REduction of THRomboembolic EVents during Ablation using the laserballoon: The RETHREVA registry.

INTRODUCTION: Cerebral events (CEs), including silent (SCEs), are a known complication of left atrial catheter ablation (LACA) in patients with atrial fibrillation. The aim of this prospective registry was to gain more information about CEs during laserballoon LACA and to reduce the risk of their occurrence. METHODS AND RESULTS: We enrolled 74 patients (age 61 ± 11 years; 74% male; CHA2 DS2 -VASc 1.9 ± 1.4). Cerebral MRI (1.5 Tesla) was performed to detect CEs. ASPItest identified aspirin-resistant patients (ARPs). All bleeding complications were recorded. Due to an initial high CE rate, we evolved our clinical procedure step-by-step arriving at an optimized protocol: -Group 1: heparin after single transseptal puncture (TP), activated clotting time (ACT) > 300 seconds (CE: 64.3%). -Group 2: heparin after double TP, ACT > 300 seconds; 2a without (CE: 45.5%, RRR: -29.2%) and 2b with additional intravenous aspirin (CE: 36.4%, RRR: -43.4%; excluding ARP: 30%, RRR: -53.3%). -Group 3: heparin before double TP, ACT > 350 seconds; 3a without (CE: 54.5%, RRR: -15.2%) and 3b with aspirin (CE: 18.5%, RRR: -71.2%; excluding ARP: 8.7%, RRR: -86.5%). Larger LA diameter > 44 mm (OR: 1.149, P  =  0.005) and no aspirin use (OR: 4.308, P  =  0.008) were CE risk factors in multivariate logistic regression. In those patients receiving aspirin, aspirin resistance (OR: 22.4, P  =  0.011) was an exceptionally strong risk factor. CONCLUSION: These data support the use of intravenous aspirin including monitoring of aspirin resistance in addition to ACT-guided heparin. An optimized protocol of heparin before TP, double TP, and intravenous aspirin in non-ARP resulted in a significantly lowered CE incidence and severity.

Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial.

BACKGROUND: In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up. METHODS: The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥ 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774. FINDINGS: After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001). INTERPRETATION: The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients. FUNDING: St Jude Medical, Friends of the Heart Foundation, and Medtronic.

First generation versus second generation drug-eluting stents for the treatment of bifurcations: 5-year follow-up of the LEADERS all-comers randomized trial.

BACKGROUND: Historically, percutaneous coronary intervention (PCI) of bifurcation lesions was associated with worse procedural and clinical outcomes when compared with PCI of non-bifurcation lesions. Newer generation drug-eluting stents (DES) might improve long-term clinical outcomes after bifurcation PCI. METHODS AND RESULTS: The LEADERS trial was a 10-center, assessor-blind, non-inferiority, all-comers trial, randomizing 1,707 patients to treatment with a biolimus A9(TM) -eluting stent (BES) with an abluminal biodegradable polymer or a sirolimus-eluting stent (SES) with a durable polymer (ClinicalTrials.gov Identifier: NCT00389220). Five-year clinical outcomes were compared between patients with and without bifurcation lesions and between BES and SES in the bifurcation lesion subgroup. There were 497 (29%) patients with at least 1 bifurcation lesion (BES = 258; SES = 239). At 5-year follow-up, the composite endpoint of cardiac death, myocardial infarction (MI) and clinically-indicated (CI) target vessel revascularization (TVR) was observed more frequently in the bifurcation group (26.6% vs. 22.4%, P = 0.049). Within the bifurcation lesion subgroup, no differences were observed in (cardiac) death or MI rates between BES and SES. However, CI target lesion revascularization (TLR) (10.1% vs. 15.9%, P = 0.0495), and CI TVR (12.0% vs. 19.2%, P = 0.023) rates were significantly lower in the BES group. Definite/probable stent thrombosis (ST) rate was numerically lower in the BES group (3.1% vs. 5.9%, P = 0.15). Very late (>1 year) definite/probable ST rates trended to be lower with BES (0.4% vs. 3.1%, P = 0.057). CONCLUSIONS: In the treatment of bifurcation lesions, use of BES led to superior long-term efficacy compared with SES. Safety outcomes were comparable between BES and SES, with an observed trend toward a lower rate of very late definite/probable ST between 1 and 5 years with the BES. © 2015 Wiley Periodicals, Inc.

Reasons reported by African ophthalmologists for staying in Africa and for considering migrating.

In sub-Sahara Africa, the shortage of ophthalmologists is a major obstacle in the struggle of fighting preventable blindness. Migration of well-trained ophthalmologists has an additional negative effect on the low number of caregivers. However, to date, the reasons affecting migration of ophthalmologists have not been completely understood. The present study evaluates reasons reported by ophthalmologists for staying in their current work setting/country and potential reasons why they might consider migrating. In the years 2009-2011, after approval was obtained from the Institutional Review Board, a questionnaire evaluating reasons for and against migration of ophthalmologists was distributed to the participants of 2-week courses in Ethiopia, Cameroon and Kenya providing continuing medical education in the field of ophthalmology. A total of 84 ophthalmologists participated in this survey. The main reasons for staying in their current region/country were good working conditions, commitment to help, possibility of further training, familial ties and general feeling of satisfaction. Professional development elsewhere and better income abroad were named as the main reasons for considering migration. Almost half of the survey participants reported good infrastructure, equipment, and consumables, which is encouraging. Programs aimed at continuing medical education of ophthalmologists to enable professional development may have an appropriate role in the establishment of an ophthalmic infrastructure which can meet patients' needs.

Myocardial injury after orbital atherectomy and its association with coronary lesion length.

BACKGROUND: Limited data are available regarding myocardial injury and its risk factors in percutaneous coronary interventions (PCI) of severe calcified lesions using orbital atherectomy (OA). METHODS: Patients who underwent OA at our institution were retrospectively enrolled into the present registry. High-sensitive Troponin I (hsTroponin I), EKG and echocardiography were used to assess myocardial injury after the procedure. RESULTS: A total of 27 patients between who underwent OA between January 2022 and June 2023 were included. Myocardial injury (elevation of hsTroponin I above the 99th percentile upper reference limit) occurred in all patients. Median hsTroponin I on the first day after the procedure was 1093 (557-4037) ng/l with a minimum of 86 ng/l and a maximum of 25,756 ng/l. Myocardial infarction occurred in two patients (7 %), who had severe coronary dissection after OA. Lesions were longer (47 [38-52] mm vs. 20 [14-47] mm; p = 0.009) in patients with hsTroponin I levels above the median compared to those with levels below. Furthermore, a moderate correlation between hsTroponin I and lesion length was detected (r = 0.54; p = 0.004). CONCLUSIONS: In the present study myocardial injury occurred in all patients after OA without loss of viable myocardium in the majority of patients. Lesions length was found to be a significant factor associated with markedly increased hsTroponin I after the OA procedure.

Comparison of zotarolimus-eluting and everolimus-eluting coronary stents.

BACKGROUND: New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration. METHODS: In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months. RESULTS: At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (+/-SD) of in-stent stenosis (21.65+/-14.42% for zotarolimus vs. 19.76+/-14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27+/-0.43 mm in the zotarolimus-stent group versus 0.19+/-0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events. CONCLUSIONS: At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084.)

Low-dose transscleral diode laser cyclophotocoagulation (TSCPC) as a potential single treatment for primary open-angle glaucoma (POAG) in Malawi?

PURPOSE: To investigate if low-dose 810 nm transscleral cyclophotocoagulation (TSCPC) can be used as single treatment in Malawian glaucoma patients. METHODS: Forty-seven eyes of 28 patients with primary open-angle and pseudoexfoliation glaucoma were treated with TSCPC using 12 spots with 900 mW, 2,000 ms (1.8 J per spot); six spots in the upper half, six in the lower by sparing the 3 and 9 o'clock positions ±20°. Intraocular pressure (IOP) and uncorrected visual acuity (UVA) were measured by an independent examiner preoperatively, on the first postoperative day, after 2 weeks, and after 3 months. RESULTS: Twenty-four (86%) and 18 (64%) of 28 patients (31 of 47 eyes; 66%) completed follow-up at 2 weeks and at 3 months respectively. After a single treatment session, IOP decreased by at least 25 % in 88% (21 of 24) after 2 weeks, and in 50% (nine of 18) of patients after 3 months. Mean IOP was 38.5 mmHg before TSCPC, 23.5 mmHg (p < 0.001) after 1 day, 24.5 mmHg (p < 0.001) after 2 weeks, and 35.6 mmHg (p = 0.37) after 3 months. In three patients, however, IOP increased after 3 months to levels significantly higher than before TSCPC. CONCLUSION: Low-dose TSCPC caused a significant IOP lowering for up to 2 weeks (15 mmHg less from baseline) in most patients. After 3 months, this effect was stable in 50% of patients; in the other half, IOP nearly returned back to baseline.

Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial.

BACKGROUND: The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. METHODS: We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS: 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7%) patients versus 192 (22·6%) patients (rate ratios [RR] 0·81, 95% CI 0·66-1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35-1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95% CI 0·06-0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51-1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive (p(interaction)=0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0·86 (0·41-1·80) during the first year and 0·17 (0·04-0·78) during subsequent years (p(interaction)=0·049). INTERPRETATION: Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. FUNDING: Biosensors Europe SA, Switzerland.

Fractional flow reserve versus angiography for guiding percutaneous coronary intervention.

BACKGROUND: In patients with multivessel coronary artery disease who are undergoing percutaneous coronary intervention (PCI), coronary angiography is the standard method for guiding the placement of the stent. It is unclear whether routine measurement of fractional flow reserve (FFR; the ratio of maximal blood flow in a stenotic artery to normal maximal flow), in addition to angiography, improves outcomes. METHODS: In 20 medical centers in the United States and Europe, we randomly assigned 1005 patients with multivessel coronary artery disease to undergo PCI with implantation of drug-eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80 or less. The primary end point was the rate of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. RESULTS: The mean (+/-SD) number of indicated lesions per patient was 2.7+/-0.9 in the angiography group and 2.8+/-1.0 in the FFR group (P=0.34). The number of stents used per patient was 2.7+/-1.2 and 1.9+/-1.3, respectively (P<0.001). The 1-year event rate was 18.3% (91 patients) in the angiography group and 13.2% (67 patients) in the FFR group (P=0.02). Seventy-eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group (P=0.20). CONCLUSIONS: Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. (ClinicalTrials.gov number, NCT00267774.)

Five-year results of the Multicenter Randomized Controlled Open-Label Study of the CYPHER Sirolimus-Eluting Stent in the Treatment of Diabetic Patients with De Novo Native Coronary Artery Lesions (SCORPIUS) study: a German multicenter investigation on the effectiveness of sirolimus-eluting stents in diabetic patients.

BACKGROUND: Because a delayed arterial healing response after drug-eluting stent implantation has raised concerns about safety in diabetic patients, long-term effects of treatment with sirolimus-eluting stent (SES), as compared with bare-metal stent (BMS), have to be established. The aim of the 5-year follow-up of the randomized, controlled, open-label multicenter SCORPIUS study was to assess long-term safety and efficacy of the CYPHER (Cordis, Johnson & Johnson, Bridgewater, NJ) SES in percutaneous coronary intervention of diabetic patients. METHODS: A total of 190 patients with type 2 diabetes mellitus were randomized to receive either a SES (n = 95) or a BMS (n = 95). Dual-antiplatelet therapy (aspirin plus clopidogrel) was prescribed for at least 6 months. Clinical follow-up data were scheduled at 1, 8, and 12 months and 5 years. RESULTS: Treatment with SES resulted in a 16% decrease in the rate of major adverse cardiac events (36% vs 52%; hazard ratio 0.6, 95% CI 0.4-0.9; P = .02). This reduction in major adverse cardiac events with SES at 5 years was mostly attributable to a lower number of repeat target lesion revascularization (13% vs 29%; hazard ratio 0.4, 95% CI 0.2-0.7; P = .003). No differences between groups were observed for safety end points (all-cause mortality 21% vs 21%, cardiac death 15% vs 13%, repeat myocardial infarction 8% vs 9%, and stent thrombosis 5% vs 6%) at 5 years. CONCLUSIONS: The 5-year follow-up of the SCORPIUS trial demonstrates the long-term antirestenotic efficacy of SES in diabetic patients with significantly reduced target lesion revascularization and comparable rates of mortality, myocardial infarction, and stent thrombosis compared with BMS.

CD34+CD140b+ cells and circulating CXCL12 correlate with the angiographically assessed severity of cardiac allograft vasculopathy.

AIMS: We sought to determine whether circulating vascular progenitor cells, such as endothelial progenitor cells (EPCs) or smooth muscle progenitor cells (SPCs), were associated with the severity of cardiac allograft vasculopathy (CAV). METHODS AND RESULTS: CD34(+)CD140b(+) SPCs and CD34(+)KDR(+) EPCs were measured in the peripheral circulation of 187 adult heart transplant recipients by flow cytometry. Cardiac allograft vasculopathy was quantified by angiography using a CAV-specific scoring system. Cardiac allograft vasculopathy was present in 84 patients (44.7%) and was classified as mild in 59 and severe in 25 cases. Circulating SPCs were more frequently detectable in CAV patients than in patients without CAV. The number of CD34(+)CD140b(+) cells showed a stepwise increase in patients with moderate and severe CAV. Smooth muscle progenitor cell counts were higher in patients with coronary stent implant compared with unstented patients with CAV. In contrast, peripheral CD34(+)KDR(+) EPC counts were not changed in CAV patients. Plasma CXCL12 levels correlated with the degree of CAV and SPC counts. None of the different immunosuppressive drug regimes was related to the SPC count or the CXCL12 levels. A multivariate regression analysis revealed that the SPC count was independently associated with the presence of CAV. CONCLUSION: Circulating SPCs, but not EPCs, and plasma CXCL12 concentrations are elevated in CAV patients, indicating that they play prominent roles in transplant arteriosclerosis.

Analysis of the long-term effects of drug-eluting stents on coronary arterial wall morphology as assessed by virtual histology intravascular ultrasound.

BACKGROUND: Animal models show impairment of arterial healing after drug-eluting stents (DES) compared with bare-metal stents (BMS). Virtual histology intravascular ultrasound (VH-IVUS) offers an opportunity to assess lesion morphology in vivo. METHODS: We used VH-IVUS in 80 patients to assess long-term (median = 10 months) native artery vascular responses after 76 implantations of DES compared with 32 BMS. The presence of "necrotic core abutting the lumen" was evaluated at baseline and follow-up. RESULTS: At baseline, necrotic core abutting the lumen through the stent struts was observed in 76% of DES and 75% of BMS. Although the percentage of necrotic core within the plaque behind the stents did not change during follow-up in DES (23% [18%, 28%] to 22% [17%, 27%], P = .57) or BMS (22% [19%, 27%] to 20% [12%, 26%], P = .29), necrotic core abutting the lumen through the stent struts decreased more in BMS (75% to 19%, P < .001) than DES (76% to 61%, P = .036) because of the lack of an overlying, protective neointima in DES-treated lesions. Furthermore, within the adjacent reference segments, the incidence of necrotic core abutting the lumen decreased in BMS-treated lesions (proximal 23% to 0%, P = .023; distal 21% to 0%, P = .023), but not in DES (proximal 22% to 17%, P = .48; distal 23% to 21%, P = .82). CONCLUSIONS: Serial VH-IVUS analysis of DES-treated lesions showed a greater frequency of unstable lesion morphometry at follow-up compared with BMS. The apparent mechanism was a suppression of the protective neointimal hyperplasia layer coupled with a lack of vulnerable plaque resolution at reference segments in DES compared with BMS.

Prognostic value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein as a marker for major cardiac events in asymptomatic individuals: a health technology assessment report.

OBJECTIVES: The aim of this study was to compare the predictive value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein (hs-CRP)-screening in addition to traditional risk factor screening in apparently healthy persons as a means of preventing coronary artery disease. METHODS AND RESULTS: The systematic review was performed according to internationally recognized methods. Seven studies on risk prediction, one clinical decision-analytic modeling study, and three decision-analytic cost-effectiveness studies were included. The adjusted relative risk of high hs-CRP-level ranged from 0.7 to 2.47 (p < .05 in four of seven studies). Adding hs-CRP to the prediction models increased the areas under the curve by 0.00 to 0.027. Based on the clinical decision analysis, both individuals with elevated hs-CRP-levels and those with hyperlipidemia have a similar gain in life expectancy following statin therapy. One high-quality economic modeling study suggests favorable incremental cost-effectiveness ratios for persons with elevated hs-CRP and higher risk. However, many model parameters were based on limited evidence. CONCLUSIONS: Adding hs-CRP to traditional risk factors improves risk prediction, but the clinical relevance and cost-effectiveness of this improvement remain unclear.

Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial.

BACKGROUND: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). METHODS: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26). INTERPRETATION: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. FUNDING: Biosensors Europe SA, Switzerland.

Prospective study of risk factors for conjunctival bacterial contamination in patients undergoing intraocular surgery.

PURPOSE: To determine whether a patient's age, gender, local or systemic risk factors affect the rate of preoperative bacterial contamination. METHODS: Consecutive 1,474 patients undergoing intraocular surgery were enrolled in this prospective masked study. Past medical history was noted and examinations were performed. The patients were divided into four groups: a control group (without local or systemic risk factors), those with local risk factors (chronic use of topical medications, contact lens wear, blepharitis, chronic eyelid or conjunctival inflammation), those with systemic risk factors (immunosuppression, diabetes, autoimmune conditions, and asthma), and those with both. Conjunctival cultures were obtained before surgery. RESULTS: Among the 1,474 patients, 914 bacteria were isolated from 214 (14.9%) patients. Advanced age was associated with a higher rate of positive conjunctival cultures (p<0.005). No statistical difference was found with regard to gender (p=0.7173). Among the 282 patients in the control group, 14 (5%) had a positive conjunctival culture. Compared to the control group, positive conjunctival cultures were found in 118 out of 503 patients (23.5%) with local risk factors (p<0.0001), 65 out of 545 patients (11.9%) with systemic risk factors (p=0.0019), and 22 out of 144 (15.3%) with both (p=0.0006). Two patients developed postoperative endophthalmitis (0.14%), one with both local risk and systemic factors and the other with a systemic risk factor. CONCLUSIONS: Patients with local or systemic risk factors or advanced age were found to have a higher rate of bacterial conjunctival contamination before intraocular surgery.

Effect of contrast application on interpretability and diagnostic value of dobutamine stress echocardiography in patients with intermediate coronary lesions: comparison with myocardial fractional flow reserve.

AIMS: Poor image quality remains a limitation of dobutamine stress echocardiography (DSE). This study aimed at investigating the effects of transpulmonary contrast application on endocardial border delineation and diagnostic yield of DSE in patients with intermediate coronary stenoses. The invasively measured fractional flow reserve (FFR) served as the reference standard. METHODS AND RESULTS: Seventy patients with an intermediate coronary stenosis entered the study. Cineloops were recorded during DSE before and after contrast application at rest and peak stress. Two observers blinded to angiography assessed wall motion. FFR was measured in the target vessel during repeat angiography and an FFR

A prospective randomized study to determine the efficacy of preoperative topical levofloxacin in reducing conjunctival bacterial flora.

PURPOSE: To compare the efficacy of topical levofloxacin in combination with povidone-iodine irrigation vs povidone-iodine (PVI) alone in reducing conjunctival bacteria. DESIGN: Prospective, randomized, controlled trial. METHODS: One hundred and forty eyes of 140 patients scheduled to undergo intraocular surgery eyes were randomized to either group 1 or 2 (70 each). Whereas group 1 eyes had no prophylactic antibiotic, eyes in group 2 received topical treatment with one drop of 0.5% levofloxacin four times on the day before surgery. Both groups underwent irrigation of the fornices with 1% PVI. Conjunctival swabs were inoculated on solid and broth culture media to determine bacterial growth. RESULTS: Of 132 eyes evaluated, baseline culture analysis in thioglycolate demonstrated positive culture results in 55 (84.6%) of 65 eyes from group 1, similar to 55 (82.1%) of 67 eyes in group 2 (P = .697). Before surgery, 57 (87.7%) of 65 eyes in group 1 had positive culture results, compared with 50 (74.6%) of 67 eyes in group 2 (P = .055). After irrigation with PVI, 20 (30.8 %) of 65 eyes in group 1 had positive culture results, compared with only eight (11.9%) of 67 eyes in group 2 (P = .008). After surgery, 15 (23.1%) of 65 eyes in group 1 and six (9.0%) of 67 eyes in group 2 had positive culture results (P = .027). CONCLUSIONS: Our study shows an enhanced effect of using topical levofloxacin in combination with PVI irrigation to reduce conjunctival bacteria in patients undergoing intraocular surgery.

Expression of HIF-1alpha in injured arteries controls SDF-1alpha mediated neointima formation in apolipoprotein E deficient mice.

OBJECTIVE: Hypoxia-inducible factor (HIF)-1alpha is the regulatory subunit of a transcriptional complex, which controls the recruitment of multipotent progenitor cells and tissue repair in ischemic tissue by inducing stromal cell-derived factor (SDF)-1alpha expression. Because HIF-1alpha can be activated under normoxic conditions in smooth muscle cells (SMCs) by platelet products, we investigated the role of HIF-1alpha in SDF-1alpha-mediated neointima formation after vascular injury. METHODS AND RESULTS: Wire-induced injury of the left carotid artery was performed in apolipoprotein E-deficient mice. HIF-1alpha expression was increased in the media as early as 1 day after injury, predominantly in SMCs. Nuclear translocation of HIF-1alpha and colocalization with SDF-1alpha was detected in neointimal cells after 2 weeks. HIF-1alpha mRNA expression was induced at 6 hours after injury as determined by real-time RT-PCR. Inhibition of HIF-1alpha expression by local application of HIF-1alpha-siRNA reduced the neointimal area by 49% and significantly decreased the neointimal SMCs content compared with control-siRNA. HIF-1alpha and SDF-1alpha expression were clearly diminished in neointimal cells of HIF-1alpha-siRNA treated arteries. CONCLUSIONS: HIF-1alpha expression is directly involved in neointimal formation after vascular injury and mediates the upregulation of SDF-1alpha, which may affect the stem cell-based repair of injured arteries.

Antiplatelet drugs in cardiological practice: established strategies and new developments.

A common pathophysiological course in vascular diseases is an overwhelming activation and aggregation of blood platelets, which results in atherothrombosis. By causing the last decisive step of cerebral, coronary, or peripheral arterial ischemia thrombotic complications of atherosclerotic disease represent a major player in death cause statistics of most western countries. The development of novel therapies against platelet-dependent thrombosis and the concurrent improvement of existing therapeutic strategies thus is a paramount focus of pharmaceutical research. Currently, efficiency, dosing and indications of established antiplatelet substances are being re-evaluated, whilst new, so far unrecognized molecular targets for inhibition of platelet activity come up front. This not only allows for interesting new therapeutical options, but also widens our insight into the role platelets play in atherosclerosis in general. This article summarizes the relevant pathophysiology of platelet activation, presents current concepts in antiplatelet drug therapy, and highlights the role of platelets in vascular diseases apart from atherothrombosis.