High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration: isrctn.com Identifier: ISRCTN57819173.

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).

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.

Nonculprit Lesion Severity and Outcome of Revascularization in Patients With STEMI and Multivessel Coronary Disease.

BACKGROUND: In the COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial, angiography-guided percutaneous coronary intervention (PCI) of nonculprit lesions with the aim of complete revascularization reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (MI) and multivessel coronary artery disease. OBJECTIVES: The purpose of this study was to determine the effect of nonculprit-lesion stenosis severity measured by quantitative coronary angiography (QCA) on the benefit of complete revascularization. METHODS: Among 4,041 patients randomized in the COMPLETE trial, nonculprit lesion stenosis severity was measured using QCA in the angiographic core laboratory in 3,851 patients with 5,355 nonculprit lesions. In pre-specified analyses, the treatment effect in patients with QCA stenosis ≥60% versus <60% on the first coprimary outcome of CV death or new MI and the second co-primary outcome of CV death, new MI, or ischemia-driven revascularization was determined. RESULTS: The first coprimary outcome was reduced with complete revascularization in the 2,479 patients with QCA stenosis ≥60% (2.5%/year vs. 4.2%/year; hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47 to 0.79), but not in the 1,372 patients with QCA stenosis <60% (3.0%/year vs. 2.9%/year; HR: 1.04; 95% CI: 0.72 to 1.50; interaction p = 0.02). The second coprimary outcome was reduced in patients with QCA stenosis ≥60% (2.9%/year vs. 6.9%/year; HR: 0.43; 95% CI: 0.34 to 0.54) to a greater extent than patients with QCA stenosis <60% (3.3%/year vs. 5.2%/year; HR: 0.65; 95% CI: 0.47 to 0.89; interaction p = 0.04). CONCLUSIONS: Among patients with ST-segment elevation MI and multivessel coronary artery disease, complete revascularization reduced major CV outcomes to a greater extent in patients with stenosis severity of ≥60% compared with <60%, as determined by quantitative coronary angiography.

Altered fibrin clot structure in the healthy relatives of patients with premature coronary artery disease.

BACKGROUND: A family history of premature coronary artery disease (CAD) is an independent cardiovascular risk factor. Fibrin clots composed of dense fiber networks are found in young CAD patients and may occur in the relatives of such individuals. METHODS AND RESULTS: The ex vivo fibrin structure of 100 healthy male relatives of patients with premature CAD and 100 age-matched control subjects was assessed by measurement of permeability (K(s)), fiber mass-length ratio ( micro ), and turbidity (lag phase and maximum absorbency [max DeltaAbs]). Scanning electron microscopy was performed on selected samples. Relatives and controls shared similar levels of conventional cardiovascular risk factors. K(s) was lower in relatives than in controls, 12.2 (11.1 to 13.3) versus 15.2 (14.0 to 16.5) x10(-9) cm(2) (P<0.001), associated with a smaller decrease in micro, 8.5 (7.7 to 9.2) versus 9.7 (8.9 to 10.5) x 10(13) Da/cm (P<0.05), respectively. Lag phase was shorter in relatives than in controls, 39 (37 to 41) versus 47 (44 to 50) seconds (P<0.001), and max DeltaAbs was higher in relatives, 0.78 (0.74 to 0.82) versus 0.71 (0.67 to 0.74) in controls (P=0.02), which indicates the presence of thicker fibers in relatives. After adjustment for fibrinogen levels, lag phase and K(s) remained significantly different between relatives and control subjects. Scanning electron microscopy images confirmed increased fiber diameter in relatives, possibly of reduced density. Factor XIII Val34Leu and fibrinogen Aalpha Thr312Ala and Bbeta -455 G/A showed no association with clot structure. CONCLUSIONS: The male relatives of patients with premature CAD form fibrin clots that begin polymerization more quickly, have thicker fibers, and are less permeable than those of control subjects.

Tissue plasminogen activator, fibrin D-dimer, and insulin resistance in the relatives of patients with premature coronary artery disease.

Elevated levels of tissue-type plasminogen activator antigen (tPA), fibrinogen, and fibrin D-dimer predict coronary artery disease (CAD) events and stroke. These factors, possibly in association with insulin resistance, may be important in families in which CAD has become clinically apparent at a premature age. From 125 patients with angiographically confirmed, premature CAD, 175 healthy male relatives (age

Evading the fate of Pheidippides: acute coronary thrombosis in a young marathon runner with minimal atherosclerosis but sickle cell trait.

Marathon running transiently increases the risk of sudden cardiac death. Some previous studies have suggested that this is due to relatively advanced but asymptomatic atherosclerosis. Other theories suggest that potentiation of inflammation and the coagulation cascade, by extremes of exertion, is more important. We present a clinical case of a young, previously fit athlete who felt chest discomfort eight miles into a marathon but finished the race. Shortly after completion he felt very unwell and had chest pain. Ambulance electrocardiograms showed evidence of an evolving anterior myocardial infarction. Invasive assessment with coronary angiography and intravascular ultrasound was able to show the mechanism of thrombosis. Fissuring of a small rim of atherosclerosis potentiated a large pro-thrombotic response, the patient was also found to have sickle cell trait. Medical treatment with blood thinning drugs was able to restore normality to the vessel over a period of two weeks, without the need for angioplasty or stent implantation.

Primary Care Atrial Fibrillation Service: outcomes from consultant-led anticoagulation assessment clinics in the primary care setting in the UK.

OBJECTIVE: Stroke-risk in atrial fibrillation (AF) can be significantly reduced by appropriate thromboembolic prophylaxis. However, National Institute for Health and Care Excellence estimates suggest that up to half of eligible patients with AF are not anticoagulated, with severe consequences for stroke prevention. We aimed to determine the outcome of an innovative Primary Care AF (PCAF) service on anticoagulation uptake in a cohort of high-risk patients with AF in the UK. METHODS: The PCAF service is a novel cooperative pathway providing specialist resources within general practitioner (GP) practices. It utilises a four-phase protocol to identify high-risk patients with AF (CHA2DS2-VASc ≥ 1) who are suboptimally anticoagulated, and delivers Consultant-led anticoagulation assessment within the local GP practice. We assessed rates of anticoagulation in high-risk patients before and after PCAF service intervention, and determined compliance with newly-initiated anticoagulation at follow-up. RESULTS: The PCAF service was delivered in 56 GP practices (population 386,624; AF prevalence 2.1%) between June 2012 and June 2014. 1579 high-risk patients with AF with suboptimal anticoagulation (either not taking any anticoagulation or taking warfarin but with a low time-in-therapeutic-range) were invited for review, with 86% attending. Of 1063 eligible patients on no anticoagulation, 1020 (96%) agreed to start warfarin (459 (43%)) or a non-vitamin K antagonist oral anticoagulant (NOAC, 561 (53%)). The overall proportion of eligible patients receiving anticoagulation improved from 77% to 95% (p<0.0001). Additionally, 111/121 (92%) patients suboptimally treated with warfarin agreed to switch to a NOAC. Audit of eight practices after 195 (185-606) days showed that 90% of patients started on a new anticoagulant therapy had continued treatment. Based on data extrapolated from previous studies, around 30-35 strokes per year may have been prevented in these previously under-treated high-risk patients. CONCLUSIONS: Systematic identification of patients with AF with high stroke-risk and consultation in PCAF consultant-led clinics effectively delivers oral anticoagulation to high-risk patients with AF in the community.

Factor XIII-circulating levels and the Val34Leu polymorphism in the healthy male relatives of patients with severe coronary artery disease.

We aimed to investigate whether increased levels of FXIII and/or a low prevalence of the protective Leu allele (of the Val34Leu FXIII polymorphism) occur in relatives of patients with severe CAD. 185 healthy male relatives aged 65 or less were recruited from 125 patients with multi-vessel CAD and compared to 185 healthy, age-matched controls. The relatives and controls were similar in terms of clinical parameters. FXIII B-subunit levels were elevated in relatives, 1.11 microg/mL (1.08-1.14), compared with controls, 1.00 microg/mL (0.97-1.04), P <0.0001 but FXIII A2B2 levels did not differ between the groups. There was a strong correlation between FXIII B-subunit and the insulin resistance syndrome, however, adjusted B-subunit levels remained significantly higher in relatives. There was no difference in genotype frequency at the FXIII Val34Leu polymorphism between relatives and controls. FXIII B-subunit levels are elevated in the relatives of CAD patients and this is independent of other cardiovascular risk factors.

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.