[show abstract][hide abstract] ABSTRACT: Currently, β-blockers are used most frequently for the purpose of heart rate (HR) control in patients with atrial fibrillation (AF) in worldwide. Carvedilol is one of common β-blockers and known to be effective for hypertension and heart failure. However, little can be found the information about the HR-lowering effect of carvedilol in patients with AF without heart failure. Therefore, we conducted this study to investigate the effect of carvedilol on HR in 3-minute electrocardiogram (ECG) and total heart beats (THBs) in 24-hour Holter ECG monitoring in patients with persistent or permanent AF.
A total of 13 hypertensive patients (73 ± 12 years, 7 males) with AF and HR 90 bpm or more were enrolled. All patients received carvedilol from 5 mg/day. The dose of drug was titrated every 4 weeks and raised to 10 or 20 mg/day if HR was 80 bpm or more.
Mean HR was decreased from 101.9 ± 13.9 to 85.2 ± 15.2 bpm (P < 0.05) after treatment with carvedilol. THBs were also significantly decreased from 128 to 115 × 1,000/day (P < 0.001). Percent reduction in HR and THBs were 13.9% and 10.7%, respectively. The scores of Atrial Fibrillation Quality of Life Questionnaire (AFQLQ) did not change. Only one patient was required to discontinue carvedilol due to congestive heart failure.
We observed that carvedilol certainly reduced HR in patients with chronic AF. We believe that the effect of carvedilol on the reduction in HR can contribute to the management of AF patients treated with rate-control strategy.
Journal of Clinical Medicine Research 12/2013; 5(6):451-9.
[show abstract][hide abstract] ABSTRACT: Background: Target anticoagulation levels for warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF) are unclear. Methods and Results: Of 7,527 patients with NVAF, 1,002 did not receive warfarin (non-warfarin group), and the remaining patients receiving warfarin were divided into 5 groups based on their baseline international normalized ratio (INR) of prothrombin time (≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0). Patients were followed-up prospectively for 2 years. Primary endpoints were thromboembolic events (cerebral infarction, transient ischemic attack, and systemic embolism), and major hemorrhage requiring hospital admission. During the follow-up period, thromboembolic events occurred in 3.0% of non-warfarin group, but at lower frequencies in the warfarin groups (2.0, 1.3, 1.5, 0.6, and 1.8%/2 years for INR values of ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0059). Major hemorrhage occurred more frequently in warfarin groups (1.5, 1.8, 2.4, 3.3, and 4.1% for INR values ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0041) than in non-warfarin group (0.8%/2 years). These trends were maintained when the analyses were confined to patients aged ≥70 years. Conclusions: An INR of 1.6-2.6 is safe and effective at preventing thromboembolic events in patients with NVAF, particularly patients aged ≥70 years. An INR of 2.6-2.99 is also effective, but associated with a slightly increased risk in major hemorrhage. (UMIN Clinical Trials Registry UMIN000001569).
[show abstract][hide abstract] ABSTRACT: Circadian variations in the QT interval (QT) and QT dispersion are decreased in patients with type 2 diabetes because of cardioneuropathy. Insulin resistance has been recently identified as an independent determinant of QT prolongation in normoglycemic women. However, the relationship between QT prolongation and the degree of insulin resistance as well as circadian variation remains unclear in diabetic patients. This study was designed to assess the relationship between insulin resistance and the circadian variation in QT measurements in patients with type 2 diabetes. In 14 patients with diabetes, QT, corrected QT (QTc), QT dispersion, QTc dispersion, and RR interval (RR) were analyzed using 12-lead Holter monitoring and commercial software. The degree of diurnal variation in each measurement was defined as the amplitude between the maximum and mean values on curves fitted using the mean cosinor method (A_QT, A_QTc, A_QT dispersion, A_QTc dispersion, and A_RR). The cosine curve was fitted to all measured values in each QT measurement and RR for 24 h. Insulin resistance (glucose infusion rate (GIR)) was measured using the euglycemic hyperinsulinemic glucose clamp method. The maximum QT, QTc, QT dispersion, and QTc dispersion were >450 ms. GIR was significantly correlated with A_QT only (r = 0.59, P < 0.05). GIR was not correlated with other variables, and was dependent only on the circadian variation in QT.
[show abstract][hide abstract] ABSTRACT: Background: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. Methods and Results: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25-50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1-10μg·kg(-1)·min(-1) according to the patient's condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. Conclusions: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.
[show abstract][hide abstract] ABSTRACT: Treatment guidelines for atrial fibrillation (AF) used in Western countries describe female gender as a risk factor for thromboembolic events in patients with non-valvular AF (NVAF). The present study aimed to determine impact of gender on prognosis of Japanese NVAF patients. A sub-analysis of 7,406 NVAF patients (mean age, 70 years) who were followed-up prospectively for 2 years was performed using data from the J-RHYTHM registry. The primary endpoints were thromboembolic events, major hemorrhaging, total mortality, and cardiovascular mortality. Compared with male subjects (n = 5,241), females (n = 2,165) were older and displayed higher prevalences of paroxysmal AF, heart failure, and hypertension, but lower prevalences of diabetes, prior cerebral infarction, and coronary artery disease. Male and female patients had mean CHADS2 scores of 1.6 and 1.8, respectively (p <0.001). Warfarin was given to 87% of male patients and 86% of female patients (p = 0.760), and the two genders displayed similar mean international normalized ratio of prothrombin time values at baseline (1.91 vs 1.90, p = 0.756). Multivariate logistic regression analysis indicated that male gender was an independent risk factor for major hemorrhaging (odds ratio, 1.59; 95% confidence interval, 1.05–2.40; p = 0.027) and all-cause mortality (1.78, 1.25–2.55, p <0.002), but not for thromboembolic events (1.24, 0.83–1.86, p = 0.297) or cardiovascular mortality (0.96, 0.56–1.66, p = 0.893). In conclusion, female gender is not a risk factor for thromboembolic events among Japanese NVAF patients that were treated mostly with warfarin. However, male gender is a risk factor for major hemorrhaging and all-cause mortality.
The American journal of cardiology 01/2013; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The prognostic value of heart rate variability (HRV) in patients with cardiac conditions has been investigated for many years. However, the HRV is superior to annual health examinations for predicting the longevity of very elderly residents of long-term care facilities is unknown. Annual health examinations and subsequently ambulatory Holter ECG recording were performed in 2008 for 71 very elderly subjects, who were then followed up for 3 to 48 months. The patients were divided into 2 groups on the basis of whether they were alive (86 ± 14 years, n=37) or deceased (90 ± 16 years, n=34) at end of follow-up. To assess cardiac autonomic function, HRV was obtained with the MemCalc/Chiram software program after Holter ECG. Age, sex, body-mass index, plasma levels of C-reactive protein and albumin, and the low-frequency/high-frequency ratio did not differ between the 2 groups. However, the standard deviation of all NN intervals (SDNN) and the coefficient of variation of RR intervals (CVRR) were higher in living subjects than in deceased subjects (SDNN: 73.2 ± 13.5 milliseconds vs. 53.2 ± 9.8 milliseconds, CVRR: 9.3% ± 1.7% vs. 7.6% ± 1.3%, p<0.05). The relative risks with an SDNN <65 milliseconds was 1.85 (p<0.05) and that with a CVRR <8% was 1.84 (p<0.05). Kaplan Meier analysis showed that SDNN and CVRR were useful markers for the longevity of very elderly subjects. The present data suggest that annual health examination data does not predict longevity, but that HRV does. The modulation of parasympathetic tone in daily activities plays an important role in the longevity of very elderly residents of long-term care facilities.
Journal of Nippon Medical School 01/2013; 80(6):420-5.
[show abstract][hide abstract] ABSTRACT: Atrial fibrillation (AF) is the most common arrhythmia in persons of advanced age, and it is a potent risk factor for cardiogenic ischemic stroke. The overall prevalence of AF is less than 1%, but in people aged 80 years or older the rate is approximately 7–14% in Western countries and 2–3% in Japan. The number of people with AF has been increasing worldwide as the population has aged, and continued increases in the prevalence and incidence of AF are expected with the aging of society. It is predicted that 5–16 million in the United States and more than 1 million in Japan will be affected by 2050. Therefore, AF is one of important diseases that needs to be managed because it is a common disease in aged populations.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Insulin resistance associated with compensatory hyperinsulinemia plays a significant role in the pathogenesis of cardiovascular diseases, including vasospastic angina (VSA). However, the effects of insulin resistance associated with hyperinsulinemia on the long-term prognosis in patients with VSA remain unclear. METHODS: A total of 265 selected patients with VSA and 56 control subjects with atypical chest pain were enrolled in the present study. Patients with VSA had a positive acetylcholine (ACh) provocation test with normal coronary angiograms, and control subjects had a negative ACh test and normal coronary angiograms. A 75-g oral glucose tolerance test was performed, and the plasma glucose and immunoreactive insulin (IRI) levels were measured before, and 30min and 120min (IRI 120) after the 75-g glucose load. RESULTS: During the median follow-up period of 90.0months, thirty-one patients developed cardiac events, including 6 sudden cardiac deaths and 25 readmissions for acute coronary syndrome. Cardiac events occurred in 38.9% of the patients with an IRI 120≥80μU/ml and only 1.6% of the patients with an IRI 120<80μU/ml (log rank 77.220, p<0.001). A multivariate analysis showed that an IRI 120≥80μU/ml (hazard ratio 27.49, 95% confidence interval: 4.66-162.10, p<0.001) was an independent predictor of cardiac events. CONCLUSIONS: These data indicate that insulin resistance associated with compensatory hyperinsulinemia increases the risk of cardiac events in VSA patients.
International journal of cardiology 06/2012; · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: The effects of statin therapy on the production of monocyte pro-inflammatory cytokines, cardiac function and the long-term prognosis in chronic heart failure (CHF) patients with dyslipidemia remain unclear. Methods and Results: A total of 146 CHF patients with a mean left ventricular ejection fraction (LVEF) of 26.9±6.6% were divided into 2 groups based on whether or not statins were included in their treatment: a statin group (n=63) and a no statin group (n=83). Only patients with dyslipidemia were treated with statins. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured at baseline and after 6 months of treatment, and the data expressed as mean±SD (pg·ml(-1)·10(-6) PBMCs). The LVEF in the statin group improved, and the monocyte TNF-α and IL-6 production decreased (respectively, P<0.001), but the LVEF and cytokine production remained unchanged in the no statin group. Multivariate Cox hazard analysis showed that statin therapy (hazard ratio, 0.14; 95% confidence interval: 0.02-0.97, P=0.046) was an independent predictor of cardiac events. Conclusions: Statin therapy attenuates the production of monocyte pro-inflammatory cytokines, and ameliorates the cardiac function and may improve long-term prognosis in CHF patients with dyslipidemia. (Circ J 2012; 76: 2130-2138).
[show abstract][hide abstract] ABSTRACT: BACKGROUNDS: Left ventricular (LV) dyssynchrony reduces LV systolic function in patients with heart failure (HF). However, it remains unknown whether this relationship is independent of impaired LV myocardial perfusion. METHODS AND RESULTS: A total of 105 patients with chronic HF (age 71±13years; 71 men) were enrolled in the present study. (99m)Tc-sestamibi (MIBI) gated myocardial scintigraphy was performed at rest to assess LV myocardial perfusion as evaluated by the total defect score of perfusion Single Photon Emission Computed Tomography images (TDS-MIBI), LV systolic function as evaluated by LV ejection fraction (LVEF), and LV systolic dyssynchrony as evaluated by the maximal difference of time to end systole (MD-TES), which is the time lag between the earliest and the latest end systole among 17 LV segments analyzed with a novel program, "cardioGRAF". The mean±SD (minimum and maximum range) of the MD-TES was 147.8±117.5 (14.0-458.3)ms. The MD-TES was significantly higher in patients with LVEF<45% (199.4±117.6ms) than in those with LVEF≥45% (60.5±41.2ms, p<0.001). In a multiple logistic regression analysis, the MD-TES showed an increased odds ratio for LVEF<45% (2.46 [95% CI; 1.51-4.01] per increment in decile of MD-TES rank, p<0.001), after adjusting for the TDS-MIBI, history of myocardial infarction, and other potential confounders. CONCLUSIONS: LV dyssynchrony is a significant determinant of LV systolic dysfunction in patients with HF, and this relationship is independent of impaired LV myocardial perfusion and history of myocardial infarction.
International journal of cardiology 03/2012; · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aim: As 2 years have passed since its implementation, and we have received several comments regarding our original article, we report the recent developments of end-of-life (EOL) care in a special elderly (SE) nursing home and describe the role of doctors. Participants: A total of 7 female EOL care patients (age, 101.5±4 years) in a special elderly home and 130 patients (98 years, 42 men, 88 women; age, 87±6.5 years) receiving palliative therapy in a hospital. Results: Four of the 7 EOL care patients died after an average of 480±297 days within our EOL care system, while 3 patients spent an average of 805±662 days in our SE home. Among the hospitalized patients, 93 (71.5%; 27 men and 66 women; age, 86.7±10 years) were able to be discharged to our facility, whereas 37 (28.5%; 15 men, 22 women; age, 86.4±11 years) died during hospital care. A number of patients who could discharge had a greater incidence of gastrointestinal disorders than congestive heart failure (p<0.05). Among 15 patients (≥98 years) who could not enter EOL care because of family problems, 12 were hospitalized and 9 died before discharge. This number was significantly greater than the number who died before discharge and who were <98 years (p<0.05). One patient (aged 103 years) who had a solid breast tumor successfully underwent surgery and was discharged after 3 days of admission, but she died within 90 days of EOL. The death rates in our nursing home were significantly lower than the average death rate in other facilities (15.3% vs. 37.2%, p<0.01). Conclusion: Patients of over 98 years old did not live longer, despite hospitalized care; however, the number of patients (28%) who were less than 98 years could be discharged and were alive was significantly less than centenarians (p<0.05). Doctors in nursing homes should provide communication support for nursing homes and hospitals after providing medical education for care workers.
Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 01/2012; 49(3):336-43.
[show abstract][hide abstract] ABSTRACT: Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for stroke. For more than 60 years, warfarin has been the only approved anticoagulant for prevention of stroke in patients with AF. Although highly effective, it has many limitations that make its use difficult. Therefore, several novel anticoagulants are under development to overcome the limitations of warfarin, and some of these have entered phase III clinical trials. Dabigatran is an oral, reversible direct thrombin inhibitor approved in Europe and in several other countries for the prevention of venous thromboembolism after elective knee and hip replacement surgery. It has also been approved in the United States and Japan for the prevention of stroke and systemic embolism in patients with nonvalvular AF. In this review, the mechanism of action and pharmacological properties of new anticoagulants are described in detail, and the correct use of dabigatran in clinical practice is discussed.
[show abstract][hide abstract] ABSTRACT: Nitrates have been widely used as anti-ischemic drugs in patients with vasospastic angina (VSA). However, the effect of long-term nitrate treatment on cardiac events in VSA patients remains unclear.
Two-hundred and thirty-one patients with VSA who had not been receiving any antiischemic drugs, including calcium channel blockers (CCBs), nitrates, nicorandil, or any combination of these medications were prospectively enrolled in the present study. All patients had a positive acetylcholine provocation test with normal coronary angiograms, and they received CCBs after enrollment. They were divided into 2 groups based on whether nitrates were included in the treatment: a nitrate group (n=86) and a without nitrate group (n=145). The baseline clinical characteristics and frequency of anginal attacks within 48h before enrollment were similar between the 2 groups. With a median follow-up period of 70.5 months, 29 patients developed cardiac events, including 7 sudden cardiac deaths and 22 re-admissions for acute coronary syndrome. Cardiac events occurred in 19.8% of the nitrate group and in only 8.3% of the patients who were not taking nitrates (P=0.015). In a multivariate analysis, long-term nitrate treatment (hazard ratio 5.18, 95% confidence interval: 1.69-15.89, P=0.004) was an independent predictor of cardiac events.
These data indicate that long-term nitrate treatment in addition to CCBs might not reduce cardiac events in VSA patients.
[show abstract][hide abstract] ABSTRACT: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors and an increased risk of cardiovascular events. The carotid intima-media thickness (CIMT) is correlated with coronary and carotid atherosclerosis, and is a significant predictor of cardiovascular events. Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. TF plays important roles in both thrombosis and atherosclerosis. No study has investigated the relationship between monocyte TF activity and CIMT in MS patients.
Peripheral blood mononuclear cells (PBMCs) were collected from 39 normal subjects and 110 patients with MS. The procoagulant activity (PCA) in monocytes was measured using a one-stage clotting assay and is expressed as the mean±SD (mU TF/10(6) PBMCs).
The PCA in monocytes in MS patients was significantly higher than in normal subjects (86.2 ±69.5 vs. 52.4±9.9 mU TF/10(6) PBMCs, p < 0.001). In multivariate analysis, patient age (β coefficient= 0.373, p < 0.001), high-density lipoprotein cholesterol (β coefficient=-0.307, p = 0.001) and PCA (β coefficient= 0.422, p =0.002) were each significantly and independently associated with CIMT.
These data indicate that the upregulation of monocyte TF activity is significantly associated with CIMT in MS patients.
Journal of atherosclerosis and thrombosis 04/2011; 18(6):475-86. · 2.93 Impact Factor
[show abstract][hide abstract] ABSTRACT: Underuse and an inadequate range for the international normalized ratio (INR) for warfarin use are still problems in the management of the patients with atrial fibrillation (AF) in Japan.
From January to July 2009, a total of 7,937 AF patients [5,468 men (68.6 ± 10.0 years) and 2,469 women (72.2 ± 9.0 years)] were registered from 158 institutions for the J-RHYTHM Registry. Overall, 34.2% of the patients were over the age of 75. The associated cardiovascular diagnoses were hypertension in 59.1%, coronary artery disease in 10.1%, cardiomyopathy in 8.3%, valvular heart disease in 13.7% and artificial cardiac valves in 3.1% of the patients. The type of AF was paroxysmal in 37.1%, persistent in 14.4%, and permanent in 48.5%. Overall, 87.3% of patients were taking warfarin (2.9 ± 1.2mg/day), of whom 66.0% had an INR between 1.6 and 2.6, and 35.4% were in the INR range from 2.0 to 3.0 at the time of registration. Aspirin was prescribed in 22.3% of cases. The CHADS2 score was 0 in 15.7% of patients, 1 in 34.0%, and ≥ 2 in 50.3%.
At present, warfarin is used extensively in patients with AF whose stroke risk is relatively low (ie, in Japan) and half of them had CHADS2 scores of 0 to 1 (UMIN Clinical Trials Registry UMIN000001569).
[show abstract][hide abstract] ABSTRACT: Proinflammatory cytokine responses might occur in elderly individuals with cardiovascular (CV) disease, cerebro-vascular (CVA) disease, and/or pulmonary disease (PD). Spiritual activation is an important coping mechanism, since psychiatric depression is an important risk factor for these individuals. Thirty-three very elderly individuals (87 ± 8 years) with previous CVD, CVA and/or PD participated in weekly 30 minute sermons by chaplains for over 20 months of chaplain liturgy (CL group). All underwent Holter ECG during the procedures and cardiac autonomic activities were assessed by maximum entropy analysis. Plasma IL-10 and IL-6 levels were compared with 26 age-matched (85 ± 10 years) individuals who did not participate in these activities (non-CL group). Both high frequency (HF) and pNN50 of heart rate variability (HRV) were higher in the CL group than in the non-CL group (HF, 190 ± 55 versus 92 ± 43 nu, P < 0.05; pNN50, 10.5 ± 16% versus 3.6 ± 3.8%, P < 0.05), whereas LF/HF was lower (1.4 ± 1.5 versus 2.2 ± 2.8, P < 0.05). Levels of IL-10/IL-6 were higher in the CL group (3.96 ± 5.0 versus 1.79 ± 1.6, P < 0.05). Hospitalization rates due to CVD and/or PD were lower in the CL group than in the non-CL group (4/33 versus 11/26, P < 0.05). We conclude that spiritual activation can modify proinflammatory cytokines and suppress CVD, CVA and/or PD via vagal modifications. Spiritual activation might be helpful for health in these very elderly individuals.
International Heart Journal 01/2011; 52(5):299-303. · 1.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: Variant angina is a form of angina pectoris that shows transient ST-segment elevation on electrocardiogram during an attack of chest pain. Ischemic episodes of variant angina show circadian variation and often occur at rest from midnight to early morning. Ischemic episodes also occur during mild exercise in the early morning. However, they are not usually induced by strenuous exercise in the afternoon. Other important clinical features of variant angina include the high frequency of asymptomatic ischemic episodes and the syncope that sometimes occur during the ischemic episodes. Syncope is due to severe arrhythmias, including ventricular tachycardia, ventricular fibrillation, and high-degree atrioventricular block. Coronary artery spasm is the mechanism of ischemic episodes in variant angina. The incidence of coronary artery spasm shows a racial difference and is higher in Japanese than in Caucasians. Coronary arteriograms are normal or near-normal in most Japanese patients with variant angina. Deficient basal release of nitric oxide (NO) due to endothelial dysfunction, and enhanced vascular smooth muscle contractility with the involvement of the Rho/Rho-kinase pathway are reported to play important roles in the pathogenesis of coronary artery spasm. Other precipitating factors of coronary artery spasm include imbalance in autonomic nervous activity, increased oxidative stress, chronic low-grade inflammation, magnesium deficiency, and genetic susceptibility. The genetic risk factors associated with coronary artery spasm include gene polymorphisms of endothelial NO synthase (NOS), paraoxonase, and other genes. Calcium channel blockers are extremely effective in preventing coronary spasm. The long-acting nitrate, nicorandil, and Rho-kinase inhibitor are also useful for inhibiting coronary artery spasm. Because variant angina can lead to acute myocardial infarction, fatal arrhythmias, and sudden death, early treatment is important. The prognosis of patients with variant angina is favorable, if early complications can be overcome. However, because coronary artery spasm cannot be suppressed in some patients, even with multiple medications, medications to suppress intractable coronary artery spasm must be developed.
Journal of Nippon Medical School 01/2011; 78(1):4-12.