High-dose tirofiban with enoxaparin and inflammatory markers in high-risk percutaneous intervention.

AIM: The study assessed the benefit of high bolus dose tirofiban (HD-tirofiban) with enoxaparin compared with HD-tirofiban with unfractionated heparin (UFH). The study examined markers of platelet activation, thrombin generation and inflammation. MATERIALS AND METHODS: The study is a prospective single centre open-label trial of patients with high-risk acute coronary syndrome treated with percutaneous intervention (PCI) who were randomized to anticoagulation with UFH or enoxaparin with HD-tirofiban (25 microg kg(-1) bolus). This study measured a panel of platelet activation markers, inflammatory biomarkers and thrombus generation between the two groups. RESULT: Sixty patients undergoing high-risk PCI were enroled in the study. Platelet inhibition as assessed by whole blood aggregometry following HD-tirofiban infusion was similar in both the UFH and enoxaparin groups. CD40 ligand expression on platelets was significantly reduced following PCI with HD-tirofiban and either UFH or enoxaparin. Following PCI, there were significant reductions measured in other markers of platelet activation including PAC-1, P selectin, factor V/Va, platelet-monocyte aggregates and monocyte expression of Mac-1 as determined by analysis of venous blood samples using flow cytometry. Prothrombin fragment 1+2, D-dimer, von Willebrand factor and high sensitive C-reactive protein levels were significantly less post PCI in the enoxaparin group compared with those patients receiving UFH. CONCLUSION: The combination of HD tirofiban with enoxaparin resulted in an attenuated inflammatory response when compared with that of the combination of HD tirofiban with UFH.

Five-year angiographic patency of radial artery bypass grafts.

BACKGROUND: Little information exists regarding mid-term and long-term patency of radial artery grafts. METHODS AND RESULTS: We performed restudy coronary angiography at 5.2+/-0.4 years after surgery on 50 asymptomatic patients who had undergone coronary artery bypass graft surgery, using at least 1 radial artery graft, to determine both graft patency and presence of narrowing. We examined preoperative clinical or angiographic variables that might predict graft occlusion. Radial artery graft patency was 89%, with 91% of grafts free of narrowing. Preoperative New York Heart Association anginal class < or =2, target vessel proximal stenosis < or =70%, and small target vessel supply territory were predictive of graft occlusion. CONCLUSIONS: At 5 years after surgery, radial artery grafts have disease-free patency rates that are similar to other graft types.

Growth factors released into the coronary circulation after vascular injury promote proliferation of human vascular smooth muscle cells in culture.

OBJECTIVES: This study sought to 1) assess in vivo release of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) into the coronary circulation after vascular injury in human subjects; and 2) evaluate mitogenic effects of PDGF and bFGF on the patient's own vascular smooth muscle cells (VSMCs). BACKGROUND: Circumstantial evidence suggests involvement of PDGF and bFGF peptides in the neointimal response to vascular injury. To date, no study has shown biologically active growth factors within the coronary circulation after vascular injury in human subjects. METHODS: In 18 patients, plasma PDGF AB, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) levels were measured in coronary sinus blood obtained before and up to 30 min after angioplasty. In five patients undergoing atherectomy, coronary sinus serum was added to cultured VSMCs derived from atherectomy tissue to assess the mitogenic potential of the serum. Mitogenicity attributable to PDGF and bFGF was determined using neutralizing antibodies to these factors. PDGF A, PDGF B and bFGF were localized within the atherectomy tissue using immunocytochemical analysis. RESULTS: Before angioplasty, PDGF AB, PF4 and beta-TG levels were elevated threefold in patients scheduled for angioplasty compared with those in control patients (p < 0.01). Within 5 min of angioplasty, PDGF AB levels increased twofold and returned toward preangioplasty levels at 30 min; PF4 and beta-TG levels remained elevated. Serum obtained at 30 min after atherectomy showed a sixfold increase in mitogenicity compared with preatherectomy serum (p = 0.01). This increase in mitogenicity was reduced by 20%, 40% and 65% in the presence of neutralizing antibodies to PDGF, bFGF and PDGF + bFGF, respectively. PDGF A, PDGF B and bFGF were visualized within the intima of the atherectomy tissue. CONCLUSIONS: The change in plasma PDGF level is consistent with first-phase release of PDGF after vascular injury. The increase in mitogenicity of serum suggests that PDGF and bFGF are biologically active.

Right heart thrombus: recognition, diagnosis and management.

The clinical, echocardiographic, hemodynamic, angiographic and pathologic features of five patients who had right heart thrombus are presented and their management is discussed. Two modes of presentation were recognized. In four patients, right heart thrombus complicated peripheral venous thrombosis and was associated with major pulmonary thromboembolism and right heart obstruction. In the fifth, it complicated myocarditis with heart failure and appeared to cause right heart obstruction. Two-dimensional echocardiography was diagnostic of right heart thrombus in four patients and showed evidence of right heart dysfunction in those with major pulmonary thromboembolism. The diagnosis was confirmed at surgery in three patients and at autopsy in one. Three patients successfully underwent surgical removal of the thrombus followed by anticoagulation. One patient was treated successfully with anticoagulation alone. The only death occurred in the patient with myocarditis.

Actinomycin-eluting stent for coronary revascularization: a randomized feasibility and safety study: the ACTION trial.

OBJECTIVES: We sought to demonstrate the safety and performance of the actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara, California) in the treatment of patients with single de novo native coronary lesions. BACKGROUND: Drug-eluting stents (DES) releasing sirolimus or paclitaxel dramatically reduce restenosis. The anti-proliferative drug, actinomycin D, which is highly effective in reducing neointimal proliferation in preclinical studies, was selected for clinical evaluation. METHODS: The multi-center, single-blind, three-arm ACTinomycin-eluting stent Improves Outcomes by reducing Neointimal hyperplasia (ACTION) trial randomized 360 patients to receive a DES (2.5 or 10 microg/cm(2) of actinomycin D) or metallic stent (MS). The primary end points were major adverse cardiac events (MACE) at 30 days, diameter stenosis by angiography, tissue effects, and neointimal volume by intravascular ultrasound (IVUS) at six months. When early monitoring revealed an increased rate of repeat revascularization, the protocol was amended to allow for additional follow-up for DES patients. Angiographic control of MS patients was no longer mandatory. RESULTS: The biased selection of DES patients undergoing IVUS follow-up invalidated the interpretation of the IVUS findings. The in-stent late lumen loss and that at the proximal and distal edges were higher in both DES groups than in the MS group and resulted in higher six-month and one-year MACE (34.8% and 43.1% vs. 13.5%), driven exclusively by target vessel revascularization without excess death or myocardial infarction. CONCLUSIONS: The results of the ACTION trial indicate that all anti-proliferative drugs will not uniformly show a drug class effect in the prevention of restenosis.

Pulmonary metastatic chondrosarcoma with intracardiac extension.

An unusual case of pulmonary metastatic chondrosarcoma with intracardiac extension is presented. Echocardiography and right heart catheterization with pulmonary angiography demonstrated that resection using cardiopulmonary bypass was possible in a situation initially considered to be inoperable.

Non ischaemic chest pain.

Chronic chest pain can be a considerable diagnostic challenge. A careful history will clarify its cause in most patients but investigations might be necessary for some, if only to provide a basis for reassurance and management.

Pre-hospital fibrinolysis in the management of patients with ST elevation acute coronary syndrome: review of the evidence, implementation and future directions.

Time to reperfusion is among the strongest predictors of clinical outcome in patients who present with ST elevation acute myocardial infarction. When time to access is equivalent, primary percutaneous coronary intervention has demonstrated superior outcomes to fibrinolysis. However, where significant delays exist in accessing percutaneous intervention, fibrinolysis has an important role. The potential for fibrinolysis delivery in the pre-hospital setting means that delays to primary percutaneous intervention need to be considered from the time that the patient becomes eligible for fibrinolysis in the field. This can be particularly challenging in patients with symptom duration ofless than two hours, as some evidence suggests fibrinolysis may be particularly beneficial in this early phase. Additionally, access to primary percutaneous intervention provided by an experienced operator, in a timely manner at any time of the day or night, is not an available option in many healthcare settings. This review focuses on the current evidence and practice of pre-hospital fibrinolysis and assesses potential roles for this therapy in the future.

Anti-Platelet Therapy for Acute Coronary Syndrome: A Review of Currently Available Agents and What the Future Holds.

Dual anti-platelet therapy remains a cornerstone in the management of patients suffering from acute coronary syndromes (ACS). The combination of aspirin and clopidogrel has been shown to result in significant reductions in cardiovascular end points including recurrent infarction and death in several randomised control trial of patients with ACS. However, many patients still experience ischaemic events on the combination of aspirin and clopidogrel. Aspirin is a relatively weak anti platelet agent. Clopidogrel is a pro drug that required activation by hepatic metabolism and hence its onset of action is delayed; there is genetic variation in the clinical response to the drug, the platelet inhibition is irreversible and no intravenous form is available. Consequently new anti-platelet agents have been developed to address the short falls of this combination therapy. This paper discusses existing anti-platelet regimes and focuses on novel antiplatelet agents that are currently under clinical evaluation.

Failure of current public educational campaigns to impact on the initial response of patients with possible heart attack.

AIMS: The National Heart Foundation of Australia recognizes that the risk of lethal arrhythmias is greater very early after the onset of myocardial infarction and that the more promptly flow can be restored in the infarct-related artery the greater will be the benefits for survival and preservation of heart function. The Heart Foundation has therefore conducted several public media campaigns to encourage patients to seek help more promptly and evaluated their impact. METHODS: Since 1996, we have conducted four surveys of delays preceding admission of patients to coronary care units throughout Australia to assess the impact of the Heart Foundation's media campaigns. Data were collected on 1665 patients who presented to 73 hospitals; information on patient delay was available for 1178 of them. RESULTS: There were no significant differences in patient delay (median 1.5-2.0 h) in the four surveys from 1996 to 2002, nor when patients were categorized by age, sex, presenting diagnosis or history of previous myocardial infarction or coronary revascularization by percutaneous or surgical techniques. CONCLUSION: New approaches are needed to reduce patient-related delay after the onset of symptoms suggesting possible myocardial infarction.

LATE assessment of thrombolytic efficacy with alteplase (rt-PA) six-24 hours after onset of acute myocardial infarction.

Conflicting results on the benefit of thrombolytic therapy administered six to 24 hours after the onset of myocardial infarction (MI) led to the LATE trial. Five thousand seven hundred and eleven patients were treated with recombinant tissue plasminogen activator (t-PA) or placebo, treatment was begun between six and 24 hours after the onset of infarction. For patients treated within 12 hours, there was a relative reduction in 35 day mortality of 25%, but no benefit for those treated at 12 to 24 hours. The benefits were confined to those whose treatment was begun within three hours of admission to hospital. These results widen the window for effective treatment from six to 12 hours after the onset of infarction, but emphasise the need for expeditious treatment when the diagnosis of MI is suspected.

Experience with a mobile coronary care unit in Brisbane.

We examined the performance of a hospital-based mobile coronary care unit staffed by emergency physicians, coronary care nurses, and ambulance personnel in a metropolitan setting (Brisbane, Australia). Our unit attended 2,260 calls during 18 months of operation. Standard dispatched ambulances arrived first to 78% of the 2,260 calls. Ten percent of these calls were to patients who had died or had arrested; 45% of these patients were found in ventricular fibrillation and 10% were discharged alive from the hospital. Survival was related to the performance of CPR before the arrival of the unit and to the finding of ventricular fibrillation. As the success of our unit was clearly inferior to that reported from centers where the first-responders are licensed to defibrillate, its operations have ceased and regular ambulance crews are being taught to recognize and treat patients with ventricular fibrillation.

Interventional management of acute myocardial infarction (AMI).

The best way to limit infarct size and improve survival in patients with early heart attacks is to restore as quickly as possible patency in the infarct-related artery and blood flow to the threatened myocardium. The value of thrombolytic therapy and aspirin has been shown in large clinical trials. A regimen of accelerated recombinant tissue plasminogen activator is more effective than those using streptokinase. In older patients, there is a greater risk of haemorrhagic stroke; nevertheless, thrombolytic treatment saves more lives because the mortality of myocardial infarction (MI) is higher. Thrombolytic therapy fails to restore blood flow sufficiently rapidly or completely in nearly one-fifth of patients. Its efficacy, therefore, has been compared with immediate or direct angioplasty (PTCA). If it can be done promptly enough, PTCA is superior in preventing recurrent ischaemia and the combined outcome of death or non-fatal reinfarction, and is associated with a lesser risk of intracranial haemorrhage. It may also be cheaper because patients spend less time in hospital and fewer of them require late revascularisation. PTCA should be considered for patients with cardiogenic shock or for those in whom there is a contraindication to thrombolytic therapy. The benefits of prompt treatment have been reduced by excessive delay in reaching hospital and door-to-needle time. After fibrinolysis, coronary angiography and PTCA may be reserved for those with spontaneous angina or exercise-induced ischaemia.

Beat-to-beat variation in echocardiographic measurements of left ventricular dimensions and function.

M-mode echocardiography was used to explore the extent of spontaneous variation in left ventricular dimensions and indices of systolic and diastolic function. Extended records made in 26 subjects at rest were digitized and analyzed by computer. We found considerable beat-to-beat variation, in that measurements of five or more consecutive cycles were necessary to provide representative values for minor axis dimensions, while the degree of scatter for derived indices of function was greater. This has to be recognized when serial echocardiography is used to study the progress of disease or the effects of treatment.

Left ventricular dimensions and systolic function during spontaneous heart rate changes: an echocardiographic study.

We examined the relationships between spontaneous heart rate (or conversely cycle length) changes and left ventricular diastolic dimensions and indices of systolic function in twenty-three subjects. In most there was clearly an inverse relationship between rate and these indices and nearly always a positive correlation between performance and end-diastolic dimension. Previously described relationship between heart rate and mean velocity of circumferential fiber shortening are applicable only when the heart rate is constant.

Successful total correction of Fallot's pentalogy in the seventh decade of life.

The patient described had correction of Fallot's pentalogy at the age of 61 and has been asymptomatic for a further five years. Survival with this disorder to this age is extremely rare, and successful surgery for cyanotic congenital heart disease in the seventh decade of life has apparently not been reported previously.

Consensus opinion and observer accuracy in electrocardiography with reference to coronary arteriographic information.

In this study reader performance in resting electrocardiographic (ECG) reading and case summary interpretation was investigated. Eight cardiologists were asked to read independently 105 paired ECG--Case summary sheets on either two or four occasions. The order of ECG--Case summary inspection for each sheet was randomized over trials. The results show low levels of inter- and intra-reader reliability when physicians report on ECG traces. Reference to coronary arteriographic information confirms that the resting ECG has limited utility in the detection of coronary artery disease.

Pericarditis in acute myocardial infarction.

In 1505 patients with acute myocardial infarction (MI) pericarditis was diagnosed most often in those with anterior transmural ECG changes. Those with pericarditis had a significantly greater hospital mortality and peak serum lactic dehydrogenase (LDH) levels and a greater incidence of left ventricular failure (LVF).

Echocardiographic comparison of haemodynamic effects of metoprolol and propranolol.

Metoprolol (200 mg daily) and propranolol (160 mg daily) were each given for one week to 11 normal subjects. The order of administration was randomized and not known to us during the study. Each period of treatment with active drug was followed by one week during which placebo tablets were taken. M-mode echocardiograms and blood pressure were recorded before entry to the trial, twice during each week of treatment with metoprolol or propranolol, and daily for three days and on the seventh day after stopping the drugs. Septal and posterior wall endocardial echoes were traced with an X-Y digitiser and left ventricular minor axis dimensions derived every 10 ms with a minicomputer. Both drugs reduced heart rate, cardiac output, and blood pressure. Systemic vascular resistance was increased significantly by propranolol, and with both agents was inversely related to heart rate, cardiac output, left ventricular diastolic dimension, and indices of contractility.

Indices of left ventricular systolic function derived by computer analysis of digitised M-mode echocardiograms.

In order to determine the value of computer-assisted analysis of echocardiograms we digitised 980 M-mode studies in normal subjects and patients with pressure and volume overload and heart muscle disease to derive left ventricular dimensions (D), peak systolic rate of change of dimension, normalized for instantaneous dimension (dD/dt/D), mean velocity of circumferential fiber shortening (mean Vcf) and percentage fractional shortening (%FS). The systolic phase indices which, in these patients averaged greater than normal in those with aortic stenosis and hypertrophic cardiomyopathy and lower than normal in those with aortic regurgitation, mitral stenosis and dilated cardiomyopathy, were closely related to each other in all categories of patients. Measurement of % FS appears to describe left ventricular function as well as the more complex indices (mean Vcf, peak dD/dt/D).