Background: Oral factor XIa (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without significantly increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6–2 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on factor XIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% were women, 51% had ST-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10, 20, 50 mg, and placebo (pooled asundexian vs. placebo: HR 0.98, 90% CI 0.71–1.35). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10, 20, 50 mg, and placebo (pooled asundexian 20 and 50 mg vs. placebo: HR 1.05, 90% CI 0.69–1.61). Conclusions: : In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients following acute MI.

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Brain natriuretic peptide (BNP) is a diagnostic marker for left ventricular dysfunction. Sepsis and septic shock are increasing in incidence and mortality. Myocardial dysfunction frequently accompanies severe sepsis and septic shock. Although previously described as a preterminal event, ventricular dysfunction with reduced ejection fraction and biventricular dilatation is present in most patients with severe sepsis and septic shock. In survivors, this depression in cardiac function is reversible over the course of seven to ten days. Even though some prognostic factors have been identified in patients with sepsis-induced myocardial dysfunction, their measurement often includes costly and cumbersome techniques. Thus, there is a need for an inexpensive, simple, rapid and readily available marker to predict mortality in septic shock. At present, a relationship between BNP with myocardial dysfunction in septic shock has not been evaluated. However, growing evidence supports the hypothesis that BNP could be an early predictor of mortality in septic shock. If proven, the hypothesis would have important clinical and public health implications.

One of the most common and life-threatening cardiovascular complications of HIV-infection is severe global left ventricular dysfunction due to primary heart muscle disease. At present, there is no single, cost-effective and reliable method of identifying the highly prevalent HIV-related cardiac dysfunction. Nonetheless, growing evidence supports the hypothesis that brain natriuretic peptide measurement has the potential to detect patients who develop HIV-related cardiomyopathy. If true, this hypothesis would have important clinical and public health implications.

No abstract

Natriuretic peptides, in particular, brain or B-type, are useful for the assessment of patients presenting with dyspnea to the medical office or emergency department. Levels of natriuretic peptides are useful for assessing prognosis of heart failure or coronary syndrome patients. Less is known about serial peptide measurements for guiding treatment strategies in heart failure. The authors review the uses, pitfalls, and practical points for using natriuretic peptides clinically.

The use of Human Immunodeficiency Virus (HIV) protease inhibitors as part of the Highly Active Antiretroviral Therapy (HAART) is associated with atherogenic dyslipoproteinemia, insulin resistance, hypertension and endothelial dysfunction, all of which contribute to premature coronary heart disease. These abnormalities appear to be associated with an increase in cardiovascular events in HIV-infected patients. Beneficial metabolic effects of anti-diabetic agents used in HIV-infected patients have been reported. The thiazolidinediones (TZDs), a new group of antidiabetic drugs, may modulate the proliferative and inflammatory cascades involved in atherosclerosis. Thus, an increasing totality of evidence suggests that TZDs may represent a unique and powerful research tool to find a common denominator underlying the pathophysiology and treatment of the metabolic cardiovascular risk factors associated with HIV infection.

A 70-year-old man presented to the emergency department with chest discomfort, hypotension, and bradycardia. The initial ECG revealed an ST-segment elevation inferoposterior myocardial infarction (MI). The patient was treated with aspirin, atropine, dopamine, unfractionated heparin, and eptifibatide, and was then referred for emergent cardiac catheterization. After temporary pacemaker placement, coronary angiography revealed a subtotal occlusion of the midright coronary artery (RCA) that was associated with a large intracoronary thrombus (Figure 1, left) and TIMI-2 flow. To minimize the possibility of coronary atherothromboembolism and the no-reflow phenomenon, a decision was made to perform a culprit lesion atherothrombectomy using an Export catheter (Medtronic) over a FilterWire distal protection device (Boston Scientific). Two sequential aspirations were performed, resulting in a marked resolution of the thrombus and reduction of the lesion length (Figure 1, middle). Coronary stenting produced a good angiographic result without evidence of the no-reflow phenomenon (Figure 1, right). The catheter aspirate demonstrated 3 visible specimens 3 to 6 mm in diameter. A small amount of debris was noted within the distal protection device. Histopathological analysis of the aspirate revealed a fibrin-rich thrombus along with cholesterol crystals, indicative of a ruptured lipid-rich plaque (Figure 2). The aspirate also demonstrated cellular inflammation, as evidenced by lipid-laden macrophages and a dense neutrophilic infiltrate surrounding the cholesterol crystals. Consistent with a lack of atherothromboembolism, the patient's predischarge echocardiogram revealed a normal ejection fraction of 62% without wall motion abnormalities. This report demonstrates interventional extraction of an acute coronary plaque rupture, the primary event underlying acute myocardial infarction.