General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial.

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study).

BACKGROUND: Acute coronary, cerebrovascular, and peripheral vascular events have common underlying arterial pathology, risk factors, and preventive treatments, but they are rarely studied concurrently. In the Oxford Vascular Study, we determined the comparative epidemiology of different acute vascular syndromes, their current burdens, and the potential effect of the ageing population on future rates. METHODS: We prospectively assessed all individuals presenting with an acute vascular event of any type in any arterial territory irrespective of age in a population of 91 106 in Oxfordshire, UK, in 2002-05. FINDINGS: 2024 acute vascular events occurred in 1657 individuals: 918 (45%) cerebrovascular (618 stroke, 300 transient ischaemic attacks [TIA]); 856 (42%) coronary vascular (159 ST-elevation myocardial infarction, 316 non-ST-elevation myocardial infarction, 218 unstable angina, 163 sudden cardiac death); 188 (9%) peripheral vascular (43 aortic, 53 embolic visceral or limb ischaemia, 92 critical limb ischaemia); and 62 unclassifiable deaths. Relative incidence of cerebrovascular events compared with coronary events was 1.19 (95% CI 1.06-1.33) overall; 1.40 (1.23-1.59) for non-fatal events; and 1.21 (1.04-1.41) if TIA and unstable angina were further excluded. Event and incidence rates rose steeply with age in all arterial territories, with 735 (80%) cerebrovascular, 623 (73%) coronary, and 147 (78%) peripheral vascular events in 12 886 (14%) individuals aged 65 years or older; and 503 (54%), 402 (47%), and 105 (56%), respectively, in the 5919 (6%) aged 75 years or older. Although case-fatality rates increased with age, 736 (47%) of 1561 non-fatal events occurred at age 75 years or older. INTERPRETATION: The high rates of acute vascular events outside the coronary arterial territory and the steep rise in event rates with age in all territories have implications for prevention strategies, clinical trial design, and the targeting of funds for service provision and research.

Filter no reflow during percutaneous coronary interventions using the Filterwire distal protection device.

BACKGROUND: Distal protection devices are increasingly used to prevent embolization during percutaneous coronary interventions (PCI) in saphenous vein grafts (SVG) and native coronary arteries (NV). During interventions with the Filterwire device we have observed reduced flow that is reversible following removal of the filter (filter no reflow, FNR), which might be erroneously interpreted as true no reflow and might be associated with reduced capture efficiency of the basket. METHODS: We analyzed the incidence of FNR in 58 patients (60 lesions) at high risk of embolization undergoing PCI of either a SVG or a NV using the Filterwire (Boston Scientific, Natick, MA). Qualitative and quantitative angiographic analysis was performed, and the volume of collected debris was estimated using a photographic technique. RESULTS: In our population, about 1/3 of the cases showed FNR, which was associated with angiographically visible filling defects within the basket, indicating macroembolism. However some patients (especially those undergoing vein graft interventions) showed filling defects without FNR, and some others FNR without filling defects. Thus we tried to understand the predictors of FNR: FNR was associated with higher amount of collected debris (36.97 +/- 42.98 mm(3) vs. 11.31 +/- 18.47 mm(3), p = 0.005), was neither prevented by abciximab, nor predicted by high thrombotic burden, increasing stent volume or need for predilatation. When patient with and without angiographically evident macroembolisation were separately analyzed, a linear correlation of FNR with the quantity of debris was only apparent in the macroembolization group. CONCLUSIONS: Interventionalists should be aware of the "Filter No Reflow", a common but reversible angiographic complication when the Filterwire device is used. Reduced flow seen during these procedures should be treated conservatively. Mechanical obstruction of the filter, but also other mechanisms (pharmacologically active debris? platelet aggregates?) play a role in this phenomenon.

The warm-up effect protects against ischemic left ventricular dysfunction in patients with angina.

OBJECTIVES: The goal of this study was to investigate whether the "warm-up" effect in angina protects against ischemic left ventricular (LV) dysfunction. BACKGROUND: After exercise, patients with coronary disease demonstrate persistent myocardial dysfunction, which may represent stunning, as well as warm-up protection against further angina, which may represent ischemic preconditioning. The effect of warm-up exercise on LV function during subsequent exercise has not been investigated. METHODS: Thirty-two patients with multivessel coronary disease and preserved LV function performed two supine bicycle exercise tests 30 min apart. Equilibrium radionuclide angiography was performed before, during and up to 60 min after each test. Global LV ejection fraction and volume changes and regional ejection fraction for nine LV sectors were calculated for each acquisition. RESULTS: Onset of chest pain or 1 mm ST depression was delayed and occurred at a higher rate-pressure product during the second exercise test. Sectors whose regional ejection fraction fell during the first test showed persistent reduction at 15 min (68 +/- 20 vs. 73 +/- 20%, p < 0.0001). These sectors demonstrated increased function during the second test (71 +/- 20 vs. 63 +/- 20%, p = 0.0005). The reduction at 15 min and the increase during the second test were both in proportion to the reduction during the first test. Effects on global function were only apparent when the initial response to exercise was considered. CONCLUSIONS: The warm-up effect is accompanied by protection against ischemic regional LV dysfunction. The degree of stunning and protection after exercise is related to the severity of dysfunction during exercise, consistent with results from experimental models.

The effects of exogenous nitric oxide on smooth muscle cell proliferation following porcine carotid angioplasty.

OBJECTIVES: Nitric oxide reduces platelet adhesion and platelet-thrombus formation following angioplasty and inhibits smooth muscle cell (SMC) proliferation in vitro. In this study we investigated the effects of the nitric oxide donor molsidomine on SMC proliferation and intimal growth following experimental angioplasty. METHODS: Bilateral carotid angioplasty was performed in 24 anesthetized pigs. Animals were randomized to receive oral molsidomine (whose active metabolite is SIN-1; 0.3 mg/kg every 8 h; n = 12) or placebo (n = 12) for 48 h before angioplasty and until the arteries were removed either 7 or 21 days (n = 12 each group) later. SMC proliferation was quantified by immunocytochemical staining with an antibody to the proliferating cell nuclear antigen (PCNA) and morphometric changes by computerized planimetry. SMC's were identified by alpha-actin staining. RESULTS: After 3 weeks treatment with molsidomine there was a significant prolongation in bleeding time [mean +/- SEM] (151 +/- 6 to 187 +/- 7 s. P < 0.01) and a sustained increase in arterial wall cyclic GMP (6.57 +/- 1.29 to 13.24 +/- 1.02 pmol/mg protein, P < 0.05). Molsidomine significantly reduced intimal proliferation when compared with placebo in arteries with an intact internal elastic lamina at 7 days (4.3 +/- 0.7 vs. 9.6 +/- 1.9 PCNA index, P < 0.005) and medial proliferation at 7 days (2.4 +/- 0.2 vs. 4.2 +/- 0.7 PCNA index, P < 0.05) and at 21 days (1.3 +/- 0.1 vs. 1.9 +/- 0.2 PCNA index, P < 0.05) after angioplasty. In arteries with rupture of the internal elastic lamina, intimal and medial SMC proliferation were similar in molsidomine- and placebo-treated animals. Intimal cell number and intimal area were uninfluenced by treatment with molsidomine in either the presence or absence of rupture of the internal elastic lamina. CONCLUSIONS: These results show for the first time that exogenous nitric oxide inhibits SMC proliferation following balloon angioplasty in vivo. The antiproliferative effects of nitric oxide are overwhelmed when injury is severe and are not associated with a reduction in intimal thickening. The inhibitory effects of nitric oxide on platelet adhesion and SMC proliferation identify a possible role for high local concentrations of nitric oxide to modify the vascular response to balloon angioplasty.

Transradial arterial access catheter knots: how to stay out of trouble.

Transradial access has nowadays become a standard of care for percutaneous coronary angiography and intervention. This approach has demonstrated significant reduction in bleeding rate, length of hospital stay, and improvement in clinical outcomes when compared to the traditional transfemoral approach. Due to its advantages this new access is also increasingly being used in non-coronary visceral or peripheral interventions. However, this novel approach may lead to severe catheter kinking and twisting and further manipulation may be required to unravel the catheter and avoid complication. Purpose of this technical review is to present the current techniques and trends in preventing and resolving issues related to radial access catheter kinks.

Kinetics of smooth muscle cell proliferation and intimal thickening in a pig carotid model of balloon injury.

Restenosis as a result of neointimal smooth muscle cell accumulation is an important limitation to the effectiveness of balloon angioplasty as a treatment for end-stage atherosclerosis. Quantitative animal models allow the definition of pathophysiological mechanisms and the evaluation of new therapeutic strategies. In this study we quantified the time course of neointima formation by morphometry, and smooth muscle cell (SMC) proliferation by immunocytochemistry for proliferating cell nuclear antigen (PCNA), in the pig carotid artery 0-28 days following balloon injury. This led to two distinct kinds of injury observed also in clinical studies, namely medial dilatation or deep medial tearing with rupture of the internal elastic lamina. Dilatation injury alone led to medial enlargement and neointima formation by 7 days, which did not increase further up to 28 days. Medial enlargement was similar following rupture of the internal elastic lamina; however the sum of neointima formation plus the area of medial repair ('neomedia') increased progressively up to 21 days after balloon injury. Balloon injury increased the PCNA index of smooth muscle cells in the media underlying an intact internal elastic lamina maximally after 3 days. The PCNA index in the neointima and especially in the neomedia was greater and maximal after 7 days. Endothelial regrowth occurred by 21 days in the presence or absence of medial tears. Our results establish a quantitative pig model of balloon injury which will allow the assessment of new therapeutic strategies directed at two clinically relevant types of injury. Medial tearing is associated with an enhanced and localized proliferative response and may therefore be especially important in human restenosis.

Reciprocal changes in endothelial and inducible nitric oxide synthase expression following carotid angioplasty in the pig.

OBJECTIVE: Nitric oxide produced by nitric oxide synthase appears to have an important role in the regulation of arterial tone, platelet adhesion and smooth muscle cell proliferation. Our aim was to investigate the effects of balloon angioplasty on expression of endothelial NO synthase (cNOS) and inducible NO/synthase (iNOS) in the pig carotid artery and to relate any changes in expression to the processes of reendothelialisation and vascular repair. METHODS: Pigs were sacrificed at various time points to follow NOS expression in the neointima, media and regenerated endothelium. Immunocytochemical staining was used to localize cNOS and iNOS expression in the vessel wall. Relative amounts of cNOS were measured using quantitative in vitro alitoradiography. cNOS mRNA and iNOS mRNA was quantified by competitive PCR based on the sequenced cDNA of porcine cNOS and iNOS. RESULTS: Uninjured carotid arteries exhibited dense uniform luminal endothelial staining for cNOS. Balloon angioplasty caused denudation of cNOS immunoreactive cells and a marked reduction of cNOS gene expression but a complete recovery was noted by day 35. In normal uninjured carotid arteries no evidence of iNOS immunoreactivity was demonstrable but 24 h after injury, marked homogeneous iNOS immunoreactivity was detected in medial vascular smooth muscle cells. By 5 days, staining was evident in cells within the forming neointimal layer with no evidence of iNOS immunoreactivity in the media. iNOS immunoreactivity persisted in cells at the luminal surface at 7 days and iNOS gene expression appeared to be sustained in some animals with ruptured internal elastic lamina at 21 days. CONCLUSION: Balloon injury is associated with de-endothelialisation and a marked reduction in cNOS gene expression and activity. iNOS is induced throughout the arterial media within VSMC soon after balloon injury and persists for up to 21 days. These observations imply an important regulatory role for locally generated NO in the pathophysiological response to balloon injury.

Aortic atherosclerotic debris detected by trans-oesophageal echocardiography--a risk factor for cholesterol embolization.

The clinical syndrome of cholesterol embolization is uncommon but is associated with a poor prognosis. Patients with severe atheromatous disease of the aorta appear to be at particular risk from cholesterol embolization, particularly following vascular instrumentation or surgery. Trans-oesophageal echocardiography is the investigation of choice for imaging atherosclerotic disease of the aorta, and may be useful in assessing the risk of vascular procedures, and diagnostically helpful in patients with suspected cholesterol emboli syndrome. We report five cases of athero-embolism, and illustrate the role of trans-oesophageal echocardiography in making a diagnosis of cholesterol embolization.

Rupture of the atrial septum and tricuspid valve after blunt chest trauma.

A previously fit 19-year-old male driver was involved in an unrestrained, head-on collision. Transesophageal echocardiography revealed rupture of the chordae subtending both leaflets of the tricuspid valve with severe tricuspid regurgitation and disruption of the interatrial septum. When cardiac injury is suspected after blunt chest trauma, transesophageal echocardiography facilitates appropriate management as it provides safe, rapid, and accurate diagnostic images.

Time-related hemodynamic changes after aortic replacement with the freestyle stentless xenograft.

BACKGROUND: The Freestyle valve is a porcine aortic root fixed with net zero pressure across the cusps and treated with the anticalcification agent alpha-aminooleic acid. We evaluated the hemodynamic function of this stentless valve. METHODS: We implanted the valve into 80 consecutive patients scheduled to receive a bioprosthesis. Sixty-nine patients were more than 70 years old and 14 had calcified aortic sinuses. The "cylinder within a cylinder" implantation technique was used. Twenty-seven patients received coronary grafts, and 3 had mitral repair. All patients were studied echocardiographically during week 1 and 41 were studied at 6 months. RESULTS: Median ischemic time for isolated aortic valve replacement was 44 minutes. There were four hospital deaths, none valve related. No patient had more than trivial aortic regurgitation. Mean systolic gradients for valve sizes 21 to 25 mm fell significantly with time (p < or = 0.05) due to remodeling of the porcine root and early regression of left ventricular hypertrophy. Late hemodynamic function was equivalent to an aortic homograft. CONCLUSIONS: The Freestyle valve is easily implanted and has excellent hemodynamics. Transvalvular gradients decrease progressively.

Surgery for aortic stenosis in severely symptomatic patients older than 80 years: experience in a single UK centre.

OBJECTIVE: To ascertain the surgical risk and long term outcome of patients over 80 years old undergoing aortic valve replacement (AVR). DESIGN: Consecutive cases with respective case note audit and a telephone questionnaire. SETTING: Single UK cardiothoracic surgical centre. PATIENTS: 103 (48 male) patients over 80 years old undergoing AVR. The median age was 82 years (80-95 years) and 95 of 103 patients were in New York Heart Association (NYHA) class III or IV. METHOD AND RESULTS: Preoperative characteristics, operative course, cost, and outcome measures were ascertained. Mean bypass time was 56 minutes and 25 patients had simultaneous coronary artery bypass grafting. Overall mortality was 19 of 103. Univariate analysis of pertinent variables found that impaired renal function and peripheral vascular disease were significantly associated with early postoperative death. 10 of 12 patients requiring ventilation for more than 24 hours died. The 50% actuarial survival was 62 months. Late complications were uncommon with 92% of patients in NYHA class I or II at follow up. CONCLUSIONS: AVR in patients over 80 years old has a significant risk. However, those patients who survive experience significant benefit with good long term prospects for general health and social independence.

Aorto--bronchial fistula resulting from an accidental fall one year earlier.

A 75-year-old woman presented with massive haemoptysis 12 months after tripping over her shopping trolley. CT scanning and transoesophageal echocardiography demonstrated a traumatic false aneurysm which was confirmed at surgery to be partially ruptured. Aortobronchial fistula is an unusual cause of massive haemoptysis. It should be considered particularly in patients known to have abnormalities of the thoracic aorta.

Coronary artery aneurysm rupture mimicking dissection of the thoracic aorta.

Acute dissection of the ascending aorta may present with chest pain and haemopericardium. The following case illustrates an unusual differential diagnosis: rupture of a very large coronary artery aneurysm, diagnosed by transoesophageal echocardiography.

Can an echocardiographic score predict who will benefit clinically from balloon dilation of the mitral valve?

Deciding whether a patient with sub-optimal mitral valve anatomy will benefit from percutaneous mitral valvotomy remains a demanding clinical problem. We assessed the ability of an established echo score applied to transoesophageal images to predict absolute increases in mitral valve area and improvement in exercise capacity. Twenty five consecutive patients undergoing routine percutaneous mitral valvotomy were studied. Changes in exercise tolerance were measured by serial cardiorespiratory treadmill exercise testing. Before the procedure, exercise duration was directly related to mitral valve area (rs = 0.44, P < 0.05). Following percutaneous mitral valvotomy there was an increase in valve area (0.9 +/- 0.2 to 1.4 +/- 0.3 cm2, P < 0.0001) and repeat exercise testing demonstrated increases in exercise duration (470 +/- 220 to 610 +/- 240 s, P < 0.001) and peak VO2 (12.6 +/- 4.2 to 15.1 +/- 4.5 ml/kg/min, P < 0.01). There was an inverse correlation between the echo score and the increase in valve area (rs = -0.52, P < 0.05) but no relationship between the echo score and the increase in exercise duration or peak minute oxygen consumption (VO2). These data demonstrate that a score applied to transoesophageal images echocardiographic images can predict changes in mitral valve area but that the score fails to predict functional improvement for an individual patient. This suggests, therefore, that patients without contraindications to valvotomy whose valves have a high echo score should still be considered for valvotomy as they may benefit considerably from the procedure.

Coronary stenting of unprotected left main stem stenoses in elderly patients unsuitable for coronary surgery.

We describe five patients with severe unstable angina refractory to medical management in whom coronary angiography demonstrated a severe stenosis of the left main stem. Due to severe co-existing illnesses bypass surgery was deemed inappropriate. Angioplasty to the left main stem stenosis followed by stent deployment was performed. All five patients were successfully discharged from hospital.

Quantitative regional analysis of myocardial wall motion.

This paper presents a new technique for semiautomatic quantification of regional heart function from 2-D echocardiography. It uses a novel left ventricular border tracking algorithm based on shape-space ideas that we have recently described. In this paper, we show how to decompose the tracked output into clinically meaningful segmental parameters (wall excursion and thickening), using what we call a computational interpretational space (CIS). This leads to a quantitative and automatic scoring scheme for endocardial excursion and myocardial thickening. The method is illustrated on data from a patient with a myocardial infarct in the apical anterior/inferior region of the heart and is also assessed in a small retrospective dobutamine stress echocardiography clinical case study.

Periprocedural myocardial injury during elective percutaneous coronary intervention: is it important and how can it be prevented?

Periprocedural myocardial injury (PMI) is common after percutaneous coronary intervention (PCI). Periprocedural infarction (myocardial infarction type 4a) occurs after at least 10% of PCI procedures and has an impact on long-term prognosis. Measurement of biomarkers to allow assessment of PMI is an important tool for clinical and research purposes and should be routine after every PCI (troponin I or T and CK-MB). The importance of oral and intravenous antiplatelet agents and other drugs which have been proven to reduce PMI is discussed.

Spontaneous coronary artery dissection.

We present a case of a 43-year-old lady who presented with an acute coronary syndrome, but without any cardiac risk factors or previous cardiac symptoms, and who had a spontaneous coronary artery dissection. This was successfully treated with percutaneous coronary intervention. A brief discussion of this clinical entity and literature review is presented.