Tadahisa Uesugi

Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia.

Background: Heart-rate (HR) variability is an important predictor of mortality in patients with heart disease. We examined the effects of cilostazol, a quinolinone derivative, on HR and HR variability in patients with chronic atrial fibrillation associated with bradycardia episodes. Patients and Methods: Thirteen patients with chronic atrial fibrillation associated with bra dycardia episodes (minimal HR <40/min and/or pauses, ie, episodes with an RR interval > 2.5 sec) received cilostazol (100 or 200 mg/day) orally for at least 2 months and 24-hour Holter electrocardiography was performed before and after the start of cilostazol administration. Results: Minimal HR was significantly increased, by an average of 14 beats/min (bpm), at 3.3 ± 0.8 weeks (mean ± SD) after the start of cilostazol treatment. The number of pauses was significantly decreased. As a consequence, mean HR was increased by an average of 18 bpm. Maximal HR was also increased by an average of 19 bpm. The circadian variation of the HR, determined by cosine fitting, was not changed by cilostazol treatment. The time-domain HR variabilities, ie, the SD of the mean RR interval and the SD of the 5-minute mean RR intervals, were also unchanged. New York Heart Association functional class was signifi cantly improved and the plasma atrial natriuretic polypeptide level was significantly de creased after the initiation of cilostazol treatment. Conclusion: Cilostazol improves the slow HR episodes associated with chronic atrial fibril lation and maintains the HR circadian variation and time-domain variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with chronic atrial fibrillation.

Relationship between activin A level and infarct size in patients with acute myocardial infarction undergoing successful primary coronary intervention.

BACKGROUND Activin A, a member of the transforming growth factor-beta cytokine family, has been suggested to have a role in inflammation. We examined the serum level of activin A in patients with acute myocardial infarction (AMI) undergoing successful primary percutaneous coronary intervention (PCI). METHODS The subjects were 30 AMI patients, 20 stable angina pectoris (AP) patients and 20 normal subjects. The serum levels of activin A in AMI patients were measured before PCI and on days 1, 2, 7, and 14. RESULTS Activin A levels before PCI in AMI patients (557+/-255 pg/ml) showed a significantly higher value than those in AP patients (364+/-159 pg/ml) and control subjects (316+/-144 pg/ml). Increased serum activin A level before PCI was decreased on day 2, and then gradually re-elevated on days 7 and 14. The serum activin A level before PCI was correlated with log-transformed peak creatine kinase (CK) as a surrogate of infarct size (r=0.48, p=0.008). Stepwise multiple regression analysis demonstrated that the serum activin A level before PCI was an independent predictor of peak CK. CONCLUSIONS The serum activin A level, increased in AMI, was positively correlated with peak CK and CK-MB levels which are measures of infarction size.

Exponential-exponential cosine fitting of blood pressure decay induced by a long-acting calcium blocker, amlodipine, using home blood pressure measurement

Blood pressure (BP) decay data obtained from home BP measurements in six patients with uncomplicated essential hypertension treated with a calcium blocker, amlodipine, were fitted to an exponential–exponential cosine function to determine the characteristic BP‐lowering effects of amlodipine. An exponential–exponential cosine function fitted the morning and night systolic BP (sBP) decay data better than a simple exponential function. From the coefficients of the equation, the estimated BP lowering, time constant for BP decay and BP oscillation induced by amlodipine for morning and night sBP were approximately 23 and 25 mmHg, 10 and 6 days, and 12 and 12 mmHg, respectively. Diastolic BP showed a similar fitting though the fitting was weaker. The fitting results indicate that the BP decay, especially the sBP decay, induced by amlodipine occurred in an oscillative fashion, and the present analysis using home BP data may provide clinically useful information about the characteristic effects of amlodipine.

Circulating white blood cell count correlates with left ventricular indices independently of the extent of risk area for myocardial infarction after successful reperfusion.

Objective — To test the hypothesis that the circulating white blood cell (WBC) and neutrophil counts are related to left ventricular (LV) indices in patients with the same risk area for acute myocardial infarction (AMI), we examined 100 consecutive AMI patients who had the culprit lesion at segment 6 according to the American Heart Association classification and who underwent successful direct coronary angioplasty. Methods and results — The LV ejection fraction (LVEF), end-systolic volume (LVESVI) and end-diastolic volume index (LVEDVI) were obtained by left ventriculography performed 4 weeks after AMI onset. Univariate analysis disclosed that the counts of WBC and neutrophils on admission, and the maximal WBC count correlated negatively with LVEF (r = –0.46, p < 0.001; r = –0.54, p < 0.001 and r = –0.40, p < 0.001, respectively) and positively with LVESVI (r = 0.43, p < 0.001; r = 0.55, p < 0.001, and r = 0.30, p < 0.01, respectively). The counts of WBC and neutrophils on admission also correlated with LVEDVI (r = 0.28, p < 0.01 and r = 0.41, p < 0.001, respectively). Multivariate analysis with other clinical and angiographic factors revealed that the counts of WBC and neutrophils on admission correlated with LVEF (partial correlation coefficient, r = –0.37, p < 0.001 and r = –0.52, p < 0.001, respectively), with LVESVI (r = 0.34, p < 0.01 and r = 0.56, p < 0.001, respectively) and with LVEDVI (r = 0.28, p < 0.01 and r = 0.44, p < 0.001, respectively). The maximal WBC count also correlated with LVEF and LVESVI (r = –0.40, p < 0.001 and r = 0.21, p < 0.05, respectively). Conclusion — The present study revealed that the circulating WBC count correlated with function and volume of the successfully reperfused LV after AMI in patients with the same risk area for AMI, indicating that the WBC count needs to be taken into consideration as an independent factor affecting the LV indices.

Effects of Cilostazol on Heart Rate and Its Variability in Patients with Sick Sinus Syndrome

ObjectiveHeart rate (HR) variability is an important factor for the prognosis of heart disease. We examined the effects of cilostazol, a quinolone derivative, on HR and HR variability in patients with sick sinus syndrome.DesignNon-blind sequential single-group study.Patients12 patients, aged 53 to 84 years, with type I or II sick sinus syndrome classified according to the Rubenstein system.MethodsPatients received cilostazol (100 or 200 mg/day) orally for at least 2 months, and 24-hour ambulatory electrocardiogram monitoring was performed before and after the start of cilostazol administration. Plasma atrial natriuretic polypeptide (ANP) levels and cardiothoracic ratio were also measured as markers of heart failure. Twelve age- and gender-matched volunteers were used for control measurements of HR variability.ResultsThe mean HR and minimum HR were significantly increased, by an average of 15 and 10 beats/min, respectively, at 8.6 ± 2.5 weeks (mean ± SD) after the start of cilostazol treatment. The number of pauses (defined as an RR interval >2.5 sec) was significantly decreased. The circadian variation of HR, determined by cosine fitting, was increased by cilostazol treatment and was not different from that of the controls. The time-domain and frequency-domain variability of HR were changed to within or closer to within the control ranges. Plasma ANP level and cardiothoracic ratio were significantly decreased after the initiation of cilostazol treatment.ConclusionCilostazol improved the slow HR in patients with sick sinus syndrome and ameliorated the HR variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with sick sinus syndrome.

Effect of Intensive and Standard Pitavastatin Treatment With or Without Eicosapentaenoic Acid on Progression of Coronary Artery Calcification Over 12 Months ― Prospective Multicenter Study ―

BACKGROUND The effect of lipid-lowering agents on progression of coronary artery calcification (CAC) remains unclear. We evaluated the effects of pitavastatin 2 mg/day (PIT2), pitavastatin 4 mg/day (PIT4), and PIT2 combined with eicosapentaenoic acid (PIT2+EPA) on CAC progression.Methods and Results:This prospective multicenter study in Japan included patients with an Agatston score of 1-999, hypercholesterolemia, and no evidence of cardiovascular disease. Patients were allocated into PIT2, PIT4, or PIT2+EPA groups. The primary outcome was the annual percent change in Agatston score in all patients. In total, 156 patients who had multi-detector row computed tomography without any artifacts were included in the primary analysis. Pitavastatin did not significantly reduce the annual progression rate of the Agatston score (40%; 95% CI: 19-61%). The annual progression rate of Agatston score in the PIT2 group was not significantly different from that in the PIT4 group (34% vs. 42%, respectively; P=0.88) or the PIT2+EPA group (34% vs. 44%, respectively; P=0.80). On post-hoc analysis the baseline ratio of low- to high-density lipoprotein cholesterol was a significant predictor of non-progression of Agatston score by pitavastatin (OR, 2.17; 95% CI: 1.10-44.12; P=0.02). CONCLUSIONS Pitavastatin does not attenuate progression of CAC. Intensive pitavastatin treatment and standard treatment with EPA does not reduce progression of CAC compared with standard treatment.

EFFECTS OF A DIRECT RENNIN INHIBITOR OR A DIURETIC ADDED ON AN ANGIOTENSIN II RECEPTOR BLOCKER ON CENTRAL AORTIC PRESSURE IN HYPERTENSIVE PATIENTS (ALEA STUDY)

To achieve the target blood pressure recommended by the latest guidelines, multiple antihypertensive drugs are needed in most patients. Furthermore, recent studies showed that central aortic pressure is closely associated with target organ damages. We compared the effects of a direct rennin