Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.

BACKGROUND: Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. METHODS: In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518. FINDINGS: Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59). INTERPRETATION: Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. FUNDING: Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

Impact of length and hydrophilic coating of the introducer sheath on radial artery spasm during transradial coronary intervention: a randomized study.

OBJECTIVES: The aim of this study was to assess the impact of length and hydrophilic coating of the introducer sheath on radial artery spasm, radial artery occlusion, and local vascular complications in patients undergoing transradial coronary procedures. BACKGROUND: Radial artery spasm is common during transradial procedures and the most common cause for procedural failure. METHODS: We randomly assigned, in a factorial design, 790 patients scheduled for a transradial coronary procedure to long (23-cm) or short (13-cm) and hydrophilic-coated or uncoated introducer sheaths. The primary outcome measure was clinical evidence of radial artery spasm, and secondary outcome measures were patient discomfort and local vascular complications. RESULTS: Procedural success was achieved in 96% of the cases, and radial artery spasm accounted for 17 of 33 failed cases. There was significantly less radial artery spasm (19.0% vs. 39.9%, odds ratio [OR]: 2.87; 95% confidence interval [CI]: 2.07 to 3.97, p < 0.001) and patient reported discomfort (15.1% vs. 28.5%, OR: 2.27; 95% CI: 1.59 to 3.23, p < 0.001) in patients receiving a hydrophilic-coated sheath. No difference was observed between long and short sheaths. Radial artery occlusion was observed in 9.5% of the patients and was not influenced by sheath length or coating. A local large hematoma or arterial dissection was seen in 2.6% of the patients with no difference in groups allocated at randomization. Younger age, female sex, diabetes, and lower body mass index were identified as independent predictors of radial artery spasm. CONCLUSIONS: Hydrophilic sheath coating, but not sheath length, reduces the incidence of radial artery spasm during transradial coronary procedures.

A randomized comparison of TR band and radistop hemostatic compression devices after transradial coronary intervention.

BACKGROUND: The transradial route for coronary intervention has proven to be safe, effective, and widely applicable in different clinical situations. Several compressive hemostatic devices have been introduced that have shown to be safe and are effective in achieving hemostasis. METHODS: Seven hundred ninety patients were randomly assigned to receive either TR band or Radistop hemostatic compression devices after transradial coronary procedure. The outcome measures were patient tolerance of the device, local vascular complications, and the time taken to achieve hemostasis. RESULTS: The mean age was 62.88 years, and 74.2% of the patients were men. Patient age, height, weight, wrist circumference, body mass index, male sex, hypertension, diabetes, hypercholesterolemia, and smoking incidences were similar in both groups. There were significantly more patients reporting no discomfort in the TR band group compared to the Radistop group (77% vs. 61%; P = 0.0001). Patients in the Radistop group reported significantly more pain across all categories of severity and three patients in the Radistop group were crossed over to TR band because of severe discomfort. Oozing and ecchymosis were seen in about 16% of the patients. Local small hematoma and large hematoma were seen in 5.4% and 2.2% patients respectively, and similar in both groups. Radial artery occlusion at the time of discharge was seen in 9.2% of the patients though only 6.8% showed persistent occlusion at the time of follow-up. The time taken to achieve hemostasis was significantly longer in the TR Band group (5.32 ± 2.29 vs. 4.83 ± 2.23 hr; P = 0.004). There was significantly higher incidence of radial artery occlusion in patients with smaller wrist circumference, the patients who experienced radial artery spasm during the procedure, and patients with no heparin administration during the procedure. CONCLUSIONS: We have shown in a randomized comparison of Radistop and TR band that both devices are safe and effective as hemostatic compression devices following transradial procedures. However, more patients felt discomfort with the Radistop device and the time taken to achieve hemostasis was longer with TR band. © 2010 Wiley-Liss, Inc.

Impact of introducer sheath coating on endothelial function in humans after transradial coronary procedures.

BACKGROUND: The aim of this study was to compare the impact of transradial catheterization with hydrophilic-coated catheter sheaths versus uncoated sheaths on NO-mediated endothelial-dependent and -independent vasodilator function. METHODS AND RESULTS: Thirty-five subjects undergoing transradial catheterization were recruited and assessed before and the day after catheterization. A subgroup was also assessed 3 to 4 months after catheterization. Subjects received hydrophilic-coated sheaths (n=15) or uncoated sheaths (n=20). Radial artery flow-mediated dilatation and endothelium- and NO-dependent arterial dilatation were assessed within the region of sheath placement. Glyceryl trinitrate endothelium-independent NO-mediated function was also assessed. The noncatheterized arm provided an internal control. Flow-mediated dilatation in the catheterized arm decreased from 10.3+/-3.8% to 5.3+/-3.3% and 8.1+/-2.4% to 5.2+/-3.7% in the coated and uncoated groups, respectively (P<0.01). These values returned toward baseline levels approximately 3 months later (coated, 6.4+/-1.4%; uncoated, 9.4+/-4.1%; P<0.05) versus postprocedure. Glyceryl trinitrate decreased from 14.8+/-7.2% to 9.5+/-4.1% (P<0.05) in the coated group and from 12.2+/-4.6% to 7.5+/-4.2% (P<0.01) in the uncoated group. Values returned to baseline at approximately 3 months (coated, 16.6+/-5.6%; uncoated, 12.1+/-3.9%; P<0.05). There was no difference in the magnitude of decrease in flow-mediated dilatation or glyceryl trinitrate between coated and uncoated groups. No changes in function occurred in the noncatheterized arm. CONCLUSIONS: Placement of a catheter sheath inside the radial artery disrupts vasodilator function, which recovers after 3 months. No differences were evident between hydrophilic-coated and uncoated sheaths.

Impact of catheter insertion using the radial approach on vasodilatation in humans.

The aim of this study was to determine the impact of catheter sheath insertion, a model of endothelium disruption in humans, on the conventional FMD (flow-mediated dilatation) response in vivo. Seventeen subjects undergoing transradial catheterization were recruited and assessed prior to, the day after, and 3-4 months postcatheterization. The catheter sheath's external diameter was 2.7 mm, and the average preprocedure internal radial artery diameter was 2.8 mm, indicating a high likelihood of endothelial denudation as a consequence of sheath placement. Radial artery flow-mediated and endothelium-derived NO (nitric oxide)-dependent function (FMD) was assessed within the region of sheath placement (sheath site) and also above the sheath (catheter site). GTN (glyceryl trinitrate) endothelium-independent NO-mediated function was also assessed distally. Measurements were made in both arms at all time points; the non-catheterized arm provided an internal control. Neither sheath (4.5+/-0.9%) nor catheter (4.4+/-0.9%) insertion abolished FMD, although both significantly decreased FMD from preintervention levels (9.0+/-0.8% sheath segment; 8.4+/-0.8% catheter segment; P<0.05). The impact of sheath and catheter placement on FMD was no longer evident after approximately 3 months recovery (8.0+/-1.5 and 8.1+/-1.7%, sheath and catheter, respectively). GTN responses also decreased from 14.8+/-1.7 to 7.9+/-1.0% (P<0.05) as a result of sheath placement, but values returned to baseline at approximately 3 months (13.0+/-1.8%). These results suggest that the presence of an intact, functional endothelial layer and consequent NO release may not be obligatory for some component of the FMD response. This raises the possibility of an endothelium-independent contribution to the flow-induced vasodilatation in humans.

The feasibility of percutaneous transradial coronary intervention for saphenous vein graft lesions and comparison with transfemoral route.

BACKGROUND: Transradial PCI is rapidly expanding and is effective in complex lesion subset due to miniaturization of devices and accumulated clinical experience. However, the femoral route still remains the usual vascular route used for SVG PCI in most catheterization laboratories. METHODS: We examined 115 consecutive patients undergoing SVG PCI between January 2003 and December 2005 and compared the radial (51 patients) and femoral (64 patients) approaches. RESULTS: Baseline demographics, lesion location, and clinical indication were similar in both groups. GpIIbIIIa inhibitor usage was high in the radial group (78.4% vs. 53.1%, P < 0.01). Angiographic success was similar in both groups, 96% in the radial group vs. 96.8 in the femoral. Total fluoroscopy time (18.59 +/- 12.23 vs. 20.45 +/- 12.9), total procedure time (52.1 +/- 29.5 vs. 43.90 +/- 23.31 min), and the use of total contrast volume (357.0 +/- 174.0 vs. 346.0 +/- 157.0 ml) were similar in the radial and femoral groups, respectively. In-hospital MACE (radial: 2 MI [4.0%] vs. femoral: 1 death [1.6%] and 7 MI [11.0%], P < 0.01) were similar in both groups. Access site vascular complications (radial: 2 [4.0%] vs. femoral: 10 [11.0%], P < 0.001) were significantly less in the radial group. CONCLUSIONS: The transradial approach for SVG PCI is feasible, safe, and as quick as the femoral approach. Procedural success is high with similar radiation and contrast exposure. In-hospital MI in the femoral group is high because of more-unstable patients. However, there are significantly lower vascular complications despite high use of platelet inhibitors in the radial approach.

Thrombus extrusion through filter wire basket.

A 56-year old male presenting with acute coronary syndrome was found to have a large thrombus partially including a bypass graft bare metal stent. This thrombus was removed using a filter wire. The thrombus burden was so large that it caused extension through the filter wire basket, narrowly avoiding distal embolisation.

A comparison of the transradial and the transfemoral approach in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Transradial coronary intervention is a safe and effective method of percutaneous revascularization. Furthermore, the indications for transradial percutaneous coronary intervention (PCI) are expanding. However, there is limited data on the efficacy and the safety of the transradial approach for chronic total occlusion (CTO) PCI. METHODS: We examined 468 patients who underwent CTO PCI between January 2003 and December 2005, and compared the radial (318 patients) and the femoral (150 patients) approach. RESULTS: Baseline demographics, lesion location, and the vessel treated were similar in both groups. Angiographic success was 82% in radial versus 86% in femoral group, P = 0.28, similar in both groups. Total fluoroscopy time (24.49 +/- 13.18 vs. 24.07 +/- 14.12 min, P = 0.36), total procedure time (54.22 +/- 25.35 vs. 60.23 +/- 28.15 min, P = 0.23), and the use of total contrast volume (395.54 +/- 180.25 vs. 406.15 +/- 173.98 ml, P = 0.27) were similar in radial and femoral group, respectively. In hospital MACE [radial: 12 MI (3.8%) vs. femoral: 1 death (0.7%) and 5 MI (3.5%), P = 0.26] were similar in both groups. Access site vascular complications [radial: 11 (3.5%) vs. femoral: 17 (11.3%), P

The radial approach: is this the route to take?

The benefits of the transradial approach have clearly been demonstrated over the years in various studies. The reduced incidence of access site complications and early mobilization are some of the benefits making this technique popular with interventional cardiologists worldwide. With increasing experience and availability of dedicated equipment this technique is now been increasingly used for complex catheter interventions. However, there still remain some potential problems and complications with the transradial approach and it needs further research. The main purpose of this review is to highlight the benefits, complications, and potential problems with the transradial approach.

Postdilatation following coronary stent deployment: lesion and procedural characteristics associated with an increase in stent dimensions.

UNLABELLED: Adjunctive balloon postdilatation following stent deployment is often used to optimize stent expansion. However, the benefit of this strategy with modern stent delivery systems is not known. We investigated angiographic and procedural factors associated with a favorable response to postdilatation after coronary stent deployment. METHODS: We performed a prospective study recruiting 385 patients (490 lesions) who underwent stent deployment. Quantitative coronary angiography was used to measure the minimal lumen diameter (MLD) within the stent before and after postdilatation. Optimal stent deployment was defined as a stent MLD greater than or equal to 90% of the reference vessel diameter. RESULTS: Postdilatation was performed in 41.2% (202/490) of cases, with an increase in stent MLD from mean (SD) 2.50 (0.40) to 2.70 (0.38) mm, p < 0.0001. Optimal stent deployment increased from 35.6% (72/202) to 56.5% (115/202). The percentage increase in stent MLD with postdilatation was greatest in cases with a residual stenosis of > 20% after coronary stenting or a stent deployment pressure < or = 14 atm. Vessel size and predilatation had no impact on the response to postdilatation. In those cases where postdilatation was not performed, optimal stent deployment was achieved in 64.9% (187/288) of cases. CONCLUSION: A significant proportion of patients did not achieve optimal stent deployment with modern stent delivery systems. The increase in stent MLD with postdilatation was greater in cases with lower stent deployment pressures and more significant residual stenoses.

Stent expansion: a combination of delivery balloon underexpansion and acute stent recoil reduces predicted stent diameter irrespective of reference vessel size.

BACKGROUND: There is a strong inverse relationship between final vessel diameter and subsequent risk of treatment failure after coronary stent deployment. The aim of this study was to investigate the magnitude by which stent delivery balloon underexpansion and stent elastic recoil contributed to suboptimal final vessel geometry. METHODS: A prospective angiographic study recruiting 499 lesions (385 patients) undergoing coronary stent implantation was performed. Quantitative coronary angiography (QCA) was used to measure the minimal lumen diameters of the delivery balloon during stent deployment (MLD1) and of the stented segment following balloon deflation (MLD2). The expected balloon diameter for the deployment pressure was determined from the manufacturer's reference chart. Delivery balloon deficit was measured by subtracting the MLD1 from the expected balloon size and stent recoil was calculated by subtracting MLD2 from MLD1. Delivery balloon deficit and stent recoil were examined as a function of reference vessel diameter (RVD) and balloon-vessel (BV) ratio. RESULTS: The final stent MLD was a mean 27.2% (SD = 7.2) less than the predicted diameter. The mean delivery balloon deficit was 0.65 mm (SD = 0.27) and the mean stent recoil was 0.28 mm (SD = 0.17). Percentage delivery balloon deficit and stent recoil were independent of RVD. Delivery balloon deficit increased with higher BV ratios. Stent recoil was independent of BV ratio and the use of predilatation. CONCLUSION: Failure to achieve predicted final stent diameter is a real problem with contribution from delivery balloon underexpansion and stent recoil. On average the final stent MLD is only 73% of the expected diameter, irrespective of vessel size.

Late stent thrombosis associated with coronary aneurysm formation after sirolimus-eluting stent implantation.

Stent thrombosis is a rare but potentially fatal complication of coronary stent implantation. Its occurrence late after drug-eluting stent (DES) deployment has led to concerns regarding their long-term safety. We report a case of late stent thrombosis 26 months after sirolimus-eluting stent (SES) (Cypher, Cordis Corp., Miami, Florida) implantation. This was associated with marked positive vessel remodeling and coronary aneurysm formation involving the stented segment of the coronary artery. The patient was on dual antiplatelet therapy at the time.

A study comparing the incidence and predictors of creatine kinase MB and troponin T release after coronary angioplasty. Does Clopidogrel preloading reduce myocardial necrosis following elective percutaneous coronary intervention?

BACKGROUND: To investigate the incidence and associated factors for enzyme release following percutaneous coronary intervention comparing assessment with creatine kinase MB (CK-MB) and troponin T (TnT). METHOD: TnT and CK-MB were measured post procedure in a consecutive series of 933 patients undergoing elective percutaneous coronary intervention between 1/4/2003 and 1/5/2004 at a single regional cardiac centre. RESULTS: CK-MB level significantly correlated to TnT levels (R=0.747, p<0.001) and a CK-MB level of above 3 times the upper limit of the local reference range (>3 x ULN) was predicted with 95% sensitivity (48% specificity) at a TnT level of 0.11. Multivariate predictors of >3 x ULN CK-MB release for uncomplicated percutaneous coronary intervention (n=898) were multi-vessel angioplasty (OR=2.51, 95% CI=1.57 to 4.01; p<0.001), saphenous venous graft angioplasty (OR=5.5, 95% CI=1.94 to 13.00; p=0.005) and lack of Clopidogrel preloading (OR=2.02, 95% CI=1.30 to 4.38; p=0.027). CONCLUSIONS: TnT was found to be a sensitive although not a highly specific marker of CK-MB release. In this study a TnT level above a threshold of 0.11 would identify 95% of the prognostically important 3-fold CK-MB releases. Replacing the >3 x ULN CK-MB threshold with a TnT level of 0.1 ng/l following percutaneous coronary intervention would increase the apparent rate of myocardial infarction from 11% to 20%. Lack of Clopidogrel preloading was independently associated with a >3 x ULN CK-MB release following uncomplicated elective percutaneous coronary intervention.

Transradial treatment of bifurcation coronary disease using the Multi-Link Frontier bifurcation stent system.

Percutaneous coronary intervention (PCI) for bifurcation lesions is technically limited by the risk of side branch occlusion. Despite using various strategies for the treatment of bifurcation lesions, adequate stent coverage of the side branch ostium remains difficult with conventional stent design. The Multi-Link Frontier stent is a specifically designed bifurcation stent that allows stenting of the main branch and the side branch ostium with a single stent, whilst preserving access to the side branch. Requirement for a 7 French (Fr) guide has discouraged operators from using this device via a transradial approach. We present the immediate results of using the Multi-Link Frontier stent in 5 consecutive cases with bifurcation coronary lesions using a transradial approach.

Nonsteroidal anti-inflammatory agents in neonates.

The use of NSAIDs has become routine for adults and children in the management of pain. NSAIDs (other than aspirin [acetylsalicylic acid]) are also enjoying greater popularity as antipyretics since the recognition of Reye's syndrome's putative association with aspirin. In neonates, NSAIDs have been used for many years in an attempt to pharmacologically close the ductus arteriosus. This review examines the various NSAIDs and their potential and real applications in the neonatal population. For completeness, acetaminophen (paracetamol), which has weak NSAID activity and is a widely used analgesic and antipyretic in this patient group, was also included. The prostaglandin system is important for healthy development, and conversely there are unique risks posed by pharmacologic interference with this system in the neonatal period. The prostanoid system in neonates has the capacity to modulate nociception, but comes at the expense of interfering with nearly every organ system. Physiologic effects of inhibition of prostaglandin synthesis applicable to neonates include disruption of the sleep cycle, increased risk of pulmonary hypertension, alterations in cerebral blood flow, decreased renal function, disrupted thermoregulation, and alterations in hemostasis balance, among others. Prostaglandins are also important for the normal development of the central nervous, cardiovascular, and renal systems, and there is evidence that the proper genesis of these systems may be adversely effected by NSAID exposure in utero and in the neonatal period. Gastrointestinal adverse effects have provided the impetus for the development and marketing of selective cyclo-oxygenase type 2 (COX-2) inhibitors. These agents' reputation for safety in adults may not be applicable to neonates. COX-2 is involved in the development of several organ systems, and its inhibition may induce a prothrombotic state. The advent of parenteral formulations of cyclo-oxygenase inhibitors, including COX-2-selective agents, increases the therapeutic flexibility of NSAIDs. However, objective data on the safety of these agents have not kept pace with their clinical availability.

Extracorporeal CO2 removal in a child with a single ventricle by the addition of an oxygenator to a dialysis circuit.

OBJECTIVE: To optimize CO2 removal in a child with a single ventricle. DESIGN: Case report. SETTING: A ten-bed pediatric intensive care unit in a university-affiliated hospital. PATIENT: A 6-yr-old boy with a single ventricle who underwent a Fontan procedure. INTERVENTIONS: Addition of a membrane oxygenator to a venovenous hemodialysis circuit. MEASUREMENTS: Patient respiratory variables were measured. MAIN RESULTS: A clinically significant improvement in CO2 removal was achieved. CONCLUSIONS: Addition of a membrane oxygenator to a dialysis circuit facilitates CO2 removal.