Thrombus aspiration and prehospital ticagrelor administration in ST-elevation myocardial infarction: Findings from the ATLANTIC trial.

BACKGROUND: The potential interactions between prehospital (pre-H) ticagrelor administration and thrombus aspiration (TA) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) have never been studied. Therefore, we evaluated the potential benefit of TA and pre-H ticagrelor treatment in patients enrolled in the ATLANTIC trial (NCT01347580). METHODS: This analysis included 1,630 patients who underwent primary PCI. Multivariate analysis was used to explore the potential association of TA and pre-H treatment to clinical outcomes. Potential interactions between TA and pre-H ticagrelor were also explored. RESULTS: A total of 941 (57.7%) patients underwent TA. In adjusted multivariate logistic model, pre-H ticagrelor treatment was significantly associated with less frequent new MI or definite stent *thrombosis (ST) (odds ratio [OR] 0.43, 95% CI 0.20-0.92, P=.031), or definite ST (OR 0.26, 95% CI 0.07-0.91, P=.036) at 30 days. Patients treated with TA had higher frequency of Thrombolysis in Myocardial Infarction (TIMI) flow 0-1 compared with no-TA group (80.7% vs 51.9%, P<.0001). TA when also adjusted for TIMI flow 0-1 showed significant association only for higher bailout use of glycoprotein IIb/IIIa inhibitors (OR 1.72, 95% CI 1.18-2.50, P=.004) and more frequent 30-day TIMI major bleeding (OR 2.92, 95% CI 1.10-7.76, P=.032). No significant interactions between TA and pre-H ticagrelor were present for the explored end points. CONCLUSIONS: TA when left to physicians' discretion was used in high-risk patients, was associated with bailout use of glycoprotein IIb/IIIa inhibitors and TIMI major bleeding, and had no impact on 30-day clinical outcomes. Conversely, pre-H ticagrelor treatment predicted lower 30-day rates of ST or new MI without interaction with TA.

Arterial-cardiac baroreflex function: insights from repeated squat-stand maneuvers.

To assess baroreflex function under closed-loop conditions, a new approach was used to generate large and physiological perturbations in arterial pressure. Blood pressure (BP) and R-R interval were recorded continuously in 20 healthy young (33 +/- 8 yr) and eight elderly subjects (66 +/- 6 yr). Repeated squat-stand maneuvers at the frequencies of 0.05 and 0.1 Hz were performed to produce periodic oscillations in BP to provoke the baroreflex. To assess the effects of the muscle reflex and/or central command on the baroreflex, passive squat-stand maneuvers were conducted using a pulley system to assist changes in body position. Transfer function between changes in BP and R-R interval was estimated to assess the arterial-cardiac baroreflex. Relative to resting conditions, large and coherent oscillations in BP and R-R interval were produced during both active and passive squat-stand maneuvers. However, changes in BP were smaller during passive than during active maneuvers. Changes in R-R interval were reduced commensurately. Therefore, transfer function gain did not change between the two maneuvers. Compared with the young, transfer function gain was reduced and the phase became more negative in the elderly, demonstrating the well-known effects of aging on reducing baroreflex sensitivity. Collectively, these findings suggest that the changes in R-R interval elicited by BP perturbations during squat-stand maneuvers are mediated primarily by a baroreflex mechanism. Furthermore, baroreflex function can be assessed using the transfer function method during large perturbations in arterial pressure.

A fugacity based continuous and dynamic fate and transport model for river networks and its application to Altamaha River.

In this paper, a continuous and dynamic fugacity-based contaminant fate and transport model is developed. The dynamic interactions among all phases in the physical domain are addressed through the use of the fugacity approach instead of the use of concentration as the unknown variable. The full form of Saint Venant equations is used in order to solve for the hydrodynamic conditions in the river network. Then a fugacity-based advection-dispersion equation is modeled to examine the fate and transport of contaminants in the river network for all phases. The fugacity-based, dynamic and continuous contaminant fate and transport model developed here is applied to Altamaha River in Georgia, USA to demonstrate its use in environmental exposure analysis. Altamaha River is the largest river system east of Mississippi which offers habitat for many species, including about 100 rare endangered species, along its 140 mile course. Polychlorinated biphenyls (PCBs), a highly hydrophobic and toxic chemical ubiquitous in nature, and atrazine, the most commonly-used agricultural pesticide are modeled as contaminants in this demonstration. Through this approach the concentration distribution of PCBs and atrazine in the water column of Altamaha River as well as the sediments can be obtained with relative ease, which is an improvement over concentration based analysis of phase distribution of contaminants.

One-Year Mortality for Bivalirudin vs Heparins Plus Optional Glycoprotein IIb/IIIa Inhibitor Treatment Started in the Ambulance for ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of the EUROMAX Randomized Clinical Trial.

Importance: Uncertainty exists regarding potential survival benefits of bivalirudin compared with heparin with routine or optional use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-segment elevation myocardial infarction (STEMI). Few data are available regarding long-term mortality in the context of contemporary practice with frequent use of radial access and novel platelet adenosine diphosphate P2Y12 receptor inhibitors. Objective: To assess the effect of bivalirudin monotherapy compared with unfractionated or low-molecular-weight heparin plus optional GPIs on 1-year mortality. Design, Setting, and Participants: This international, randomized, open-label clinical trial (EUROMAX [European Ambulance Acute Coronary Syndrome Angiography]) included 2198 patients with STEMI undergoing transport for primary percutaneous coronary intervention from March 10, 2010, through June 20, 2013, and followed up for 1 year. Patients were randomized (1:1) in ambulance to bivalirudin monotherapy vs unfractionated or low-molecular-weight heparin plus optional GPIs (control group). Analysis was based on intention to treat. Main Outcomes and Measures: The primary outcome of this prespecified analysis was 1-year mortality. All deaths were adjudicated as cardiac or noncardiac by an independent, blinded clinical events committee. One-year mortality was assessed and examined across multiple prespecified subgroups. Results: Of the 2198 patients enrolled (1675 men [76.2%] and 523 women [23.8%]; median [interquartile range] age, 62 [52-72] years), complete 1-year follow-up data were available for 2164 (98.5%). All-cause 1-year mortality occurred in 118 patients (5.4%). The number of all-cause deaths was the same for both treatment groups (59 deaths; relative risk [RR], 1.02; 95% CI, 0.72-1.45; P = .92). No differences were noted in the rates of 1-year cardiac death (44 [4.0%] for the bivalirudin group vs 48 [4.3%] for the control group; RR, 0.93; 95% CI, 0.63-1.39; P = .74) or noncardiac death (15 [1.4%] for the bivalirudin group vs 11 [1.0%] for the control group; RR, 1.39; 95% CI, 0.64-3.01; P = .40). Results were consistent across the prespecified patient subgroups. The rate of deaths occurring from 30 days to 1 year was also similar (27 [2.5%] in the bivalirudin group vs 25 [2.3%] in the control group; RR, 1.10; 95% CI, 0.64-1.88; P = .73). Conclusions and Relevance: In patients with STEMI who were being transported for primary percutaneous coronary intervention, treatment with bivalirudin or with heparin with optional use of GPI resulted in similar 1-year mortality. The reduced composite end point of death and/or major bleeding at 30 days in the bivalirudin arm of the EUROMAX trial did not translate into reduced cardiovascular or all-cause death at 1 year. Trial Registration: clinicaltrials.gov Identifier: NCT01087723.

Long-term mortality and prehospital tirofiban treatment in patients with ST elevation myocardial infarction.

OBJECTIVE: We undertook a subgroup analysis of the On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2), a placebo-controlled, double-blind, randomised trial, in order to evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and long-term (5 years) mortality and to investigate the effect of prehospital tirofiban administration on mortality in relation to NT-proBNP levels. METHODS: A total of 984 patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) were randomised to either in ambulance tirofiban or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18-96 hours thereafter (post PCI). RESULTS: There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post PCI. Patients with baseline NT-proBNP values above the median (137 pg/mL) had higher 30-day (5.1% vs 0.2%, p<0.001), 1-year (7.0% vs 0.7%, p<0.001) and 5-year (20.3% vs 4.9%, p<0.001) mortality as compared with patients with values below the median. Using multivariate Cox analysis, NT-proBNP above the median was an independent predictor for 5-year mortality (HR 2.73, 95% CI 1.47 to 5.06; p=0.002). Patients with values above the median who received early tirofiban treatment had significant lower mortality compared with patients treated with placebo at 30 days (2.7% vs 7.5%, p=0.021) and 1 year (4.5% vs 9.4%, p=0.043). At 5 years, a lower but non-significant mortality rate was maintained in the treatment group (18% vs 22.4%, p=0.265). CONCLUSIONS: In patients with STEMI, baseline NT-proBNP level independently predicts long-term mortality. In patients with baseline NT-proBNP levels above the median, early prehospital treatment with tirofiban significantly reduced 30-day and 1-year mortality, suggesting that high-risk patients may derive particular benefit. This finding should be confirmed in other studies. TRIAL REGISTRATION NUMBER: ISRCTN06195297.

Frequency and prognostic significance of access site and non-access site bleeding and impact of choice of antithrombin therapy in patients undergoing primary percutaneous coronary intervention. The EUROMAX trial.

BACKGROUND: The overall impact of post percutaneous coronary intervention (PCI) bleeding on long term prognosis after acute coronary syndromes (ACS) has been established, but it may differ between access and non-access related bleeding events. The impact of antithrombin choice on bleeding may also differ according to the origin of the bleed. We sought to determine the origin of bleeding relative to the access site, its prognostic significance and the respective impact of antithrombin therapy in the EUROMAX trial. METHODS: We performed a blinded review of the case records of all TIMI major or minor bleeds in the EUROMAX trial and assigned them in one of 2 categories: access site bleeds (ASB), or rest of bleeds (ROB). Incidence of bleeding for each category was assessed according to randomization to antithrombotic treatment. RESULTS: A total of 231 out of 2198 patients suffered a TIMI major/minor bleed (10.5%) and ASB accounted for 48.5%, while ROB for 51.5% of the bleeds. Thirty day mortality was 2.5% (50/1967) for patients without a bleed, 2.7% (3/112, p=0.76 vs. no bleed) for patients with ASB, and 10.9% (13/119, p<0.0001 vs. no bleed) for ROB patients. The use of bivalirudin reduced both ASB and ROB with relative risk reductions of 34% and 46% respectively. CONCLUSIONS: In contemporary primary PCI, bleeding originates with equal frequency either at or away from the access site. Access site bleeds were not associated with an excess in 30day mortality, but the rest of the bleeds were. Bivalirudin is associated with a lower risk of bleeding irrespective of origin. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01087723.

The effect of thrombus aspiration during primary percutaneous coronary intervention on clinical outcome in daily clinical practice.

It was the purpose of this study to assess the effect of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) on reperfusion and clinical outcome in a real-world STEMI population. The decision to use TA (Export catheter, Medtronic) was at the discretion of the treating cardiologist. The primary endpoint was mortality at short (in-hospital) and long term (one year) follow-up. Secondary end points were post-PCI TIMI flow, residual ST deviation and enzymatic infarct size. Cox proportional hazard models (propensity-weighted) and logistic regression analysis were used to adjust for known covariates, associated with mortality. We performed a retrospective analysis of prospectively collected data on 2,552 consecutive PPCI-treated STEMI patients between 2007 and 2010. Use of TA increased from 6.9% in 2007 to 62.2% in 2010 (p<0.001). TA was performed in 899 patients (35.2%). In-hospital and one-year mortality rates were 3.0% and 6.0%, respectively, in the TA group and 3.5% and 7.6% in the no-TA group. After multivariate analysis, TA was not significantly associated with in-hospital mortality (adjusted odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.33-1.49, p=0.36) nor one year mortality (adjusted hazard ratio [HR]: 0.75, 95%CI: 0.47-1.20, p=0.23) or cardiac mortality (HR: 0.81; 95%CI: 0.45-1.46, p=0.49). After matching on the propensity score, the HR in the TA group for one year mortality was 0.70 (95%CI: 0.41-1.20, p=0.19) and for one-year cardiac mortality 0.70 (95%CI: 0.36-1.34, p=0.28). In conclusion, no significant relationship of TA with one of the secondary end points was found. The use of TA increased over the last years but clinical outcome was similar in both groups (TA vs no-TA) in this large cohort of real-world, unselected STEMI patients.

Probabilistic fugacity analysis of Lake Pontchartrain pollution after Hurricane Katrina.

After Hurricane Katrina passed through the US Gulf Coast in August 2005, floodwaters covering New Orleans were pumped into Lake Pontchartrain as part of the rehabilitation process in order to make the city habitable again. The long-term consequences of this environmentally critical decision were difficult to assess at the time and were left to observation. In the aftermath of these natural disasters, and in cases of emergency, the proactive use of screening level models may prove to be an important factor in making appropriate decisions to identify cost effective and environmentally friendly mitigation solutions. In this paper, we propose such a model and demonstrate its use through the application of several hypothetical scenarios to examine the likely response of Lake Pontchartrain to the contaminant loading that were possibly in the New Orleans floodwaters. For this purpose, an unsteady-state fugacity model was developed in order to examine the environmental effects of contaminants with different physicochemical characteristics on Lake Pontchartrain. The three representative contaminants selected for this purpose are benzene, atrazine, and polychlorinated biphenyls (PCBs). The proposed approach yields continuous fugacity values for contaminants in the water, air, and sediment compartments of the lake system which are analogous to concentrations. Since contaminant data for the floodwaters are limited, an uncertainty analysis was also performed in this study. The effects of uncertainty in the model parameters were investigated through Monte Carlo analysis. Results indicate that the acceptable recovery of Lake Pontchartrain will require a long period of time. The computed time range for the levels of the three contaminants considered in this study to decrease to maximum contaminant levels (MCLs) is about 1 year to 68 years. The model can be implemented to assess the possible extent of damage inflicted by any storm event on the natural water resources of Southern Louisiana or similar environments elsewhere. Furthermore, the model developed can be used as a useful decision-making tool for planning and remediation in similar emergency situations by examining various potential contamination scenarios and their consequences.