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Objective: First-phase ejection fraction (EF1) is a novel measure of early left ventricular systolic dysfunction. We investigated determinants of EF1 and its prognostic value in aortic stenosis., Methods: EF1 was measured retrospectively in participants of an echocardiography/cardiovascular magnetic resonance cohort study which recruited patients with aortic stenosis (peak aortic velocity of ≥2 m/s) between 2012 and 2014. Linear regression models were constructed to examine variables associated with EF1. Cox proportional hazards were used to determine the prognostic power of EF1 for aortic valve replacement (AVR, performed as part of clinical care in accordance with international guidelines) or death., Results: Total follow-up of the 149 participants (69.8% male, 70 (65-76) years, mean gradient 33 (21-42) mm Hg) was 238 029 person-days. Sixty-seven participants (45%) had a low baseline EF1 (<25%) despite normal ejection fraction (67% (62%-71%)). Patients with low EF1 had more severe aortic stenosis (mean gradient 39 (34-45) mm Hg vs 24 (16-35) mm Hg, p<0.001) and more myocardial fibrosis (indexed extracellular volume (iECV) (24.2 (19.6-28.7) mL/m 2 vs 20.6 (16.8-24.3) mL/m 2 , p=0.002; late gadolinium enhancement (LGE) prevalence 52% vs 20%, p<0.001). Zva, iECV and infarct LGE were independent predictors of EF1. EF1 improved post-AVR (n=57 with post-AVR EF1 available, baseline 16 (12-24) vs follow-up 27% (22%-31%); p<0.001). Low baseline EF1 was an independent predictor of AVR/death (HR 5.6, 95% CI 3.4 to 9.4), driven by AVR., Conclusion: EF1 quantifies early, potentially reversible systolic dysfunction in aortic stenosis, is associated with global afterload and myocardial fibrosis, and is an independent predictor of AVR., Competing Interests: Competing interests: HG and PC are named on a patent for the use of first-phase ejection fraction (WO2017144851A1)., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

CLINICAL INTRODUCTION: A retired 59-year-old woman presented to the cardiology clinic concerned with cardiac pulsations that were visible on her chest wall. These were not associated with dyspnoea, syncope or chest discomfort.Of note, 8 years previously, she complained of recurrent nocturnal diaphoresis and 5 kg weight loss. Blood sampling at that time revealed a microcytic anaemia, reactive thrombocytosis and raised inflammatory markers (erythrocyte sedimentation rate 99 mm/hour, C-reactive protein 161 mg/L). Following an episode of transient diplopia, ophthalmoscopy demonstrated a cotton wool spot in the left inferotemporal retinal arcade. She commenced a 2-year tapering course of 1 mg/kg prednisolone.On examination, she had a lean physique with a supine blood pressure of 162/60 mm Hg and palpable Corrigan's pulse. She had a prominent apical pulsation and a loud early diastolic murmur was present at the left sternal edge radiating to the apex. Echocardiography showed severe central aortic regurgitation and a dilated aortic root (see online supplementary figure 1). Cardiac CT was performed to clarify the diagnosis (figure 1).DC1SP110.1136/heartjnl-2017-312193.supp1Supplementary file 1 heartjnl;104/3/273/F1F1F1Figure 1Contrast-enhanced CT of the thorax at index presentation (A) and 6 months (B). Prospective ECG-gated cardiac CT angiogram (75% R-R interval) performed at 8 years from index presentation (C) with a stretched multiplanar reconstruction of the aortic annulus, aortic root and thoracic aorta (D)., Question: Which of the following diagnoses best explains this presentation?Ankylosing spondylitisTakayasu arteritisSalmonellosisIgG4-related aortitisGiant cell aortitis., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Atrial fibrillation increases stroke risk and adversely affects cardiovascular haemodynamics. Electrical cardioversion may, by restoring sinus rhythm, improve cardiovascular haemodynamics, reduce the risk of stroke, and obviate the need for long-term anticoagulation., Objectives: To assess the effects of electrical cardioversion of atrial fibrillation or flutter on the risk of thromboembolic events, strokes and mortality (primary outcomes), the rate of cognitive decline, quality of life, the use of anticoagulants and the risk of re-hospitalisation (secondary outcomes) in adults (>18 years)., Search Methods: We searched the Cochrane CENTRAL Register of Controlled Trials (1967 to May 2004), MEDLINE (1966 to May 2004), Embase (1980 to May 2004), CINAHL (1982 to May 2004), proceedings of the American College of Cardiology (published in Journal of the American College of Cardiology 1983 to 2003), www.trialscentral.org, www.controlled-trials.com and reference lists of articles. We hand-searched the indexes of the Proceedings of the British Cardiac Society published in British Heart Journal (1980 to 1995) and in Heart (1995 to 2002); proceedings of the European Congress of Cardiology and meetings of the Joint Working Groups of the European Society of Cardiology (published in European Heart Journal 1983-2003); scientific sessions of the American Heart Association (published in Circulation 1990-2003). Personal contact was made with experts., Selection Criteria: Randomised controlled trial or controlled clinical trials of electrical cardioversion plus 'usual care' versus 'usual care' only, where 'usual care' included any combination of anticoagulants, antiplatelet drugs and drugs for 'rate control'. We excluded trials which used pharmacological cardioversion as the first intervention, and trials of new onset atrial fibrillation after cardiac surgery. There were no language restrictions., Data Collection and Analysis: For dichotomous data, odds ratios were calculated; and for continuous data, the weighted mean difference was calculated., Main Results: We found three completed trials of electrical cardioversion (rhythm control) versus rate control, recruiting a total of 927 participants (Hot Cafe; RACE; STAF) and one ongoing trial (J-RHYTHM). There was no difference in mortality between the two strategies (OR 0.83; CI 0.48 to 1.43). There was a trend towards more strokes in the rhythm control group (OR 1.9; 95% CI 0.99 to 3.64). At follow up, three domains of quality of life (physical functioning, physical role function and vitality) were significantly better in the rhythm control group (RACE 2002; STAF 2003)., Authors' Conclusions: Electrical cardioversion (rhythm control) led to a non-significant increase in stroke risk but improved three domains of quality of life.

Background: Rates of myocardial infarction in firefighters are increased during fire suppression duties, and are likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assessed the effects of simulated fire suppression on measures of cardiovascular health in healthy firefighters., Methods: In an open-label randomized crossover study, 19 healthy firefighters (age, 41±7 years; 16 males) performed a standardized training exercise in a fire simulation facility or light duties for 20 minutes. After each exposure, ex vivo thrombus formation, fibrinolysis, platelet activation, and forearm blood flow in response to intra-arterial infusions of endothelial-dependent and -independent vasodilators were measured., Results: After fire simulation training, core temperature increased (1.0±0.1°C) and weight reduced (0.46±0.14 kg, P <0.001 for both). In comparison with control, exposure to fire simulation increased thrombus formation under low-shear (73±14%) and high-shear (66±14%) conditions ( P <0.001 for both) and increased platelet-monocyte binding (7±10%, P =0.03). There was a dose-dependent increase in forearm blood flow with all vasodilators ( P <0.001), which was attenuated by fire simulation in response to acetylcholine ( P =0.01) and sodium nitroprusside ( P =0.004). This was associated with a rise in fibrinolytic capacity, asymptomatic myocardial ischemia, and an increase in plasma cardiac troponin I concentrations (1.4 [0.8-2.5] versus 3.0 [1.7-6.4] ng/L, P =0.010)., Conclusions: Exposure to extreme heat and physical exertion during fire suppression activates platelets, increases thrombus formation, impairs vascular function, and promotes myocardial ischemia and injury in healthy firefighters. Our findings provide pathogenic mechanisms to explain the association between fire suppression activity and acute myocardial infarction in firefighters., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01812317., (© 2017 The Authors.)

Clinical Introduction: A 33-year-old man with no history of coronary artery disease presented to the rapid access cardiology clinic with an episode of atypical anginal chest pain. He had a 15 pack-year history of smoking and a family history of myocardial infarction under the age of 55. Physical examination and exercise ECG testing were unremarkable. On assessment in the cardiology clinic, blood sampling was notable for an elevated high-sensitivity troponin I of 61 ng/L (99% upper reference level, 34 ng/L). A coronary CT angiogram was performed (figure 1)., Question: Which of the following best explains this presentation? MyocarditisMyocardial bridgingKawasaki's diseaseAtherosclerotic plaque ruptureEosinophilic coronary monoarteritis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters., Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m³ particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4-6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure., Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all)., Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.

Objective: Galectin-3 is a pro-inflammatory, pro-fibrotic molecule implicated in the pathogenesis of heart failure, and associated with poor prognostic outcome. When measured following ST-elevation myocardial infarction (STEMI), a high plasma galectin-3 predicts greater 30-day morbidity and mortality, and increased heart failure incidence at a median of 2 years. This study aims to elucidate the temporal aspects of galectin-3 expression immediately post-STEMI and how expression relates to severity of myocardial injury., Methods: Plasma galectin-3 levels were compared in 53 STEMI patients and 23 control patients with stable angina. Consecutive plasma galectin-3 levels, measured at a mean of 30 hours (sample A) and 54 hours (sample B) post pain, and analysis of galectin-3 vs time since onset of pain/time since reperfusion allowed assessment of temporal expression in STEMI patients. Myocardial injury markers included troponin and left ventricular ejection fraction (LVEF) at primary percutaneous coronary intervention (PCI)., Results: Circulating galectin-3 levels were significantly higher in STEMI patients than control patients when measured at a mean of 30 hours post pain (t = 2.72, df = 66, P = 0.008). However, levels had significantly decreased when measured 24 hours later (t = 2.13, df = 47, P = 0.039), with a negative linear relationship apparent between plasma galectin-3 levels and time since reperfusion on univariate analysis (OR = 0.871, 95% CI = 0.779-0.975, P = 0.021). A significantly lower circulating galectin-3 concentration was also found for sample A in those reperfused within 3 hours post-onset of pain (OR 0.045, 95% CI 0.003-0.669, P = 0.029)., Conclusions: Plasma galectin-3 levels vary significantly following a STEMI over a short time period, in relation to timing of reperfusion.

Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG)., Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction., Findings: In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001)., Interpretation: (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease., Funding: Chief Scientist Office Scotland and British Heart Foundation., (Copyright © 2014 Joshi et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

The assessment of myocardial ischemia represents a cornerstone in our approach to coronary artery disease. Indeed many of the clinical decisions we make revolve around the results of stress testing, the assessment of coronary luminal stenoses and, more recently, fractional flow reserve measurements. Whilst the assessment of ischemia is often useful with respect to diagnosis and its treatment important in terms of symptom relief, whether ischemia directly leads to adverse cardiovascular outcomes, in particular myocardial infarction, is much more controversial. Indeed this is one of the key questions facing cardiology practice today and the focus of an ongoing multimillion-dollar study, the ISCHEMIA trial. In this editorial the authors examine some of the underlying evidence and ask the question: is ischemia itself really bad for you?

Objective: The mechanisms through which ω-3 fatty acids reduce adverse cardiac events remain uncertain. We aimed to investigate the effect of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in patients with coronary heart disease., Design: Randomised, double-blind, placebo-controlled, cross-over trial., Setting: Academic cardiac centre., Participants: 20 male patients with a previous myocardial infarction., Intervention: ω-3 Fatty acid supplementation (2 g/day for 6 weeks) versus olive oil placebo., Outcome Measures: Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 patients during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion., Results: All vasodilators caused dose-dependent increases in FBF (p<0.0001). ω-3 Fatty acid supplementation did not affect endothelium-dependent vasodilation with acetylcholine and substance P compared with placebo (p=0.5 and 0.9). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001), which was not affected by ω-3 fatty acid supplementation (p=0.9). ω-3 Fatty acids did not affect platelet-monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40., Conclusions: We have demonstrated that dietary supplementation with ω-3 fatty acids does not affect endothelial vasomotor function, endothelial t-PA release, or platelet and monocyte activation in patients with coronary heart disease. Cardiac benefits conferred by ω-3 fatty acids in coronary heart disease are unlikely to be mediated through effects on these systems.

Objective: The effects of ω-3 fatty acids on endothelial function, fibrinolysis and platelet function are uncertain. We investigated the effects of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in healthy cigarette smokers; a group at increased risk of myocardial infarction., Design, Setting, Participants: Twenty cigarette smokers were recruited into a randomised, double-blind, placebo-controlled, crossover trial of ω-3 fatty acid supplementation., Intervention: ω-3 fatty acid supplements (2 g/day) or placebo for a 6-week period., Main Outcome Measures: Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 smokers during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion., Results: All vasodilators caused dose-dependent increases in FBF (p<0.0001). Compared with placebo, ω-3 fatty acid supplementation led to greater endothelium-dependent vasodilatation with acetylcholine and substance P (p=0.0032 and p=0.056). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001) that was greater after ω-3 fatty acid supplementation compared with placebo (8.8±2.3 IU ml(-1) vs 3.6±1.1 IU ml(-1); p=0.029). ω-3 fatty acids did not affect platelet-monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40., Conclusions: We have demonstrated for the first time that ω-3 fatty acids augment acute endothelial t-PA release and improve endothelial vasomotor function in cigarette smokers. Improved endogenous fibrinolysis and endothelial function may represent important mechanisms through which ω-3 fatty acids confer potential cardiovascular benefits.

Background: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic., Methods/design: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014., Discussion: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease., Trial Registration: ClinicalTrials.gov Identifier: NCT01149590.

Background: Infusion of Mg for therapeutic purposes is still a matter for debate. Dosages vary considerably, yet subclinical effects on normal physiology are largely ignored. In human and animal models, interactions between Mg and insulin exist, thus we have investigated the effect of infusing Mg on serum insulin, ionised Mg (Mg(2+)) and Ca (Ca(2+)) and plasma glucose in human volunteers., Methods: Six male volunteers were infused with magnesium sulphate (MgSO(4)) dissolved in normal saline, using a high-dose "loading" bolus, followed by a lower-level "maintenance" period., Findings: Serum Mg(2+) rose rapidly throughout the bolus infusion, declined during the maintenance phase, but remained higher than pre-infusion levels throughout the experimental period; serum Ca(2+) rose when serum Mg(2+) was highest. Infusion of MgSO(4) had no effect on heart rate or blood pressure, but caused a rapid, pronounced drop in circulating fasting insulin (p<0.0005), which slowly recovered to basal values during the course of the maintenance infusion. A slight, transient rise in plasma glucose (p<0.05) concomitant with the decline in serum insulin was also observed., Interpretation: It is possible that the effect of Mg(2+) on insulin may have been due to antagonism of Ca(2+) entry in pancreatic beta-cells, the insulin decline causing a subsequent rise in circulating glucose levels. We suggest that these effects of MgSO(4) infusions should be considered where the aim is to achieve high doses of blood Mg(2+) levels by clinical intervention.

Background: The elderly account for an increasing proportion of the population and have a high prevalence of coronary heart disease. Percutaneous coronary intervention (PCI) is the most common method of revascularization in the elderly. We examined whether the risk of periprocedural complications after PCI was higher among elderly (age > or =75 years) patients and whether it has changed over time., Methods and Results: The Scottish Coronary Revascularization Register was used to undertake a retrospective cohort study on all 31 758 patients undergoing nonemergency PCI in Scotland between April 2000 and March 2007, inclusive. There was an increase in the number and percentage of PCIs undertaken in elderly patients, from 196 (8.7%) in 2000 to 752 (13.9%) in 2007. Compared with younger patients, the elderly were more likely to have multivessel disease, multiple comorbidity, and a history of myocardial infarction or coronary artery bypass grafting (chi(2) tests, all P<0.001). The elderly had a higher risk of major adverse cardiovascular events within 30 days of PCI (4.5% versus 2.7%, chi(2) test P<0.001). Over the 7 years, there was a significant increase in the proportion of elderly patients who had multiple comorbidity (chi(2) test for trend, P<0.001). Despite this, the underlying risk of complications did not change significantly over time either among the elderly (chi(2) test for trend, P=0.142) or overall (chi(2) test for trend, P=0.083)., Conclusions: Elderly patients have a higher risk of periprocedural complications and account for an increasing proportion of PCIs. Despite this, the risk of complications after PCI has not increased over time.

Background: Noncardiac surgery performed after coronary stent implantation is associated with an increased risk of stent thrombosis, myocardial infarction, and death. The influence of stent type and period of risk still have to be defined., Methods and Results: We linked the Scottish Coronary Revascularisation Register with hospital admission data to undertake a Scotland-wide retrospective cohort study examining cardiac outcomes in all patients who received drug-eluting or bare-metal stents between April 2003 and March 2007 and subsequently underwent noncardiac surgery. Of 1953 patients, 570 (29%) were treated with at least 1 drug-eluting stent and 1383 (71%) with bare-metal stents only. There were no differences between drug-eluting and bare-metal stents in the primary end point of in-hospital mortality or ischemic cardiac events (14.6% versus 13.3%; P=0.3) or the secondary end points of in-hospital mortality (0.7% versus 0.6%; P=0.8) and acute myocardial infarction (1.2% versus 0.7%; P=0.3). Perioperative death and ischemic cardiac events occurred more frequently when surgery was performed within 42 days of stent implantation (42.4% versus 12.8% beyond 42 days; P<0.001), especially in patients revascularized after an acute coronary syndrome (65% versus 32%; P=0.037). There were no temporal differences in outcomes between the drug-eluting and bare-metal stent groups., Conclusions: Patients undergoing noncardiac surgery after recent coronary stent implantation are at increased risk of perioperative myocardial ischemia, myocardial infarction, and death, particularly after an acute coronary syndrome. For at least 2 years after percutaneous coronary intervention, cardiac outcomes after noncardiac surgery are similar for both drug-eluting and bare-metal stents.

Aims: We sought to investigate the impact of body mass index (BMI) on long-term all-cause mortality in patients following first-time elective percutaneous coronary intervention (PCI)., Methods and Results: We used the Scottish Coronary Revascularisation Register to undertake a cohort study of all patients undergoing elective PCI in Scotland between April 1997 and March 2006 inclusive. We excluded patients who had previously undergone revascularization. There were 219 deaths within 5 years of 4880 procedures. Compared with normal weight individuals, those with a BMI > or =27.5 and <30 were at reduced risk of dying (HR 0.59, 95% CI 0.39-0.90, 95%, P = 0.014). There was no attenuation of the association after adjustment for potential confounders, including age, hypertension, diabetes, and left ventricular function (adjusted HR 0.59, 95% CI 0.39-0.90, P = 0.015), and there were no statistically significant interactions. The results were unaltered by restricting the analysis to events beyond 30 days of follow-up., Conclusion: Among patients undergoing percutaneous intervention for coronary artery disease, increased BMI was associated with improved 5 year survival. Among those with established coronary disease, the adverse effects of excess adipose tissue may be offset by beneficial vasoactive properties.

Objectives: This study was designed to establish the direct vascular effects of apelin in vivo in man., Background: Apelin is the endogenous ligand for the previously orphaned G-protein-coupled receptor, APJ. This novel pathway is widely expressed in the cardiovascular system and is emerging as an important mediator of cardiovascular homeostasis. In pre-clinical models, apelin causes venous and arterial vasodilation., Methods: Vascular effects of apelin were assessed in 24 healthy volunteers. Dorsal hand vein diameter was measured by the Aellig technique during local intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr(1))apelin-13, and sodium nitroprusside (0.6 nmol/min). Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of apelin-36 and (Pyr(1))apelin-13 (0.1 to 30 nmol/min) and subsequently in the presence or absence of a "nitric oxide clamp" (nitric oxide synthase inhibitor, L-N(G)-monomethylarginine [8 mumol/min], coinfused with nitric oxide donor, sodium nitroprusside [90 to 900 ng/min]), or a single oral dose of aspirin (600 mg) or matched placebo., Results: Although sodium nitroprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr(1))apelin-13 had no effect on dorsal hand vein diameter (p = 0.2). Both apelin isoforms caused reproducible vasodilation in forearm resistance vessels (p < 0.0001). (Pyr(1))apelin-13-mediated vasodilation was attenuated by the nitric oxide clamp (p = 0.004) but unaffected by aspirin (p = 0.7)., Conclusions: Although having no apparent effect on venous tone, apelin causes nitric oxide-dependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis.

Background: The US Food and Drug Administration recently concluded that data on off-label drug-eluting stent (DES) safety are limited. However, in actual clinical practice, DES are often used for off-label indications, and observational studies demonstrate that complications are higher when compared with on-label use. We aimed to determine whether clinical outcomes differ after DES and bare-metal stent implantation in a patient cohort defined by DES off-label indications., Methods and Results: We used the national revascularization registry in Scotland to identify patients who underwent coronary stenting for an off-label indication between January 2003 and September 2005. Individual-level linkage to comprehensive national admission and death databases was used to ascertain the end points of death, myocardial infarction, and target-vessel revascularization. We calculated propensity scores on the basis of clinical, demographic, and angiographic variables and matched DES to bare-metal stents on a 1:1 basis. The final study population consisted of 1642 patients, well matched for important covariables at baseline. Event-free survival was calculated over 24 months with the Kaplan-Meier method. All-cause death was more common after bare-metal stent implantation during follow-up (7.7% versus 6.6%; hazard ratio 0.63; 95% confidence interval, 0.40 to 0.99; P=0.04). No difference in the rates of myocardial infarction were noted (7.3% versus 7.5%; hazard ratio 1.02; 95% confidence interval, 0.69 to 1.54; P=0.92). Target-vessel revascularization was reduced in patients treated with DES (13.9% versus 10.7%; hazard ratio 0.67; 95% confidence interval, 0.49 to 0.93; P=0.02)., Conclusions: At 24 months, patients treated with DES for off-label indications had lower rates of death and target-vessel revascularization and similar rates of myocardial infarction, as compared with patients treated with bare-metal stents.

Objective: To determine whether drug-eluting stent (DES) use varies among Scottish hospitals, and the extent to which any variations are explained by differences between operators, patients and lesions., Methods: Multi-level analysis of consecutive patients treated with percutaneous coronary intervention (PCI) between April 2005 and March 2006 in Scotland, using the Scottish Coronary Revascularization Registry., Results: A total of 38 operators performed 5967 PCI procedures on 8489 lesions. Crude level of DES use was 47.6%, and the results varied among hospitals (range 30.6-61.8%, chi(2) = 341.6, P < 0.0001). There was significant between-operator variation in the null model. This was attenuated by the addition of hospital as a fixed effect. Nonetheless, the final model demonstrated significant between-operator variability [sigma(2) = 0.486 (0.249-0.971)] and between-hospital variation, after case-mix adjustment., Conclusions: Within Scotland, marked variation existed among hospitals in the use of DES. Operator was the most important factor at patient level, and hospital of treatment, rather than case-mix, was the most important modifier of between-operator variation. Patient selection for DES is complex and may contribute to much of the variations demonstrated. Consensus criteria would provide more detail than is included in current guidance, may aid decision-making for individual patients, reduce opportunity costs and ensure equity of access.

Background: Dietary intake of fish rich in omega-3 fatty acids is associated with a reduction in cardiovascular events. The mechanisms for this are uncertain and previous studies investigating effects on platelet function have produced inconsistent results. Platelet-monocyte aggregation is a sensitive marker of platelet activation and may contribute to the initiation and progression of atherothrombosis. This study assessed the effect of dietary intervention with oily fish on platelet-monocyte aggregation in healthy subjects., Methods: Fourteen subjects had their diet supplemented with 500 g of oil-rich fish per week for 4 weeks. A control group of 14 subjects received no dietary intervention over a 4-week period. Platelet-monocyte aggregates were assessed with flow cytometry., Results: Dietary intervention with fish led to an increase in omega-3 fatty acids in plasma phospholipids (14.2+/-3.4% versus 5.8+/-1.3%, P<0.001). In contrast to the control group, platelet-monocyte aggregates were reduced by 35% following dietary intervention with oily fish (16.0+/-9.0% versus 24.8+/-10.9%, P<0.01), and returned to basal levels 4 weeks after discontinuation of supplementation. There was an inverse correlation between platelet-monocyte aggregation and plasma omega-3 fatty acid concentrations (r=-0.421, P=0.006). There were no changes in the plasma markers of platelet activation, soluble P-selectin or soluble CD40 ligand., Conclusions: We have demonstrated, for the first time, that dietary intervention with oil-rich fish reduces platelet-monocyte aggregation in man. Our results suggest that reduced platelet activation provides a potential mechanism through which fish oils confer their cardiovascular preventative benefits.

Background: Sudden arousal has been associated with sudden cardiac death in individuals with ischemic heart disease, cardiac arrhythmias, and the congenital long QT syndrome. This study aimed to determine the effects of arousal on ventricular repolarization in normal individuals by examining the dynamic QT interval-heart rate relationship and T-wave morphology changes under various "arousal" scenarios., Methods: Eighteen healthy subjects (6 women and 12 men; median age, 22 years) underwent 4 separate 24-hour electrocardiogram recordings using 2-channel Holter recorders. The protocol contained 5 different arousal events: (1) natural waking (woke naturally, then stood up), (2) morning alarm (woken by alarm in the morning, then stood up); (3) night alarm (woken by alarm during the night, then stood up), (4) morning alarm-remain lying (woken by alarm in the morning but remained supine), and (5) lying to standing (stood up from a supine position during the day). Holter recordings were analyzed using a commercial package for dynamic assessment of the QT/RR relationship., Results: In the 20 minutes after arousal, no changes were seen in overall QT/RR relationship in any of the groups. However, marked T-wave morphology changes, including T-wave inversion, were observed in all the arousal events. Postural changes only accounted for a small proportion of change in T-wave morphology., Conclusions: In healthy subjects, noxious arousal causes marked changes in the morphology of the T wave. This may reflect abnormal adaptation of repolarization to sudden changes in heart rate and autonomic tone.

Hyperhomocysteinaemia is a prothrombotic condition that may cause oxidative endothelial injury and impair endogenous fibrinolysis. Vitamin supplementation enhances endothelial function in hyperhomocysteinaemic patients, but responses in patients with co-existing coronary artery disease have been variable. It is also unknown whether hyperhomocysteinaemia is associated with reduced fibrinolytic responses in patients with coronary artery disease. The study aims were to test the hypothesis that patients with recent myocardial infarction and hyperhomocysteinaemia have impaired endothelium-dependent vasomotion and fibrinolysis that is rectified by vitamin supplementation. From a cohort of 120 patients admitted with acute myocardial infarction, 18 patients were recruited from the upper (n=9) and lower (n=9) plasma homocysteine quartiles into a randomized double-blind placebo-controlled crossover trial. Following a 4-week course of placebo or folate/cyanocobalamin/pyridoxine supplements, FBF (forearm blood flow) was measured using venous occlusion plethysmography during intra-arterial substance P (4-16 pmol/min), acetylcholine (5-20 microg/min) and sodium nitroprusside (2-8 microg/min) infusions. All vasodilators caused dose-dependent increases in infused FBF (P<0.05). Patients in the upper homocysteine quartile (16.8+/-2.9 compared with 7.9+/-0.7 micromol/l; P=0.003) had reduced vasodilatation to acetylcholine (P=0.01) and substance P (P<0.05), but not sodium nitroprusside. There were no differences in substance P-induced tissue plasminogen activator release. Vitamin supplementation increased serum folate and vitamin B12 concentrations (P<0.05), but did not significantly lower homocysteine, or affect FBF or fibrinolytic responses. In patients with recent myocardial infarction, hyperhomocysteinaemia is associated with impaired endothelium-dependent vasodilatation, but no alteration in the acute fibrinolytic capacity. This endothelial vasomotor dysfunction is unaltered by vitamin supplementation.

This article briefly discusses the cardiac status of liver transplant recipients and their preoperative cardiac evaluation. It describes in detail perioperative and early and late postoperative complications as well as the cardiac problems associated with immunosuppression. The preoperative cardiovascular status of patients is important in determining how they cope with the stresses imposed by liver transplantation. Minor early cardiac events are common and may influence longer term cardiac morbidity. Immunosuppressive therapy may have short term effects but is likely to adversely affect long term cardiac risk.

Background: The anti-chlamydial antibiotic, azithromycin, may improve outcome in patients who survive an acute coronary syndrome. The mechanisms are, however, poorly understood. The aims of this study were to define any relationship between Chlamydia pneumoniae seropositivity and levels of specific markers of endothelial activation (soluble cell adhesion molecules) and more general markers of inflammation (C-reactive protein [CRP] and interleukin-6 [IL-6]) and to assess whether azithromycin had any effect on such markers., Methods: Patients who survived an acute coronary syndrome were randomized to receive treatment with azithromycin (n = 72) or placebo (n = 69) for 5 days. Before therapy, C pneumoniae IgA and IgG titers were checked, with serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, soluble E-selectin (sE-selectin), soluble P-selectin, high-sensitivity CRP, and IL-6. They were rechecked 3 months later., Results: There were no significant correlations between C pneumoniae titers and levels of CRP, IL-6, or soluble cell adhesion molecules. However, azithromycin treatment significantly reduced mean sICAM-1 levels (P =.006). This effect was more marked in patients with elevated titers of C pneumoniae IgA and IgG. Soluble E-selectin levels were also reduced in patients who were seropositive, but no effects were seen on other endothelial or inflammatory markers., Conclusions: After an acute coronary syndrome, a 5-day course of azithromycin reduces levels of sICAM-1, a marker of endothelial cell activation. Although these data suggest a potentially beneficial role for azithromycin, they should be interpreted with caution.

Background: Congestive heart failure is a common condition with high mortality. Many of these deaths are sudden and unexpected. Ventricular action potential, surface repolarization (QT interval), and dispersion of repolarization are prolonged in the failing heart, contributing to arrhythmogenesis and sudden death. We studied the relationship between QT and heart rate (RR interval) from ambulatory recordings using a novel method in patients with ischemic heart disease and varying degrees of left-ventricular impairment (IHD) and compared them to healthy subjects (HS). We compare the degree of abnormality with the functional impairment and ejection fraction., Methods: Using a previously described automated method for continuous estimation of the QT/RR characteristic that incorporates a correction formula for compensation of QT adaptation lag (VERDA, Del Mar Reynolds Medical Ltd., Hertford, UK), we compared recordings from 41 IHD patients with age-matched HS., Results: IHD Patients have prolonged 24-hour mean QTo (461 ms vs 426 ms, P < 0.01), and abnormal rate dependence relative to controls (24-hour mean slope: 0.20 vs 0.14, P < 0.001; J: 0.38 vs 0.28, P < 0.001). There is increased temporal variation in J with respect to HS. These abnormalities of repolarization increase with worsening NYHA class, but do not correlate with ejection fraction., Conclusions: The use of a universal correction formula to compare dynamic QT data in IHD patients is inappropriate. The observed progressive abnormalities may be responsible for the high incidence of sudden death through promotion of arrhythmias.

There are several case reports in the literature that describe cardiac complications in the first few weeks after orthotopic liver transplantation (OLT) in patients receiving tacrolimus as their primary immunosuppressive therapy. In this study, we investigated the cardiac function of patients on tacrolimus (T) compared with those on cyclosporin (C) (Neoral; Novartis, Basel, Switzerland) immunosuppression, after OLT, in a prospective randomized trial. We randomized 40 adult patients with cirrhosis to either T or C with azathioprine and prednisolone immunosuppression and followed up on them for 3 months after OLT. All had detailed clinical, biochemical, electrocardiographic and echocardiographic assessments at regular intervals. Abnormalities in cardiac function were common after OLT and significant deterioration in left ventricular diastolic function was demonstrable up to 3 months in both patient groups. Cardiac function was similar in the T and C arms and no significant electrocardiographic differences were observed, although reduced heart rate variability (HRV) and higher mean serum brain natriuretic peptide (BNP) levels were identified in the T group. The percentage increase in posterior wall thickness was higher in the T group. Cardiac dysfunction as shown by worsening echocardiographic measures of left ventricular diastolic function and by clinical cardiac events is common in the first 3 months after OLT in patients with cirrhosis. HRV and BNP values in the T group were worse than in the C group, but this was not translated to an increase in cardiac clinical events in this study.