Effect of genetic factors on the interindividual variability of warfarin dosage requirements in Japanese patients after adjusting for renal function.

Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (ß = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and ß = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.

Leptin is essential in maintaining normal vascular compliance independent of body weight.

The adipocytokine leptin centrally regulates body weight by enhancing metabolic rate and signaling satiety, but it also has wide-ranging peripheral effects. Leptin receptors are expressed on vascular smooth muscle cells and have a role in maintaining vascular tone. We investigated the vascular effects of leptin repletion or calorie restriction on leptin-deficient mice (ob/ob) and a leptin antagonist on wild-type (WT) mice. Aortic compliance was assessed by the measurement of pulse wave velocity by noninvasive Doppler; blood pressure was measured by left ventricular catheterization. We found that ob/ob mice have much stiffer aortas than WT mice and that reduction in aortic stiffness was greater in ob/ob mice treated with leptin vs calorie restriction, despite similar weight loss. Interestingly, treating WT mice with a leptin antagonist increases aortic stiffness with no change in weight. Thus, we conclude that leptin is essential for maintaining normal aortic compliance independent of body weight.

[Anatomical variations of Koch's triangle in patients with atrioventricular nodal reentrant tachycardia: usefulness of the left anterior oblique view].

OBJECTIVES: Several anatomical distances of Koch's triangle including the ablation site were measured and correlated with clinical features and slow pathway potentials in patients with atrioventricular nodal reentrant tachycardia to improve the avoidance of complete atrioventricular block. METHODS: Sixty consecutive patients (24 males and 36 females, mean age 47 +/- 12 years) with successfully eliminated atrioventricular nodal reentrat tachycardia were studied. The distances between the His-bundle area and the base of the coronary sinus ostium (Dis HBE-CS) and the distances between the successful ablation site and the base of the CS ostium (Dis SP-CS) were measured in both right anterior oblique and left anterior oblique views, and used to define the dimensions of Koch's triangle. The relationship between the slow pathway potentials at the successful ablation site and anatomical distances was estimated. RESULTS: The Dis HBE-CS in the right anterior oblique view was negatively correlated with patient age (r = -0.759, p < 0.001) and body mass index. In contrast, the Dis HBE-CS in the left anterior oblique view had only weak correlations with patient age and body mass index. The mechanism of the short Dis HBE-CS in the right anterior oblique view in elderly obese patients tended to change the shape of the tricuspid annulus from a circle to an ellipse, compressed by the ascending aorta and diaphragma. The Dis SP-CS in the right anterior oblique view associated with the low frequency potential (Haissaguerre's slow pathway potential) was longer than that associated with the high frequency potential (Jackman's slow pathway potential). CONCLUSIONS: Elderly obese patients had shorter distances between the proximal His-bundle area and the base of the coronary sinus ostium in the right anterior oblique view. In contrast, the Dis HBE-CS in the left anterior oblique view was not so narrow. Therefore, slow pathway ablation can be performed safely without complicated complete atrioventricular block, using both the slow pathway potential guided approach and the anatomical guided approach, especially in the left anterior oblique view.

[Significance of exercise-induced ST segment depression in patients with myocardial infarction involving the left circumflex artery: evaluation by exercise thallium-201 myocardial single photon emission computed tomography].

The significance of exercise-induced ST segment depression in patients with left circumflex artery involvement was investigated by comparing exercise electrocardiography with exercise thallium-201 single photon emission computed tomography(Tl-SPECT) and the wall motion estimated by left ventriculography. Tl-SPECT and exercise electrocardiography were simultaneously performed in 51 patients with left circumflex artery involvement(angina pectoris 30, myocardial infarction 21). In patients with myocardial infarction, exercise-induced ST depression was frequently found in the V2, V3 and V4 leads. In patients with angina pectoris, ST depression was frequently found in the II, III, aVF, V5 and V6 leads. There was no obvious difference in the leads of ST depression in patients with myocardial infarction with ischemia and without ischemia on Tl-SPECT images. In patients with myocardial infarction, the lateral wall motion of the infarcted area evaluated by left ventriculography was more significantly impaired in the patients with ST depression than without ST depression(p < 0.01). Exercise-induced ST depression in the precordial leads possibly reflects wall motion abnormality rather than ischemia in the lateral infarcted myocardium.

[Electrocardiographic findings in pulmonary thromboembolism--comparison with lung perfusion scan and echocardiographic findings].

This study investigated the usefulness of electrocardiography (ECG) in pulmonary thromboembolism (PTE), compared with lung perfusion scan and echocardigraphic findings on evaluation of the severity. We checked ECG findings associated with PTE at hospital admission, with the seven abnormal findings described by Sreeram N, et al. On Lung perfusion scan, severity of perfusion defect was assessed total defect score (TDS), calculated as the sum of the scores for all 18 segment of lung. On echocardiography, severity of right ventricular overload was assessed. The number of the seven ECG abnormal findings and TDS were larger in patients with the right ventricular overload (p < 0.01). The number of the ECG findings was positively correlated with TDS (r = 0.75). The number of abnormal ECG findings in PTE is associated with the severity evaluated by lung perfusion scan and echocardiography.

[Usefulness of early tetrofosmin myocardial SPECT during subacute period to estimate salvaged myocardium in patients with acute myocardial infarction--comparing with tetrofosmin myocardial SPECT during chronic period and evaluating regional wall motion using QGS method].

To evaluate salvaged myocardium of acute myocardial infarction (AMI), we performed rest 99mTc-tetrofosmin (TF) SPECT with rest Tl and Tc-pyrophosphate (PYP) dual SPECT within 10 days after admission in 19 patients with initial AMI, who all were reperfused successfully and without restenosis. TF SPECT was obtained at 15 minutes (E) after tracer injection, 4 hours later (D), and 5 months later (FU). We calculated the regional uptake score (RUS) of infarcted area estimated by Tc-PYP uptake and defined RUS(FU) of TF(FU) as salvaged myocardium, and then regarded RUS/RUS(FU) x 100 (%) as subacute predicted value of salvaged myocardium. Furthermore, we regarded the improvement of wall motion estimated by QGS method as the guidepost of myocardial viability. The subacute predicted value of TF(E) was 85 +/- 25%, which was significantly higher than 61 +/- 28% of Tl and 36 +/- 24% of TF(D) (p < 0.01). Sensitivity and specificity of myocardial viability based on the improvement of wall motion SPECT image were 78% and 73% for Tl, 90% and 87% for TF(E) and 52% and 87% for TF(D). TF myocardial early imaging in subacute period was useful to detect salvaged myocardium.

Biopsy-proven cardiomyopathy in heterozygous Fabry's disease.

A 23-year-old woman with heterozygous Fabry's disease who had acroparesthesia was admitted to hospital for precise examination of the disease before childbearing. She had no cardiac-related symptoms and no abnormality on physical examination. The alpha-galactosidase A activity in her leukocytes was present, but lower than normal. However, the endomyocardial biopsy showed specific changes for Fabry's disease. As Fabry's disease is a rare X-linked recessive inborn error of glycosphingolipid metabolism, heterozygous females are usually asymptomatic, but rarely can be affected as severely as hemizygous males. This is an isolated case of heterozygous Fabry's disease in a female in whom cardiac involvement was detected by endomyocardial biopsy, although she had no cardiac abnormality on physiological examinations. In conclusion, endomyocardial biopsy is useful for evaluation of the cardiac involvement of Fabry's disease even in an asymptomatic case.