13N-ammonia rest/stress PET: folic acid improves global coronary vasoreactivity in coronary artery disease patients with normal or elevated homocysteine levels.

AIM: Hyperhomocysteinaemia (Hhcy) is known to be an independent risk factor for vascular disease. Coronary flow reserve (CFR) measured by positron emission tomography (PET) is a sensitive method to monitor the effects of pharmacologic interventions in Hhcy. We assessed coronary vascular reactivity by PET in patients with coronary artery disease (CAD) dependent on their homocysteine (Hcy) levels before and under high dose folic acid supplementation therapy (FAST). PATIENTS, METHODS: Twelve patients with CAD underwent rest/adenosine (13) N-ammonia PET for quantification of myocardial blood flow (MBF) and CFR before and after nine weeks FAST (10 mg/day). RESULTS: Folate levels increased from 21 +/- 6 to 210 +/- 34 microg/l (+900%, p < 0.0001) while Hcy levels decreased from 12.1 +/- 3.6 to 9.1 +/- 3.1 micromol/l ( - 25%; p < 0.01). Global resting MBF remained nearly unchanged after FAST, while stress MBF (from 2.61 +/- 0.93 to 3.25 +/- 1.15 ml/g/min; p = 0.05) and CFR (from 3.00 +/- 0.76 to 3.72 +/- 0.93 ml/g/min; p < 0.05; +24%) significantly increased in patients with normal and elevated Hcy levels (cut off 12 micromol/l). An inverse relation was found between Hcy and CFR (R = - 0.53; p = 0.08) and between Hcy and MBF at rest (R = - 0.62; p < 0.05) at baseline conditions, not persisting after FAST. CONCLUSION: Coronary vascular reactivity can be improved by FAST in patients with CAD and normal or elevated Hcy levels. FAST might lower an increased cardiovascular risk in CAD patients possibly by mechanisms that are not related to Hcy.

Predictive value of plasma plasminogen activator inhibitor-1 for coronary restenosis: dependence on stent implantation and antithrombotic medication.

BACKGROUND: The plasmin activation system is involved in the development of restenosis after percutaneous coronary interventions (PCI). Conflicting data exist concerning the role of plasminogen activator inhibitor-1 (PAI-1) and its predictive value for restenosis. OBJECTIVES: To evaluate the fibrinolytic response to injury after PCI with or without stent implantation on different antithrombotic medications and its relation to late restenosis. PATIENTS AND METHODS: Eighty consecutive patients with successful PCI without (balloon only; n = 37) or with stent implantation (stent; n = 43) on different antithrombotic regimes (balloon only, aspirin; stent, aspirin/coumadin/dipyridamole vs. aspirin/ticlopidine). Blood samples were taken at baseline and up to 7 days after PCI and PAI-1 active antigen and tissue plasminogen activator (t-PA) antigen were determined. Restenosis was angiographically determined after 6 months. RESULTS: PCI increased both t-PA and PAI-1 levels (P < 0.001), with a significant prolonged and pronounced increase in stent vs. balloon-only patients (P < 0.05). Restenosis (stent 26%; balloon 38%) was significantly correlated to an attenuated PAI-1 increase after 24 h in the ticlopidine group (P = 0.007; restenosis, relative Delta PAI-1 + 50 +/- 28%; non-restenosis, + 139 +/- 50%), but not in the coumadin group. In the balloon-only group late restenosis (ISR) was associated with a trend for an augmented PAI-1 increase after 24 h. CONCLUSIONS: Coronary stent implantation significantly increases t-PA and PAI-1 plasma levels up to 1 week compared with balloon angioplasty alone. ISR in ticlopidine-treated patients was associated with an attenuated early PAI-1 active antigen increase. A less than 50% increase 24 h after stent implantation under ticlopidine treatment may identify patients at risk for the development of ISR.

Hemodynamic effects of a continuous infusion of levosimendan in critically ill patients with cardiogenic shock requiring catecholamines.

BACKGROUND: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with decompensated heart failure with preserved arterial blood pressure. Data on its use in patients with cardiogenic shock are rare. The present series describes the 24-h hemodynamic effects of levosimendan as add-on therapy in desperately ill patients with cardiogenic shock requiring catecholamines. METHODS: Ten patients with cardiogenic shock received levosimendan as continuous infusion of 0.1 microg kg(-1) min(-1) for 24 h. The patients were otherwise unselected. Hemodynamic measurements were routinely performed at baseline (time 0) and at 1, 8, 16 and 24 h after start of levosimendan (LS) using a Swan-Ganz thermodilution catheter. RESULTS: During the levosimendan infusion there was a significant increase in cardiac index from 1.8 +/- 0.4 to 2.4 +/- 0.6 L*min-1*m-2 (P = 0.023) and a significant decrease in systemic vascular resistance from 1559 +/- 430 to 1109 +/- 202 dyn*s*cm-5 (P = 0.001), respectively. Changes in catecholamine dose, and in systolic and diastolic blood pressure were not significant. Given the individual response to LS, 8/10 patients showed an increase in left ventricular stroke work index under reduced or roughly unchanged preload conditions after 8 h. CONCLUSION: This series shows that a LS infusion is feasible and able to improve hemodynamics in severely compromized, critically ill patients with cardiogenic shock requiring catecholamine therapy. Its potential advantages when compared with other inotropes are unclear. To clarify the potential role of LS in this clinical setting randomized controlled trials on hemodynamic and mortality endpoints are needed.

Homocysteine plasma levels in young patients with coronary artery disease. Relation to history of acute myocardial infarction and anatomical extent of disease.

Although there is considerable epidemiologic evidence for a relationship between plasma homocysteine (Hcy) levels and cardiovascular disease, not all prospective studies have shown such a relationship. Furthermore, data concerning the role of hyperhomocysteinemia in patients with premature coronary artery disease (CAD) are rare. It was the aim of the study to investigate a possible association between Hcy plasma levels in young patients with the extent of CAD and the history of myocardial infarction (MI). A cohort of 94 patients was examined for conventional risk factors and the history of previous transmural MI. Furthermore, coronary angiography was performed to assess the anatomical extent of vessel disease. Plasma Hcy levels were measured by use of a commercial enzyme-linked immunosorbent assay. Only a history of previous MI was significantly associated with hyperhomocysteinemia. There was no relationship between elevated Hcy levels and the anatomical extent of vessel disease in patients with premature CAD. Our data may indicate that hyperhomocysteinemia represents an independent risk factor for acute coronary thrombosis rather than for the development of coronary sclerosis. Thereby, hyperhomocysteinemia may influence the clinical situation after plaque rupture not only by prothrombotic action but also by favouring endothelial dysfunction and vasospasm.

Termination of recent-onset atrial fibrillation/flutter in the emergency department: a sequential approach with intravenous ibutilide and external electrical cardioversion.

Safety and effectiveness are the goals in treating patients with arrhythmias. In an open prospective study, we observed the efficacy and safety of up to 2 mg intravenous ibutilide, a new class III antiarrhythmic agent in haemodynamically stable patients presenting in the emergency department (ED) with symptoms of recent-onset (<48 h) atrial fibrillation/flutter. Arrhythmia termination within 90 min, haemodynamic parameters and proarrhythmic effects were assessed. Non-responders to the ibutilide infusion underwent external electrical cardioversion. We included 51 patients. In 31 patients therapeutic intervention with intravenous ibutilide was successful within 90 min (61%). In another seven patients conversion to sinus rhythm occurred after 90 min without any other intervention (14%). Blood pressure remained stable and no relevant proarrhythmic effects were observed. The 13 patients who did not respond to ibutilide treatment underwent successful external electrical cardioversion. The overall conversion rate was 100%. Forty-seven patients (92%) were discharged within a median of 9 h and managed as outpatients. In conclusion, in haemodynamically stable patients with recent-onset atrial fibrillation/flutter intravenous ibutilide and external electrical cardioversion for conversion to sinus rhythm turned out to be effective and safe. The short duration of admission makes this strategy attractive for use in the ED.

Plasma levels of C-reactive protein after coronary stent implantation.

AIMS: This study was designed to investigate the role of inflammation on the occurrence of angiographic restenosis 6 months after coronary stent implantation and the influence of different kinds of antithrombotic and antiplatelet strategies on inflammation. METHODS AND RESULTS: In an open randomized trial, 40 consecutive patients were treated with aspirin (100 mg. day(-1)) and either ticlopidine (2x250 mg. day(-1)) (n=17), or phenprocoumon (INR 2.0-3.0) and dipyridamole (3x160 mg. day(-1)) (n=23) after successful elective coronary stent implantation. Plasma levels of C-reactive protein were determined one day before stent implantation and serially thereafter twice daily up to 120 h. C-reactive protein plasma levels increased significantly (P<0.0001) after stent implantation. Phenprocoumon and dipyridamole or ticlopidine had no effect on C-reactive protein plasma levels (P=0.51) or the occurrence of angiographic restenosis (P=0.48). C-reactive protein plasma levels were significantly higher in patients with lesion type C compared to types A or B (P=0.035), respectively. C-reactive protein plasma levels were significantly higher and mean shoulder levels occurred 48 h later in patients with restenosis compared to patients without restenosis after 6 months (P=0.038). CONCLUSIONS: Elevated C-reactive protein plasma levels still persisting 96 h after stent implantation might reflect a prolonged inflammatory reaction to coronary stent implantation which might causally be involved in pathophysiological mechanisms leading to restenosis.

The association between C-reactive protein on admission and mortality in patients with acute myocardial infarction.

OBJECTIVE: In patients presenting with acute myocardial infarction the pathophysiologic and prognostic value of serum C-reactive protein is not well defined. This study assessed the association between serum C-reactive protein levels on admission and mortality in patients admitted because of acute myocardial infarction. DESIGN: Retrospective cohort study. SETTING: Tertiary care centre. PATIENTS: A total of 729 patients with acute myocardial infarction admitted within a period of 3 years. MAIN OUTCOME MEASURES: C-reactive protein levels on admission, cardiovascular risk factors and survival within the observational period. RESULTS: Within the 3-year observational period, 118 patients died of a cardiovascular cause. With increasing serum C-reactive protein levels (<0.5, 0.5 to <2, 2 to <5, 5-10 and >10 mg dL-1) mortality also increased (14%, 19%, 20%, 39% and 28%, respectively). When controlling for the confounding effect of age, thrombolytic treatment, the time interval between onset of pain and admission, smoking, diabetes mellitus, hypercholesterolemia, hypertension, and elevated creatine kinase on admission in a multivariate Cox regression model, there was only a weak and nonsignificant association between increased serum C-reactive protein and the risk of death. CONCLUSIONS: Patients with elevated concentrations of serum C-reactive protein admitted to the hospital because of acute myocardial infarction are at an increased risk of dying. This association is however, largely explained by other baseline variables, in particular by an estimate of the duration of myocardial ischaemia. If C-reactive protein measured by means of an ultra-sensitive assay is more suitable for risk stratification of unselected patients with acute myocardial infarction, needs further study.

Acute renal infarction. Clinical characteristics of 17 patients.

We analyzed the medical records of patients with an established diagnosis of acute renal infarction to identify predictive parameters of this rare disease. Seventeen patients (8 male) who were admitted to our emergency department between May 1994 and January 1998 were diagnosed by contrast-enhanced computed tomography (CT) as having acute renal infarction (0.007% of all patients). We screened the records of the 17 patients for a history with increased risk for thromboembolism, clinical symptoms, and urine and blood laboratory results known to be associated with acute renal infarction. A history with increased risk for thromboembolism with 1 or more risk factors was found in 14 of 17 patients (82%); risk factors were atrial fibrillation (n = 11), previous embolism (n = 6), mitral stenosis (n = 6), hypertension (n = 9), and ischemic cardiac disease (n = 7). All patients reported persisting pain predominantly from the flank (n = 11), abdomen (n = 4), and lower back (n = 2). On admission, elevated serum lactate dehydrogenase was found in 16 (94%) patients, and hematuria was found in 12 (71%) of 17 patients. After 24 hours all patients showed an elevated serum lactate dehydrogenase, and 14 (82%) had a positive test for hematuria. Our findings suggest that in all patients presenting with the triad--high risk of a thromboembolic event, persisting flank/abdominal/lower back pain, elevated serum levels of lactate dehydrogenase and/or hematuria within 24 hours after pain onset--contrast-enhanced CT should be performed as soon as possible to rule out or to prove acute renal infarction.

Sustained ventricular tachycardia in the emergency department.

The aim of the study was to evaluate the demographics, haemodynamics, ECG characteristics, underlying disease, tachycardia termination and outcome of patients with sustained ventricular tachycardia (VT). We registered 75 patients presenting with VT (51 male, median age 63) from December 1993 to August 1998 in our emergency department (ED). Seventeen of these patients were haemodynamically unstable (23%), and 58 patients were stable (77%); there was no difference in the tachycardia cycle length (median 320 ms) and QRS width (median 140ms) between the two groups; however, five of the seven patients with polymorphic VT pattern were in the unstable group. Ischaemic heart disease was the underlying disorder in 57 patients (76%). Acute myocardial infarction (AMI) was present in 12 of the 58 stable (21%) compared to 11 of the 17 unstable (65%) patients. In three patients (4%) VT terminated spontaneously, in 34 patients (45%) VT was terminated by first-line intravenous drug therapy, and in 38 patients (51%) including all 17 unstable and 22 stable who failed to respond to the intravenous antiarrhythmic therapy challenge out of 55 patients, VT was terminated by electrical therapy. Within 2 days, 48 patients (64%) were transferred to an open ward, 13 (17%) still needed intensive care, nine (12%) were discharged to home and five (7%) died. Death occurred due to cardiac failure from AMI with extensive anterior wall infarction in three patients, and due to constrictive pericarditis and reocclusion of stented LAD each in one patient. At presentation in the emergency department, the majority of the patients with VT were haemodynamically stable, thus allowing first-line antiarrhythmic drug administration. However, in the course of the disease, half needed electrical therapy for definitive termination of the tachycardia. Therefore, direct current cardioversion must be available in the emergency department. Haemodynamic instability and death occurs significantly more often if VT occurs during the course of AMI.

[Acute coronary syndromes: physiopathology and therapeutic aspects]. / Akute Koronarsyndrome: Pathophysiologie und therapeutische Aspekte.

This article discusses recent developments in the field of acute coronary syndromes including pathophysiological mechanisms as well as therapeutic strategies. A plaque disruption is caused by different stimuli in a plaque prone to rupture, i.e. a plaque with a lipid-rich core and high local concentration of inflammatory cells (T-cells, monocytes/macrophages, mast cells). These cells are capable of producing matrix degradation products and can reduce stability of a plaque. Thrombus formation, based on platelet activation and aggregation as well as fibrin formation, is the main consequence of plaque disruption. Depending on the degree of thrombus formation occlusion is followed clinically by unstable angina (subtotal occlusion) or by acute myocardial infarction (total occlusion). Accompanying vasoconstriction may further aggravate the situation. Principles of therapy are thrombus dissolution as well as prevention of new thrombus formation: main goals of thrombolytic therapy in acute myocardial infarction are a prompt (less than 3 hours), complete, and sustained (prevention of early thrombotic reocclusion) reperfusion.

Primary PTCA versus thrombolysis with tPA in acute myocardial infarction: a formal cost-effectiveness analysis.

AIMS: Information concerning the cost-effectiveness of primary percutaneous transluminal coronary angioplasty (PTCA) compared to thrombolytic treatment with tissue plasminogen activator (tPA) for the management of acute myocardial infarction (AMI) is limited. The existing data are derived from studies using a wide range of intervention, re-intervention and a high rate of mortality. The present study examined the cost-effectiveness of primary PTCA compared to thrombolytic treatment with tPA in the setting of AMI by applying data from published prospective randomised studies. METHODS AND RESULTS: We performed a formal cost-effectiveness analysis. As estimates for "cost" of therapy we applied the reimbursement paid by the public health insurance organisations in Austria. Coronary intervention rates and re-intervention rates were extracted from published studies. Assuming a moderately reduced in-hospital mortality for patients treated with primary PTCA (4.8%) compared to tPA (6.6%) on the basis of AMI in a 60-year-old male, the estimated additional cost per life saved was 274.-ECU (95% confidence interval 231.- to 318.-ECU). However, the cost per life saved was sensitive to the given range of intervention and re-intervention rates (range 2,518.-ECU gain to 9,560.-ECU additional cost). CONCLUSIONS: Assuming a moderate in-hospital survival benefit from treatment with primary PTCA in patients with AMI, PTCA seems to be cost effective in comparison to treatment with tPA--at least from the perspective of cost reimbursement by public health insurance organisations.

Fibrinolytic response to venous occlusion compared to physical stress test in young patients with coronary artery disease.

INTRODUCTION: Venous occlusion (VO) and exercise stress (ES) are stimulators of the fibrinolytic system. Aim of this study was to answer which of both stimulation tests is more useful in patients with symptom-limited coronary artery disease (CAD) to evaluate possible defects in the fibrinolytic system. METHODS AND RESULTS: We investigated 20 patients (M/F = 15/5; mean age = 36.7 years) with angiographically proven CAD for their plasma levels of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-type-1 (PAI-1) at basal conditions as well as after VO and at maximal ES (standardised bicycle stress test) and compared the data to those obtained from 12 sex- and age-matched healthy controls (M/F = 9/3; mean age = 40.4 years). At basal conditions mean t-PA activity and t-PA antigen plasma levels were within the normal range and comparable between the two study groups. After both VO and maximal ES, mean t-PA activity and t-PA antigen levels increased significantly more in the control group as compared to the CAD group. Mean PAI-1 activity plasma levels were significantly higher in the CAD group at basal conditions before VO (patients 7.0 +/- 3.1; controls 3.9 +/- 3.9; IU/ml; p = 0.025) as well as before ES (patients 8.1 +/- 3.5; controls 4.3 +/- 3.8; IU/ml; p = 0.009). PAI-1 activity plasma levels showed a significant decrease for patients and controls only after VO, while PAI-1 activity was not significantly decreased in both study groups at maximal ES. DISCUSSION: The significantly higher increase in mean plasma levels of t-PA activity and t-PA antigen after VO compared to ES in both groups might be explained by the fact that CAD induced symptoms in the patients during ES thus permitting only 80% of their age, sex, and body mass index related optimal work load. CONCLUSION: VO and ES are applicable triggers of the endogenous fibrinolytic system in healthy subjects and patients who are not limited in their physical exercise. Standardised VO appears to be superior to ES as stimulation test of the endogenous fibrinolytic system in patients with symptomatic CAD.

Restoration of coronary blood flow by single bolus injection of the GPIIb/IIIa receptor antagonist c7E3 Fab in a patient with acute myocardial infarction of recent onset.

It has been debated that primary coronary angioplasty could be more effective if immediate antithrombotic therapy would contribute to a faster recanalization of the infarct-related artery. This is the first report of a patient who presented at the emergency department with acute anterolateral myocardial infarction, in whom a single bolus injection of c7E3 Fab (0.25 mg/kg body weight) led to complete reperfusion of the infarct-related coronary artery during organization time for planned acute coronary angioplasty. Pain relief 15 min after initiation of therapy and ST-segment resolution of > 50%, as well as occurrence of idioventricular rhythm 30 min thereafter, were suggestive of successful recanalization before the coronary intervention was started. Diagnostic coronary angiography at 90 min revealed TIMI-grade 3 flow in the infarct-related coronary artery with only moderate luminal irregularities. Bolus administration of c7E3 Fab could be effective for dissolving platelet-rich thrombi in the early stage of acute myocardial infarction (AMI) and may therefore represent a promising "bridging" therapy in patients with AMI elected for primary coronary angioplasty.

Clofibrate elevates enzyme activities of the tricarboxylic acid cycle in rat liver.

Activities of the tricarboxylic acid cycle enzymes were measured in subcellular fractions of liver from rats that had been fed clofibrate for 3 weeks. Large changes in these activities per gram tissue were found in the large particle fraction, which also showed an increase in total protein concentration of 76% under clofibrate treatment. The three regulatory enzymes of the cycle, namely citrate synthase, NAD(+)-linked isocitrate dehydrogenase, and 2-oxoglutarate dehydrogenase were significantly enhanced by 24% (P < 0.02), 54% (P < 0.02), and 153% (P < 0.005), respectively. Fumarase and malate dehydrogenase rose by 71% (P < 0.005) and 95% (P < 0.02), whereas succinate dehydrogenase remained unchanged. Enhancement of the citrate synthase, NAD-isocitrate dehydrogenase, and 2-oxoglutarate dehydrogenase may play a role in decreasing intracellular availability of acetyl-CoA for lipid metabolism.