Circulation
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The prognosis and functional capacity of patients with pulmonary arterial hypertension (PAH) is poor, and there is a need for safe, effective, inexpensive oral treatments. A single dose of sildenafil, an oral phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown. ⋯ This small pilot study suggests that long-term sildenafil therapy might be a safe and effective treatment for PAH. At a monthly cost of 492 dollars Canadian, sildenafil is more affordable than most approved PAH therapies. A large multicenter trial is indicated to directly compare sildenafil with existing PAH treatments.
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Lepirudin (Refludan) is a hirudin derivative. It is a direct thrombin inhibitor obtained by recombinant technology from the medicinal leech and is approved for treatment of heparin-induced thrombocytopenia complicated by thrombosis. Because 3 cases of fatal anaphylaxis possibly associated with use of lepirudin have been reported, we initiated an investigation of putative lepirudin-associated anaphylaxis. ⋯ Lepirudin can cause fatal anaphylaxis, particularly in patients who are treated within 3 months of a previous exposure. The overall risk/benefit assessment of lepirudin as a treatment for heparin-induced thrombocytopenia remains favorable.
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Heart rate-corrected QT interval (QTc) is the traditional method of assessing the duration of repolarization. Prolonged heart rate-corrected QT interval is associated with higher risk of mortality in patients with coronary heart disease (CHD) and in the general population. However, the QTc is typically not evaluated when QRS duration is > or =120 ms, because increased QRS duration (QRSd) contributes to QT interval prolongation. In these circumstances, the JT interval has been proposed as a more valid way to assess ventricular repolarization. ⋯ The JTc is a simple measurement that is a significant independent predictor of incident CHD events in men with wide QRS complex.