Publications

Background— Surveillance conventional coronary angiography (CCA) is recommended 2 to 6 months after stent-supported left main coronary artery (LMCA) percutaneous coronary intervention due to the unpredictable occurrence of in-stent restenosis (ISR), with its attendant risks. Multislice computed tomography (MSCT) is a promising technique for noninvasive coronary evaluation. We evaluated the diagnostic performance of high-resolution MSCT to detect ISR after stenting of the LMCA. Methods and Results— Seventy-four patients were prospectively identified from a consecutive patient population scheduled for follow-up CCA after LMCA stenting and underwent MSCT before CCA. Until August 2004, a 16-slice scanner was used (n=27), but we switched to the 64-slice scanner after that period (n=43). Patients with initial heart rates >65 bpm received β-blockers, which resulted in a mean periscan heart rate of 57±7 bpm. Among patients with technically adequate scans (n=70), MSCT correctly identified all patients with ISR (10 of 70) but misclassified 5 patients without ISR (false-positives). Overall, the accuracy of MSCT for detection of angiographic ISR was 93%. The sensitivity, specificity, and positive and negative predictive values were 100%, 91%, 67%, and 100%, respectively. When analysis was restricted to patients with stenting of the LMCA with or without extension into a single major side branch, accuracy was 98%. When both branches of the LMCA bifurcation were stented, accuracy was 83%. For the assessment of stent diameter and area, MSCT showed good correlation with intravascular ultrasound ( r =0.78 and 0.73, respectively). An intravascular ultrasound threshold value ≥1 mm was identified to reliably detect in-stent neointima hyperplasia with MSCT. Conclusions— Current MSCT technology, in combination with optimal heart rate control, allows reliable noninvasive evaluation of selected patients after LMCA stenting. MSCT is safe to exclude left main ISR and may therefore be an acceptable first-line alternative to CCA.

Both the sirolimus-(SES) and paclitaxel-eluting (PES) stents have been shown to reduce restenosis rates when used in relatively simple lesions. This study aimed to evaluate the results of a consecutive series of patients treated with drug-eluting stent implantation for de novo bifurcation lesions, and compared outcomes with respect to stenting strategy and stent type.From April 2002 to September 2003, all patients at our institution were treated with drug-eluting stent implantation. A consecutive series of 144 patients were treated for 167 de novo bifurcation lesions with SES, followed by 104 patients treated with PES for 113 lesions.Clinical follow-up at 6 months was obtained in 99% patients with survival-free of major adverse cardiac events (MACE) of 93.7% for SES versus 85.8% for PES, p=0.05. By multivariate analysis, factors predictive for MACE were age, diabetes mellitus, previous CABG, multivessel disease, treatment for acute myocardial infarction, and treatment with PES. Survival-free of target lesion revascularization (TLR) was 95.7% for SES versus 86.8% for PES, p=0.01, with stent type being the only independent predictor. Technique of stenting was not a predictor of either MACE or TLR.MACE rates for both the SES and PES are low compared with historical data of bare metal stents. The most effective techniques for bifurcation stenting remain undefined. Our data suggests a higher need for TLR for the PES compared with the SES, however further randomized studies are needed to fully evaluate both stenting strategy, and any difference between the stents.

Objectives : To determine the frequency and independent predictors of acute kidney injury (AKI) in addition to the prognostic implications of both AKI and periprocedural red blood cell (RBC) transfusions on 30 day and cumulative late mortality in patients undergoing transcatheter aortic valve implantation (TAVI). Background : RBC transfusions have been reported to predict AKI following TAVI. Data on the prognostic implications of both factors, however, are lacking. Methods : 126 consecutive patients underwent TAVI with the Medtronic CoreValve Revalving System. AKI was defined according to the valve academic research consortium definitions as an absolute increase in serum creatinine ≥0.3 mg dL −1 (≥26.4 μmol L −1 ) or a percentage increase ≥50% within 72 hr following TAVI. Results : Five patients on chronic haemodialysis and three intraprocedural deaths were excluded, leading to a final study population of 118 patients. AKI occurred in 19% of the patients necessitating temporary haemodialysis in 2%. Independent predictors of AKI included: previous myocardial infarction (OR: 5.72; 95% CI: 1.64–19.94), periprocedural (<24 hr) RBC transfusions (OR: 1.29; 95% CI: 1.01–1.70), postprocedural (<72 hr) leucocyte count (OR: 1.18; 95% CI: 1.02–1.37), and logistic EuroSCORE (OR: 1.08; 95% CI: 1.01–1.14). In patients with AKI, 30‐day mortality was 23% and cumulative late mortality (median: 13 months) was 55%. AKI (OR: 5.47; 95% CI: 1.23–24.21) and postprocedural leucocyte count (OR: 1.20; 95% CI: 1.03–1.38) were independent predictors of 30‐day mortality while AKI (HR: 2.79; 95% CI: 1.36–5.71) was the only independent predictor of late mortality. Conclusions : AKI following TAVI occurred in 19% of the patients. RBC transfusion was found to be an independent predictor of AKI, which in turn predicted both 30‐day and cumulative late mortality. © 2011 Wiley‐Liss, Inc.

Stimulation of HEL 299 cells with tumor necrosis factor α (TNF-α) or interleukin 1β (IL-1β) had no effect on M2 muscarinic receptor expression. However, the combination of these two cytokines markedly down-regulated muscarinic M2 receptor protein and mRNA expression and uncoupled M2 receptors from adenylyl cyclase. There was no effect of TNF-α and IL-1β on the m2 muscarinic receptor mRNA stability, and nuclear run-on assays showed reduced m2 receptor gene transcription. Sequential cytokine addition suggests that the synergy involves postreceptor events. Although the cAMP-dependent protein kinase inhibitor H8 provided a significant protection against receptor down-regulation, the protein kinase C inhibitor GF109203X had no effect. The ceramide analog C2-ceramide (N-acetylsphingosine) was without effect on m2 receptor expression. However, a strong synergistic effect was demonstrated when cells were treated with the combination of C2-ceramide and TNF-α or IL-1β. TNF-α and/or IL-1β combination also activated the 46- and 55-kDa c-Jun NH2-terminal protein kinases and to a lesser extent p42 and p44 mitogen-activated protein kinase isoforms. Cycloheximide abolished the TNF-α and IL-1β effect, suggesting that de novo protein synthesis is required for receptor down-regulation. These results suggest that the TNF-α and IL-1β synergize to induce transcriptional down-regulation of the M2 muscarinic receptor, which seems to be mediated through activation of both ceramide and cAMP-dependent protein kinase pathways. Furthermore, these results suggest that M2 receptor expression is under the control of a cytokine network. Stimulation of HEL 299 cells with tumor necrosis factor α (TNF-α) or interleukin 1β (IL-1β) had no effect on M2 muscarinic receptor expression. However, the combination of these two cytokines markedly down-regulated muscarinic M2 receptor protein and mRNA expression and uncoupled M2 receptors from adenylyl cyclase. There was no effect of TNF-α and IL-1β on the m2 muscarinic receptor mRNA stability, and nuclear run-on assays showed reduced m2 receptor gene transcription. Sequential cytokine addition suggests that the synergy involves postreceptor events. Although the cAMP-dependent protein kinase inhibitor H8 provided a significant protection against receptor down-regulation, the protein kinase C inhibitor GF109203X had no effect. The ceramide analog C2-ceramide (N-acetylsphingosine) was without effect on m2 receptor expression. However, a strong synergistic effect was demonstrated when cells were treated with the combination of C2-ceramide and TNF-α or IL-1β. TNF-α and/or IL-1β combination also activated the 46- and 55-kDa c-Jun NH2-terminal protein kinases and to a lesser extent p42 and p44 mitogen-activated protein kinase isoforms. Cycloheximide abolished the TNF-α and IL-1β effect, suggesting that de novo protein synthesis is required for receptor down-regulation. These results suggest that the TNF-α and IL-1β synergize to induce transcriptional down-regulation of the M2 muscarinic receptor, which seems to be mediated through activation of both ceramide and cAMP-dependent protein kinase pathways. Furthermore, these results suggest that M2 receptor expression is under the control of a cytokine network.

<h3>Importance</h3> Left atrial appendage occlusion (LAAO) has emerged as an alternative to anticoagulation for patients with atrial fibrillation. However, the performance of LAAO among East Asian patients is unknown. <h3>Objective</h3> To document the procedural success rate and configurations, major adverse event rates, and antithrombotic medication regimens during and after LAAO procedures among patients in China. <h3>Design, Setting, and Participants</h3> In this cohort study, consecutive patients from 39 Chinese centers undergoing LAAO were prospectively enrolled between April 1, 2019, and October 31, 2020. Periprocedural and intraprocedural techniques and postprocedural medications were left to the surgeon's discretion. Data were analyzed from July 1 to November 1, 2021. <h3>Exposure</h3> LAAO for patients with atrial fibrillation. <h3>Main Outcomes and Measures</h3> The main outcomes were procedural success and complication rates periprocedure and major adverse event rates of death, stroke, systemic embolism, and bleeding events at 30 days postprocedure; the composite end point of death, stroke, and systemic embolism was also analyzed. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess the associations of periprocedural techniques (types of anesthesia, intraprocedural imaging modalities, and combined ablation procedure) with 30-day adverse events. <h3>Results</h3> Among 3096 enrolled participants, 1782 participants (57.6%) were men, and the mean (SD) age was 69 (9) years. Participants had a high risk of stroke (mean [SD] cardiovascular risk score, 4.0 [1.8]) and a moderate-to-high risk of bleeding (mean [SD] bleeding risk score, 2.4 [1.2]). A total of 1287 procedures (41.6%) were performed under local anesthesia, while 493 procedures (15.9%) used only fluoroscopy guidance. In 1297 procedures (41.9%), LAAO implantation was combined with radiofrequency ablation or cryoablation for atrial fibrillation. Procedural success was achieved in 3032 patients (97.9%). At 30-day follow-up, the rate of the composite end point of death, stroke, or systemic embolism was 0.52% (95% CI, 0.32%-0.84%), and the rate of any life-threatening or major bleeding was 1.23% (95% CI, 0.90%-1.68%). No significant associations were observed between the procedural success or 30-day adverse events and the types of anesthesia (general or local), intraprocedural imaging (transesophageal echocardiography, fluoroscopy, or intracardiac echocardiography), or whether a combined ablation procedure was performed or not. In centers performing at least 40 procedures per year, compared with those performing fewer than 40 procedures per year, procedural success was significantly higher (adjusted odd ratio [aOR], 1.97; 95% CI, 1.01-3.53;<i>P</i> = .02) and risk of life-threatening or major bleeding was significantly lower (aOR, 0.42; 95% CI, 0.21-0.87;<i>P</i> = .02). <h3>Conclusions and Relevance</h3> These findings suggest that patients with a high risk of stroke and moderate to high risk of bleeding who underwent implantation of a LAAO device in Chinese centers had high rates of procedural success and low rates of short-term ischemic and bleeding events.

The aim of this study was to determine six months restenosis rate measured by off-line quantitative coronary angiography, and to assess the efficacy and safety of newly developed six cells Tsunami stent system for the treatment of symptomatic, de novo, native coronary artery lesions.Between January and August 2001, 100 patients with 120 lesions were included at four clinical sites in this prospective, non-randomized, single arm study. In 35% of the patients two or more stents were implanted, 15% of the lesions were stented with more than one stent and 46% of the lesions were in small vessels (<or= 2.75 mm). The Tsunami stent was available in 10, 15, 20 and 30 mm, length, and 3, 3.5 and 4 mm diameter. Angiographic success rate for stented lesions was 100% (residual diameter stenosis <or= 30%) and procedural success rate was 98%. Mean reference vessel diameter by QCA was 2.83 +/- 0.52, and post-procedural minimal lumen diameter was 2.59+/-0.4. Six months angiographic follow-up was available for 81% of the patients and revealed an in-stent restenosis rate of 13.8% for all lesions and 7.4% for single stented lesions. At 30 days 98% and at 6 months 88% of the patients remained free of major adverse cardiac events.Based on the clinical and angiographic results of the present study we can conclude that the Tsunami stent provides safe and effective percutaneous treatment of obstructive coronary artery disease.

Objectives : To study the effect of endothelial progenitor cell (EPC) capture on the vascular response to coronary stenting. Background : The introduction of drug‐eluting stents has reduced the need for target lesion revascularization, but their effect on delayed healing, inflammation, and vascular dysfunction has emphasized the need to design strategies that improve current DES. One such strategy is to improve endothelialization by capturing CD34‐positive cells (EPC) by the stent surface. The first human clinical trial using coronary EPC capture stents showed stent safety but neointimal thickness (NIT) was not reduced compared to bare metal stents (BMS). To understand these responses we studied the coronary response to the EPC capture stent in swine. Methods and Results : The stent, coated with murine antihuman monoclonal CD34 antibodies, was assessed with QCA guided stent implantation in normal swine coronary arteries for early endothelialization at 2 and 5 days, and NIT at 28 and 90 days in comparison to control stents carrying a non‐specific murine antibody or to BMS. The main finding was that while the EPC capture stent significantly improved early endothelialization it did not reduce NIT at 28 and 90 days. Conclusions : The EPC capture stent improves early endothelialization in swine but this does not affect neointimal thickness as compared to control stents at 28 and 90 days. © 2011 Wiley Periodicals, Inc.

Purpose : To measure the effect of cardiac motion on coronary artery stent position during the cardiac cycle as a first step toward exploring the feasibility of stereotactic external beam radiation therapy targeted at restenotic stented coronary arteries. Methods and Materials : The three-dimensional (3D) position of eight coronary artery stents in 8 patients immobilized in a stereotactic body frame was studied noninvasively by single-breathhold ECG-gated multislice spiral computed tomography (MSCT) during 10 retrospectively selected phases, equally distributed throughout the R-R interval of consecutive cardiac cycles. The volume encompassing all measured 3D positions of the stent was measured. Results : Stent volumes measured by MSCT closely agreed with measurements by quantitative coronary angiography (r > 0.99). The mean of the maximum 3D stent center of mass displacement between any two phases during the cardiac cycle for all eight coronary arteries was 7.5 mm (range 3.3–20.5 mm) in the lateral direction, 8.6 mm (range 2.7–21.6 mm) in the ventrodorsal direction, and 8.2 mm (range 2.5–19.7 mm) in the craniocaudal direction. As was anticipated, the volume encompassing all measured 3D positions of the stent represented only a fraction of the whole heart volume in all patients, i.e., less than 0.6%. Conclusions : ECG-gated MSCT allowed the measurement of the volume encompassing multiphase 3D positions of coronary artery stents during the cardiac cycle. This volume, a measure of the cardiac motion effect on coronary artery stent position during the cardiac cycle, represents a moving gross target for stereotactic external beam radiation therapy.

BackgroundMedication adherence is challenging for adolescents. In mild asthma, as-needed budesonide-formoterol (BUD-FORM) reduces severe exacerbations compared with as-needed short-acting beta2-agonists, similar to the reduction with maintenance budesonide.ObjectiveThis post hoc pooled analysis of Symbicort Given as-needed in Mild Asthma (SYGMA) 1 and 2 assessed the efficacy and safety of as-needed BUD-FORM in adolescents.MethodsSYGMA 1 and 2 were 52-week, double-blind studies (NCT022149199; NCT02224157) in patients 12 years or older with mild asthma. Patients were randomized to twice-daily placebo + as-needed BUD-FORM 200/6 μg, twice-daily BUD 200 μg + as-needed terbutaline (BUD maintenance), or twice-daily placebo + as-needed terbutaline 0.5 mg (SYGMA 1 only). Annualized severe exacerbation rates, maintenance treatment adherence, and safety (including change in height) were compared between treatment groups in adolescents (aged ≥12 to <18 years).ResultsSevere exacerbation rate was similar with as-needed BUD-FORM and BUD maintenance (pooled analysis: 0.08 vs 0.07/y; P = .634), and was significantly lower with as-needed BUD-FORM versus as-needed terbutaline (SYGMA 1: 0.04 vs 0.17/y; P = .005). Median adherence was 73% in SYGMA 1 and 51% in SYGMA 2. Change in height from baseline in adolescents aged ≥12 years to <14 years was significantly greater with as-needed BUD-FORM (4.8 cm) versus BUD maintenance (3.9 cm) (pooled: P < .046), and was similar between as-needed BUD-FORM (4.5 cm) and as-needed terbutaline (4.1 cm) (SYGMA 1: P = .500). No new or unexpected safety concerns were identified.ConclusionsIn adolescents with mild asthma, as-needed BUD-FORM was superior to as-needed terbutaline for severe exacerbation reduction, with similar efficacy to BUD maintenance. As-needed BUD-FORM provides an alternative treatment option for adolescents with mild asthma, without needing daily treatment. Medication adherence is challenging for adolescents. In mild asthma, as-needed budesonide-formoterol (BUD-FORM) reduces severe exacerbations compared with as-needed short-acting beta2-agonists, similar to the reduction with maintenance budesonide. This post hoc pooled analysis of Symbicort Given as-needed in Mild Asthma (SYGMA) 1 and 2 assessed the efficacy and safety of as-needed BUD-FORM in adolescents. SYGMA 1 and 2 were 52-week, double-blind studies (NCT022149199; NCT02224157) in patients 12 years or older with mild asthma. Patients were randomized to twice-daily placebo + as-needed BUD-FORM 200/6 μg, twice-daily BUD 200 μg + as-needed terbutaline (BUD maintenance), or twice-daily placebo + as-needed terbutaline 0.5 mg (SYGMA 1 only). Annualized severe exacerbation rates, maintenance treatment adherence, and safety (including change in height) were compared between treatment groups in adolescents (aged ≥12 to <18 years). Severe exacerbation rate was similar with as-needed BUD-FORM and BUD maintenance (pooled analysis: 0.08 vs 0.07/y; P = .634), and was significantly lower with as-needed BUD-FORM versus as-needed terbutaline (SYGMA 1: 0.04 vs 0.17/y; P = .005). Median adherence was 73% in SYGMA 1 and 51% in SYGMA 2. Change in height from baseline in adolescents aged ≥12 years to <14 years was significantly greater with as-needed BUD-FORM (4.8 cm) versus BUD maintenance (3.9 cm) (pooled: P < .046), and was similar between as-needed BUD-FORM (4.5 cm) and as-needed terbutaline (4.1 cm) (SYGMA 1: P = .500). No new or unexpected safety concerns were identified. In adolescents with mild asthma, as-needed BUD-FORM was superior to as-needed terbutaline for severe exacerbation reduction, with similar efficacy to BUD maintenance. As-needed BUD-FORM provides an alternative treatment option for adolescents with mild asthma, without needing daily treatment.