Evaluation of pharmacogenetic algorithm for warfarin dose requirements in Japanese patients.

BACKGROUND: Warfarin dosing is difficult to establish because of considerable interindividual variation. Thus, warfarin pharmacogenetics have attracted particular interest in relation to appropriate control of anticoagulation. METHODS AND RESULTS: The 200 eligible subjects were chosen from participants in a hospital cohort. Performance of a pharmacogenetic algorithm recently developed by the International Warfarin Pharmacogenetics Consortium (IWPC) was tested and compared with a clinical algorithm (without genotype data) by calculating the percentage of patients for whom the predicted dose deviated by less than 7 mg/week (1 mg/day) from the actual dose. The pharmacogenetic algorithm accurately identified a significantly (P<0.05) larger proportion of patients to achieve the target international normalized ratio than did the clinical algorithm (68% vs 36% for a low-dose group; and 21% vs 0% for a high-dose group). Also, an increase in warfarin dosage was found to be appropriate for the current status of alcohol drinking (4 mg/week, as against non-drinking) and smoking (3.3 mg/week, as against non-smoking). CONCLUSIONS: The IWPC pharmacogenetic algorithm has clinical application, particularly in identifying Japanese patients who require a low dosage of warfarin and are at greater risk of excessive anticoagulation.

11C-methionine PET of acute myocardial infarction.

UNLABELLED: Tissue uptake of l-[methyl-(11)C]-methionine ((11)C-methionine) has been used to monitor amino acid metabolism and protein synthesis. We examined whether (11)C-methionine was retained in areas of myocardial infarction after successful reperfusion. METHODS: Nine patients with infarction in the left anterior descendent region underwent percutaneous transluminal coronary artery intervention within 24 h and (201)Tl SPECT, (18)F-FDG PET, and (11)C-methionine PET within 2 wk of infarction onset. The standardized uptake values of the infarcted area and of the normal area were measured. RESULTS: The (11)C-methionine images showed increased uptake in the infarcted area, whereas the (201)Tl SPECT and (18)F-FDG PET images showed decreased uptake. The highest accumulation of (11)C-methionine in the infarcted area was observed during the early phase of AMI. CONCLUSION: (11)C-methionine uptake is elevated in infarcted areas and may reflect the early acute phase of damage healing, that is, the initial process of remodeling.

A survival case of acute mitral regurgitation and cardiogenic shock caused by subtotal occlusion of the first diagonal branch.

An 80-year-old woman was admitted with cardiogenic shock; she arrived in a deep coma with systolic blood pressure of 44 mmHg. An electrocardiogram showed ST elevation in I, aVL, V5 and V6, suggesting myocardial infarction in the lateral area of the left ventricle. A chest roentgenogram showed right pulmonary edema without cardiomegaly. Transthoracic and transesophageal echocardiograms revealed severe mitral regurgitation and a flailing anterior mitral valve leaflet, suggesting a ruptured papillary muscle. The patient was initially treated with high-dose dopamine, dobutamine and norepinephrine. Intraaortic balloon pumping was initiated after the patient's condition stabilized. She underwent emergency mitral valve replacement with a prosthetic valve. Complete rupture of the anterior papillary muscle was confirmed. Histological examination revealed necrosis of the anterior papillary muscle with inflammatory changes. She recovered uneventfully. Postoperative coronary angiography demonstrated subtotal occlusion of the first diagonal branch, and left ventriculography demonstrated akinesis of the lateral segment. This was a rare case in which subtotal occlusion of the first diagonal branch caused rupture of an anterior papillary muscle leading to severe mitral regurgitation.