A cute pulmonary embolism (PE) is a potentially lifethreatening disease, spanning a wide spectrum of clinical outcomes.1 Hemodynamically stable patients with preserved right ventricular (RV) size and function are classified as lowrisk patients and have an excellent short-term prognosis once therapeutic levels of anticoagulation therapy are established. 2In contrast, hemodynamically unstable patients are at high risk of death from worsening RV failure and cardiogenic shock, with a hospital mortality rate >15%. 3,4 Approximately one quarter of hemodynamically stable patients with PE are at intermediate risk, with mortality rates ranging from 3% to 15% if imaging or biomarker evidence of RV dilatation or dysfunction is present. 5,6 Editorial see p 420 Clinical Perspective on p 486Systemic thrombolysis improves hemodynamic parameters 7 and reverses RV dilatation and dysfunction 8,9 but is associated with rates of major bleeding complications in up to 20% and intracranial hemorrhage in up to 3%.10,11 Systemic thrombolysis is standard treatment for high-risk PE 2,11 ; however, it is withheld in more than two thirds of such patients. 4,12 The use of systemicBackground-In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients. Methods and Results-Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20±0.14 and 1.17±0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism. Conclusions-In

The STAF pilot study showed no differences between the two treatment strategies in all end points except hospitalizations. These data suggest that there was no benefit in attempting rhythm-control in these patients with a high risk of arrhythmia recurrence. It remains unclear whether the results in the rhythm-control group would have been better if sinus rhythm had been maintained in a higher proportion of patients, as all but one end point occurred during AF.

The extent of ST segment elevation resolution conveys useful early information about outcome in an individual patient after acute myocardial infarction.

Aims Acute myocardial infarction complicated by cardiogenic shock is associated with an exceedingly high mortality, even if patients are treated with early reperfusion therapy. The aim of this study was to evaluate predictors of in-hospital mortality of a large cohort of consecutive patients with cardiogenic shock treated with primary percutaneous coronary intervention (PCI). Methods and results Between July 1994 and March 2001 all interventions performed in 80 centres in Germany were prospectively entered into the primary PCI registry of the ALKK. A total of 9422 procedures were registered, of these 1333 (14.2%) were performed in patients with cardiogenic shock. Total in-hospital mortality was 46.1% and was dependent on TIMI flow grade after PCI, with mortality rates of 78.2%, 66.1% and 37.4% in patients with TIMI 0/1, TIMI 2 and TIMI 3 flow, respectively. In a multivariate analysis left main disease, TIMI <3 flow after PCI, older age, three-vessel disease and longer time-intervals between symptom onset and PCI were significant independent predictors of mortality. The relative number of PCIs performed in patients with cardiogenic shock did not change significantly from 1995-2000. There was a significant decrease in mortality over the years (P for trend 0.02). Conclusions In-hospital mortality in patients with acute myocardial infarction complicated by cardiogenic shock remains high, even with early interventional therapy. However, our data demonstrate that the PCI in these high-risk patients is feasible in a wide spectrum of community hospitals with acceptable success rates. Our results seen in connection with the results of the randomized SHOCK study advocate an early invasive approach in younger patients with cardiogenic shock, while the best strategy in elderly patients is still a matter of debate.

In this large study administration of the NHE-1 inhibitor eniporide, before reperfusion therapy in patients with acute ST elevation MI, did not limit infarct size or improve clinical outcome.

Objectives Five drug classes have been shown to improve the prognosis of acute myocardial infarction in clinical trials: aspirin, b-blockers, statins, renin angiotensin system (RAS) blockers and thienopyridines. We aimed to assess whether the benefits of combining these drugs (termed optimal medical therapy, OMT), will result in a reduction of mortality in clinical practice. Design Nationwide registry Setting Hospitals with a cardiology unit or internal medicine department. Patients 5353 patients with acute myocardial infarction. At hospital discharge 89% received aspirin, 90%b-blockers, 84% statins, 81% RAS blockers, 70% a thienopyridine and 46.2% OMT. Interventions Pharmacotherapy Main outcome measures OR with 95% CI for mortality from myocardial infarction were calculated and adjusted for patient risk at baseline. Results Total mortality was reduced by 74% in patients receiving OMT (adj OR 0.26; 95% CI 0.18 to 0.38) versus patients receiving one or no drug. This was consistent in subgroups defined by STEMI/NSTEMI, diabetes and gender. Mortality was also reduced in patients receiving 2e4 drugs (adj OR 0.49; 95% CI 0.35 to 0.68), diabetic patients being the only subgroup with no significant effect. Analyses on the relative importance of either component revealed that withdrawal of b-blockers (adj OR 0.63; 95% CI 0.34 to 1.16) and/or a combination of aspirin/clopidogrel (adj OR 0.59; 95% CI 0.20 to 1.17) abolished the risk reduction conferred by OMT. Conclusions OMT over 1 year was associated with a significantly lower mortality of patients with acute myocardial infarction in clinical practice. However OMT is provided to less than half of eligible patients leaving room for substantial improvement.

Background Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction.Methods and Results Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin

Pharmacokinetics and fibrin specificity of alteplase (recombinant tissue-type plasminogen activator) were determined in 10 patients with acute myocardial infarction undergoing an accelerated infusion regimen during the alteplase/anistreplase patency study (TAPS). Fifteen milligrams of alteplase was administered as an intravenous bolus injection, followed by infusions of 50 mg over 30 min and 35 mg over a further 60 min. Mean steady state plasma concentrations of alteplase during the initial 30 min were 3.2 +/- 0.84 micrograms/ml, measured immunochemically, and 2.1 +/- 0.23 micrograms/ml, measured using a functional activity assay. These values were 45% and 51% higher, respectively, than those during the standard infusion schedule (p less than 0.01). However, the predominant plasma half-life determined by model fitting based on either assay (3.3 to 3.5 min) was unaltered compared with the standard regimen. Maximal concentrations of fibrin and fibrinogen degradation products were 5.1 +/- 2.2 and 1.9 +/- 1.1 micrograms/ml, respectively. Plasminogen decreased to 70% and alpha 2-antiplasmin to 35% of values before infusion. The results indicate that 1) improved coronary patency rates during "front-loaded" infusions can be rationalized in terms of higher plasma concentrations of both free and immunoreactive alteplase, 2) kinetic variables are comparable with those of other dosing strategies, and 3) fibrin specificity is not diminished relative to that of the standard infusion regimen.