluting platinum chromium coronary artery stent, has shown favorable outcomes up to 3 years after implantation in a large post-approval ...study representative of clinical practice. Analyses of the 4-year clinical outcomes will provide insight into the long term safety and efficacy of the PE Plus stent in a broad, unselected patient population.
Melorheostosis is a sporadic disease of uncertain etiology characterized by asymmetric bone overgrowth and functional impairment. Using whole exome sequencing, we identify somatic mosaic MAP2K1 ...mutations in affected, but not unaffected, bone of eight unrelated patients with melorheostosis. The activating mutations (Q56P, K57E and K57N) cluster tightly in the MEK1 negative regulatory domain. Affected bone displays a mosaic pattern of increased p-ERK1/2 in osteoblast immunohistochemistry. Osteoblasts cultured from affected bone comprise two populations with distinct p-ERK1/2 levels by flow cytometry, enhanced ERK1/2 activation, and increased cell proliferation. However, these MAP2K1 mutations inhibit BMP2-mediated osteoblast mineralization and differentiation in vitro, underlying the markedly increased osteoid detected in affected bone histology. Mosaicism is also detected in the skin overlying bone lesions in four of five patients tested. Our data show that the MAP2K1 oncogene is important in human bone formation and implicate MEK1 inhibition as a potential treatment avenue for melorheostosis.
Melorheostosis is a rare sclerosing dysostosis characterized by asymmetric exuberant bone formation. Recently, we reported that somatic mosaicism for MAP2K1-activating mutations causes radiographical ..."dripping candle wax" melorheostosis. We now report somatic SMAD3 mutations in bone lesions of four unrelated patients with endosteal pattern melorheostosis. In vitro, the SMAD3 mutations stimulated the TGF-β pathway in osteoblasts, enhanced nuclear translocation and target gene expression, and inhibited proliferation. Osteoblast differentiation and mineralization were stimulated by the SMAD3 mutation, consistent with higher mineralization in affected than in unaffected bone, but differing from MAP2K1 mutation-positive melorheostosis. Conversely, osteoblast differentiation and mineralization were inhibited when osteogenesis of affected osteoblasts was driven in the presence of BMP2. Transcriptome profiling displayed that TGF-β pathway activation and ossification-related processes were significantly influenced by the SMAD3 mutation. Co-expression clustering illuminated melorheostosis pathophysiology, including alterations in ECM organization, cell growth, and interferon signaling. These data reveal antagonism of TGF-β/SMAD3 activation by BMP signaling in SMAD3 mutation-positive endosteal melorheostosis, which may guide future therapies.
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