Clinical outcomes of patients discharged from the Rapid Access Chest Pain Clinic with non-anginal chest pain: A retrospective cohort study.

BACKGROUND: The Rapid Access Chest Pain Clinic (RACPC) has become an important means of assessing patients who present with ischaemic or ischaemia-like symptoms of recent onset. Observations have shown that up to 70% are discharged with a diagnosis of non-anginal chest pain (NACP) and accordingly "reassured". This study aims to describe the actual clinical outcomes of this cohort of patients discharged from the RACPC. METHODS: We undertook a single centre retrospective cohort study at a tertiary cardiac hospital. The outcomes of unselected patients diagnosed with NACP and discharged from the RACPC between April 2010 and March 2013 at University Hospitals of Leicester (UHL) were recorded. Re-referrals to cardiology outpatient clinic and emergency hospital admissions for cardiovascular disease within 6 months, and the mortality rate at 12 months, were determined. RESULTS: 7066 patients were seen in the UHL RACPC during the 36-month period. 3253 (46.0%) were diagnosed with NACP and discharged. 7 (0.2%) were diagnosed with coronary artery disease (CAD) and 8 (0.25%) cases of acute coronary syndrome (ACS) identified during the review period. 11 (0.3%) patients died within 12 months of discharge from RACPC. No deaths were attributable to CAD. CONCLUSIONS: Comprehensive assessment using risk-stratification criteria in a nurse practitioner-led RACPC can accurately identify patients who are at low-risk for subsequent CAD. Despite contemporary National Institute for Health and Care Excellence (NICE) guidelines that shift focus away from a clinical judgement based approach, this strategy appears to robustly predict favourable outcomes in patients diagnosed with NACP.

Clinical trial: chest pain caused by presumed gastro-oesophageal reflux in coronary artery disease - controlled study of lansoprazole vs. placebo.

BACKGROUND: Gastro-oesophageal reflux (GER) and coronary artery disease commonly co-exist. Coronary artery disease patients may mistake GER-induced pain for cardiac pain or GER might provoke angina. AIM: To investigate if GER might contribute to nocturnal/rest chest pain among coronary artery disease patients. METHODS: Double-blind placebo-controlled crossover study investigating effect of lansoprazole on chest pain; 125 patients with angiographically proven coronary artery disease enrolled with at least one weekly episode of nocturnal/rest pain, randomized to lansoprazole 30 mg daily or placebo with crossover after 4 weeks. Symptoms recorded and QOL assessed by Nottingham Health Profile Questionnaire; ST segment depression episodes counted from 24 h electrocardiographic monitoring in final week of both periods. STATISTICAL ANALYSIS: ANCOVA with period and carryover analysis. RESULTS: In all, 108 patients completed the study. There was a modest increase in pain-free days on lansoprazole vs. placebo (P < 0.02), with fewer days with pain at rest (P < 0.05) and at night (P < 0.009) on lansoprazole vs. placebo, but no significant differences in ST segment depression episodes (P = 0.64). There was a trend for reduction in the 'physical pain' QOL domain. CONCLUSIONS: Among coronary artery disease patients, lansoprazole modestly increases pain-free days and reduces rest/nocturnal pain. As lansoprazole did not affect ST segments, this may be by suppression of GER-provoked pain misinterpreted as angina, rather than acid-provoked ischaemia.

Contemporary percutaneous coronary intervention--30 years in the making.

Angioplasty has come a long way in 30 years. It is now the dominant therapy for obstructive coronary disease and becoming so for acute myocardial infarction and for the majority of patients it is a simple, quick procedure with same- or next-day discharge with negligible morbidity. Many of the developments have been led by pioneers conducting independent large randomised trials, but there are issues still to resolve and there are new exciting developments such as bioabsorbable stents and stereotaxis in the wings. Many have a lot to be grateful for when we reflect on the insights and pioneering work of Andreas Gruntzig.

Role of non-invasive imaging in the management of coronary artery disease: an assessment of likely change over the next 10 years. A report from the British Cardiovascular Society Working Group.

Coronary angiography has been the gold standard for determining the severity, extent and prognosis of coronary atheromatous disease for the past 15-20 years. However, established non-invasive testing (such as myocardial perfusion scintigraphy and stress echocardiography) and newer imaging modalities (multi-detector x ray computed tomography and cardiovascular magnetic resonance) now need to be considered increasingly as a challenge to coronary angiography in contemporary practice. An important consideration is the degree to which appropriate use of such techniques impacts on the need for coronary angiography over the next 10-15 years. This review aims to determine the role of the various investigation techniques in the management of coronary artery disease and their resource implications, and should help determine future service provision, accepting that we are in a period of significant technological change.

Is there any place for oral anti-restenotic treatment in the era of drug eluting stents?

Are drug eluting stents destined to become the standard of care for all patients undergoing percutaneous coronary intervention, or are alternative therapeutic approaches preferable under certain circumstances?

Drug eluting stents in interventional cardiology -- current evidence and emerging uses.

Intervention in coronary artery disease is an area of cardiology where novel drugs, in the form of drug-eluting stents (DES), are being used increasingly commonly. DES are used across the whole range of coronary intervention, from stable angina patients with single or multivessel disease, acute coronary syndromes and acute myocardial infarction (i.e. primary angioplasty). Most recently, they are being tested in a particularly challenging subset of patients, those experiencing symptoms due to restenosis within a previously stented area of vessel (in-stent restenosis, ISR). This article summarises the rationale for the use of DES, across all these areas, focussing specifically on the emerging results of trials and registries examining the effectiveness of DES in acute myocardial infarction (AMI) and ISR. Drug-eluting stents represent a significant shift in the use of locally-delivered drugs in interventional cardiology. On the basis of encouraging trial data, including in the specific areas of in-stent restenosis and myocardial infarction, their use is becoming extremely widespread in place of bare-metal (drug-free) stents. This change is happening despite their high costs, relatively short follow-up data and concerns of possible unwanted effects, because of the weight of evidence that they are superior in preventing restenosis in many patient groups. This reduction is highly significant in angiographic terms and, to a lesser degree, in the prevention of clinically important restenosis requiring revascularisation, but not clearly in terms of overall mortality.

Clopidogrel induced urticarial rash in a patient with left main stem percutaneous coronary intervention: management issues.

Clopidogrel, an ideal treatment for prevention of subacute stent thrombosis, may not be feasible to use in every patient. Ticlopidine (plus aspirin) is a very good alternative, although the risks of life threatening neutropenia should mandate regular monitoring of blood counts. It is proposed that patients undergoing angioplasty and stenting should carry a warning card in an effort to make the public and general practitioners aware that antiplatelet treatment after angioplasty plays an important part in ensuring successful outcome.

Treating atherosclerosis: local drug delivery from laboratory studies to clinical trials.

Treating only the specific section of the vascular bed that is diseased appears to make sense. Giving drugs systematically to treat perhaps only a few centimetres of affected artery carries with it the risk of systemic side effects and reduced efficacy consequent on low concentrations of agent at the site of the problem. There has thus been great interest since the early 1990s in local drug delivery. Initial targets were the thrombotic response to plaque disruption but the problems arising from the incidental damage inflicted by devices used in interventional cardiology and the pathological consequences of this, namely smooth muscle cell initiated intimal hyperplasia, soon became the focus of pre-clinical studies. Problems to be overcome were the low efficiency of delivery of drugs and the low retention rates. Solutions to these problems included the development of strategies to target drugs, through the use of antibodies directed at antigens newly released at the site of damage. As it became clear that stents were becoming central to the attainment of a better clinical response to intervention by their inherent physical properties, it also became obvious that stents could be used to deliver agents. Issues such as which stent, how to load the drug onto the stent and what drug to use to inhibit the unwanted pathobiological response are ongoing issues.

Keeping the coronary arteries open: current opportunities.

Thrombolysis has reduced mortality from myocardial infarction, but effective opening of the artery with normal flow continues to be an important goal. Thrombolysis is not always as successful as it should be; alternatives include adjunctive therapy and mechanical opening of the arteries. In patients with acute coronary occlusion opening the artery should continue to be the primary aim.

Plasminogen activator and plasminogen activator inhibitor gene expression in human saphenous vein organ culture.

We describe the expression of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in saphenous vein culture. Smooth muscle cells (SMC) are quiescent in fresh tissue, whereas these cells acquire a proliferating phenotype when venous segments are cultured in the presence of serum. t-PA and PAI-1 were localized immunohistochemically and quantified using biochemical techniques. t-PA and PAI-1 mRNA was quantified by reverse transcription polymerase chain reaction (RT--PCR) assay. Immunostaining showed an increase in the positivity of proliferating cell nuclear antigen (PCNA) from 10-day tissue culture. Tissue sections from fresh vein showed minimal t-PA and maximal PAI-1 immunostaining. In contrast, 10-day cultures showed an increase in t-PA and a decline in PAI-1 staining. Biochemical analysis revealed a 118% increase in t-PA and a 50% decrease in PAI-1 antigen levels from 10-day tissue cultures. RT--PCR demonstrated that the mRNA encoding t-PA increased, while PAI-1 decreased after 10 days of culture. In conclusion, venous culture showed an up-regulation of t-PA and a repression of PAI-1 gene expression during SMC proliferation in the vessel wall. The PAI-1 repression observed in venous culture is in contrast to the situation observed in human atheroma. A shift in the t-PA/PAI-1 balance may have a role in vascular remodeling.

The acute management of myocardial infarction.

Acute myocardial infarction (AMI) is a common and potentially fatal condition. Primary prevention by reducing the risk of developing coronary atheroma disease has had an important effect on the incidence of the disease. However, for many, the first clinical presentation of their coronary atheroma is the development of acute coronary occlusion. The acute nature of such presentation is the result of the dynamic nature of the plaque event. Thus while measures such as increasing public education in areas of primary prevention are always important it needs to be recognised that real differences in outcome need to and can be made even once the event has occurred. Individuals developing chest pain need to be encouraged to present early, especially if they have a history of ischaemic heart disease. Once they have arrived at point of medical contact, rapid triage, early diagnosis and the institution of therapies designed to reduce the extent of myocardial damage are paramount.

Inhibition of vascular smooth muscle cell adhesion and migration by c7E3 Fab (abciximab): a possible mechanism for influencing restenosis.

OBJECTIVES: Brief intravenous administration of chimeric antibody c7E3 Fab during coronary angioplasty has been shown in some studies to provide long term protection against coronary events. Smooth muscle cell (SMC) adhesion and migration are key initial steps in the development of restenosis. The purpose of this study was to investigate the effect of c7E3 Fab on adhesion and migration of SMC to the extracellular matrix (ECM) proteins osteopontin (Opn) and vitronectin (Vn). METHODS: Adhesion of human vascular SMCs to ECM proteins was quantified using a CyQUANT assay kit. Migration of SMCs to Vn, Opn and PDGF was studied using a modified Boyden's chamber migration assay. Integrin expression was determined by immunoprecipitation. RESULTS: c7E3 Fab reduced SMC adhesion on Vn and Opn to 69.2+/-3.3% (P<0.001) and 52.5+/-4.8% (P<0.001) respectively, compared to adhesion without antibody present. This reduction was the same as that for anti-alpha(v)beta(3) integrin antibody LM609 (P=0.5). The combination of anti-alpha(v)beta(5) integrin antibody and c7E3 Fab had a greater effect than either antibody alone (P<0.001). c7E3 Fab reduced SMC migration to Vn and Opn to 51.6+/-8.9% (P<0.001) and 20.3+/-6.1% (P<0.001) respectively, compared to migration in the absence of antibodies. Again, similar results were seen with LM609. PDGF-induced SMC migration was also inhibited by c7E3 Fab (P=0.004) and LM609 (P=0.001), but to much less an extent. The migration SMCs from a culture found not to express the alpha(v)beta(3) integrin was unaffected by these antibodies, strengthening the argument that c7E3 Fab inhibits SMC function via this integrin. CONCLUSIONS: c7E3 Fab inhibits the adhesion and migration of SMCs via the alpha(v)beta(3) integrin. The inhibition, however, is partial, and varied depending on type of ECM protein and alpha(v)beta(3) integrin expression. Some of the clinical benefits of c7E3 Fab may be due to its effect on SMCs.