Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes.

Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR > 4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R(2) of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.

Cardiac troponin T, creatine kinase, and its isoform release after successful percutaneous transluminal coronary angioplasty with or without stenting.

BACKGROUND: Cardiac troponin T is a sensitive and specific marker for the detection of minor myocardial injury. However, it has been rarely used to monitor myocardial injury after coronary stenting. The purpose of the study was to measure troponin T after apparently successful percutaneous transluminal coronary angioplasty (PTCA) with or without coronary stenting and to compare its result with serum creatine kinase and its isoform, CKMB. METHODS: The incidence of cardiac troponin T elevation was compared with that of creatine kinase or CKMB in 120 consecutive patients with symptomatic ischemia undergoing visually successful PTCA with (n = 59) or without stenting (n = 61). Troponin T, creatine kinase, and CKMB were measured before, immediately after, and 18 to 24 hours after the procedures were performed. RESULTS: No patient had abnormal troponin T, creatine kinase, or CKMB levels before and immediately after the procedures. Moreover, no patient showed electrocardiographic evidence of myocardial infarction. Troponin T was elevated in 17 patients at 18 to 24 hours after coronary stenting and in eight patients after PTCA. Both creatine kinase and CKMB were elevated in five patients after coronary stenting and in three patients after PTCA. The frequency of abnormal troponin T levels was significantly higher than that of creatine kinase or CKMB after coronary interventions (21% vs 6.7%; p < 0.01), and it was significantly higher after stenting when compared with angioplasty alone (29% vs 13%; p < 0.05). Patients with abnormal troponin T levels were more likely to undergo repeat revascularization than those without (24% vs 6%; p < 0.01). CONCLUSION: Cardiac troponin T is more sensitive than creatine kinase and CKMB in detecting minor myocardial injury after coronary interventions. The incidence of troponin T release is higher in the patients undergoing stent implantation than in patients treated with angioplasty alone.

Cardiac metastasis of hepatocellular carcinoma mimicking pericardial effusion on radionuclide angiocardiography.

A 51-year-old man presented with exertional dyspnea for two months. He had a history of hepatocellular carcinoma that was totally resected three years earlier. Radionuclide angiocardiography disclosed a large photopenic area separating the heart from the liver, and lung blood pools mimicking a large pericardial effusion. Echocardiography and magnetic resonance imaging of the heart, however, showed extensive tumor infiltration of the myocardium of both ventricles. Endomyocardial biopsy confirmed the diagnosis of metastatic hepatocellular carcinoma. There was no evidence of recurrent hepatoma in the liver.