Acute decompensated heart failure (ADHF) is a major public health problem throughout the world and its importance is continuing to grow. This article reviews the epidemiology of ADHF and the profile of patients suffering from this condition. It describes factors used in assessing prognosis and presents treatment options. Although no currently available treatments have been shown to favorably affect long-term outcomes, there are a variety of strategies and approaches to management that are expected to reduce morbidity and mortality following discharge after ADHF hospitalization. In particular, the clinician is alerted to the need to identify factors that trigger decompensation as well as to optimize treatments for chronic heart failure. The importance of the transition from hospital to the outpatient setting is described. Particular attention should be focused on providing health education to the patient and their family at an appropriate level of medical literacy as well as ensuring early follow-up evaluation after hospital discharge. (Circ J 2012; 76: 532-543)

View full abstract

Cardiac computed tomography (CT) has evolved rapidly over the last decade into a reliable imaging modality for the non-invasive assessment of coronary artery disease. With the advancement in multi-detector CT technology, there has developed an increasing body of evidence that suggests that the role of cardiac CT can be extended to include functional assessment of the myocardium not only at rest but also during stress. Simultaneous anatomical and functional assessment approaches will have a number of advantages such as evaluation of the transmural extent of myocardial perfusion defects (including small subendocardial perfusion defects), reduced risk associated with multiple sources of radiation, and short image acquisition time. Although initial results hold some promise, CT myocardial perfusion imaging is a modality in the early stages of development and further work and studies are required to define, validate, and optimize this technique. This review will provide an overview of this novel perfusion imaging method, its underlying principles, evolution, limitations and future directions. (Circ J 2012; 76: 544-552)

View full abstract

The devastating Great East Japan Earthquake, which was 9.0 on the Richter scale, occurred on March 11, 2011. Japan experienced the Great Hanshin-Awaji Earthquake 16 years ago, and I was working at the epicenter, and reported the characteristics of the earthquake-associated cardiovascular risk and high blood pressure (BP) found during the continuous practice and clinical studies of Tsuna Medical Association before and after the quake. A major disaster increases thrombophilic tendency and BP, both of which trigger disaster-induced cardiovascular events such as stroke, cardiac events, etc. The high salt intake and the increased salt sensitivity caused by disrupted circadian rhythms are the 2 major leading causes of disaster hypertension (HT) through neurohumoral activation under stressful conditions. To better assess and reduce the risks for disaster-associated cardiovascular events, we introduced the web-based Disaster Cardiovascular Prevention (DCAP) network (which consists of DCAP risk and prevention score assessment, and self-measured BP monitoring at both the shelter and the home) to the survivors of the 2011 disaster, and frequently found newly developed HT. Here I review the recent evidence, possible mechanism and the management of "disaster HT" for effective prevention of disaster-induced cardiovascular events. (Circ J 2012; 76: 553-562)

View full abstract

Acute hyperglycemia is a common feature during the early phase after acute myocardial infarction (AMI), regardless of diabetes status. Numerous studies have demonstrated that patients with AMI and hyperglycemia on admission have high rates of mortality. It has been reported that there is a linear positive relation between admission blood glucose levels and mortality after AMI. However, recent studies showed that the relationship is U-shaped in patients with a history of diabetes. Diabetic patients with moderate hyperglycemia (glucose 9-11mmol/L) had the lowest mortality and not only severe hyperglycemia (glucose ≥11mmol/L) but also euglycemia (glucose <7mmol/L) was associated with higher mortality. Although it has been debated whether acute hyperglycemia is causally related to adverse outcomes after AMI or is simply an epiphenomenon of severely damaged myocardium, multiple physiological studies have demonstrated that hyperglycemia has a direct detrimental effect on ischemic myocardium through several mechanisms, including oxidative stress, inflammation, apoptosis, endothelial dysfunction, hypercoagulation, platelet aggregation and impairment of ischemic preconditioning. Current guidelines recommend the use of an insulin-based regimen to achieve and maintain glucose levels <10.0mmol/dl, and emphasize the avoidance of hypoglycemia. However, the optimal management goal of glucose levels for patients with acute hyperglycemia remains uncertain. Further studies are warranted into the appropriate management in patients with AMI and acute hyperglycemia. (Circ J 2012; 76: 563-571)

View full abstract

The evolution of 3-dimensional (D) mapping systems has contributed to improved procedures for ablation of complex tachyarrhythmia in terms of providing detailed anatomical information along with the ability to integrate with pre-acquired computed tomography/magnetic resonance imaging/intracardiac echocardiography images, reducing the radiation exposure, and producing activation and substrate maps. 3-D mapping systems are categorized as magnetic based vs. impedance based according to the catheter location technology, and are also classified as contact based vs. non-contact based according to the data collection technology. Contact-based mapping systems are used widely, in which a series of electrograms is taken sequentially in contact with the heart, thus requiring a relatively stable and sustained arrhythmia to create an activation map. Non-contact mapping systems, however, allow a beat-to-beat analysis of the activation even in non-sustained, polymorphic, or hemodynamically intolerant tachycardia. In this article, the clinical utility of 3-D mapping systems is discussed based on the literature and on experience, with particular emphasis on the non-contact mapping system. (Circ J 2012; 76: 572-581)

View full abstract

Background: Although low atrial septal (LAS) pacing may prevent atrial tachyarrhythmias in selected patients, far-field R-wave (FFRW) sensing in this region seems more likely than in the right atrial appendage. Methods and Results: We compared the clinical characteristics and prevalence of FFRW sensing in 31 recipients (mean age, 74±10 years) of dual-chamber pacemakers, randomly assigned to 10.0mm (n=15) vs. 1.1mm (n=16) tip-ring electrode spacing of bipolar atrial leads implanted in the LAS for management of bradyarrhythmias. The pacemakers were programmed to DDD mode with backup rates at 50-60beats/min. FFRW sensing was measured with atrial sensitivity set at 0.1mV, and increased in 0.1mV steps. Predictors of FFRW sensing were examined by multiple variable regression analysis, and hazard ratios (HR) and confidence intervals (CI) were calculated. At atrial sensitivities of 0.1 and 0.5mV, FFRW was sensed in 24 (77%) and 9 (29%) patients, respectively. A 10.0-mm tip-ring electrode spacing of the atrial lead (HR 10.3; 95%CI 1.0-102.7; P=0.047), and presence of left ventricular hypertrophy (LVH) on 12-lead ECG (HR 14.5, 95%CI 1.2-180.0; P=0.037) were independent predictors of FFRW sensing. Conclusions: The prevalence of FFRW sensing in the LAS region was high. A narrow spacing of the tip-ring electrodes is recommended in the LAS, particularly in the presence of LVH on ECG. (Circ J 2012; 76: 598-606)

View full abstract

Background: Although various kinds of cardiovascular risk factors have been reported to be associated with atrial fibrillation (AF), the relationship between serum uric acid level and AF has not been fully examined. Methods and Results: Data were collected from a single hospital-based cohort in the Shinken Database 2004-2008 (n=11,123), and consisted of serum uric acid level for 7,155 patients. The association between serum uric acid level and AF prevalence was evaluated on logistic regression. Uric acid significantly increased the crude AF prevalence in both men and women (both, P<0.001). The odds ratio (OR) and 95% confidence interval (95%CI) in the highest tertile compared with the lowest one were 3.368 (2.478-4.578) and 1.408 (1.169-1.695) in women and men, respectively. Uric acid was also significantly associated with other various cardiovascular risk factors for AF. Even after the multivariate model was adjusted using these variables, the effect of uric acid on AF was independent in women (OR, 1.888; 95%CI: 1.278-2.790), but not in men. Conclusions: Reflecting the composite of various cardiovascular risk factors, serum uric acid level was apparently associated with AF prevalence. The independent association in women might imply some sex-specific mechanisms. The results should be confirmed in prospective studies. (Circ J 2012; 76: 607-611)

View full abstract

Background: Atrial fibrillation (AF) is the most common supraventricular arrhythmia, often occurring during hemodialysis (HD). Prolongation of the total filtered P-wave duration (PWD) and reduction of the root mean square voltages for the last 20ms of the P wave (RMS20) on a P-wave signal-averaged electrocardiogram (P-SAECG) are predictors of AF. We investigated whether HD induces alterations of P-SAECG, and determined the influential factors. Methods and Results: Thirty-three end-stage kidney disease patients (66.7±12.6 years, 23 males) undergoing maintenance HD were enrolled in this study. Digital ambulatory P-SAECG monitoring and laboratory examination of serum proteins and ions were carried out before, during, and after the HD sessions. Data were analyzed by multiple regression analysis. PWD was significantly prolonged, and RMS20 significantly reduced, during HD. These values recovered after completion of HD. Multiple regression analysis showed that prolongation of PWD significantly correlated with HD duration and the rate of removal of body fluid. On the other hand, RMS20 significantly correlated with HD duration and blood urea nitrogen variation. Conclusions: HD resulted in prolongation of PWD and reduction of RMS20, indicating the vulnerability of HD patients to AF. These P-SAECG changes correlated with HD duration and the rate of removal of the body fluid. These findings underline the importance of the control of dialysis variables in the prevention of atrial arrhythmias following HD. (Circ J 2012; 76: 612-617)

View full abstract

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with an increased risk of sudden cardiac death (SCD). Risk stratification of ARVC/D patients, however, remains an unresolved issue. In this study we investigated whether heart rate variability (HRV) can be helpful in identifying ARVC/D patients with increased risk of arrhythmic events. Methods and Results: We studied 30 consecutive patients (17 males; 45.4±18 years) with ARVC/D, diagnosed according to guideline criteria; 15 patients (50%) had received an implantable cardioverter defibrillator (ICD) for primary SCD prevention. HRV was assessed on 24-h ECG Holter monitoring. The primary endpoint was the occurrence of major arrhythmic events (SCD, sustained ventricular tachycardia (VT), ICD therapy for sustained VT or ventricular fibrillation (VF)). During the follow-up period (19±7 months), no deaths occurred, but 5 patients (17%) experienced arrhythmic events (4 VTs and 1 VF, all in the ICD group). All HRV parameters were significantly lower in patients with, compared with those without, arrhythmic events. Low-frequency amplitude was the most significant HRV variable associated with arrhythmic events in univariate Cox regression analysis (P=0.017), and was the only significant predictor of arrhythmic events in multivariable regression analysis (hazard ratio 0.88, P=0.047), together with unexplained syncope (hazard ratio 16.1, P=0.039). Conclusions: Our data show that among ARVC/D patients HRV analysis might be helpful in identifying those with increased risk of major arrhythmic events. (Circ J 2012; 76: 618-623)

View full abstract

Background: Limited information is available on the ventricular fibrillation (VF) spectrum in Brugada syndrome (BS) patients. We clarified differences in the VF cycle length (CL) using fast-Fourier transformation (FFT) analysis in symptomatic and asymptomatic BS patients. Methods and Results: VF was induced by pacing from the right ventricular (RV) apex and/or RV outflow tract (RVOT) for >8s. A 4096-point FFT analysis of results from 28 male BS patients (51.1±13.7 years old) was performed. Dominant frequency (DF) from phases 1 (4s) to 6 was obtained at 2-s intervals. The average DF from surface and intracardiac electrograms (ECG: DF_ECG; ICE: DF_ICE,, respectively) was compared between symptomatic and asymptomatic patients. Symptomatic patients had a significantly shorter effective refractory period at a CL of 600ms at the RVOT than asymptomatic patients. DF_ECG significantly increased with phase (5.64±0.32Hz in phase 1 to 6.16±0.52Hz in phase 6) and was significantly higher in symptomatic patients than in asymptomatic patients. DF_ICE had the same characteristics as DF_ECG. Conclusions: Induced VF in BS patients can be characterized using FFT analysis. Our data support the hypothesis that symptomatic patients have a significantly shorter VF CL than asymptomatic patients. (Circ J 2012; 76: 624-633)

View full abstract

Background: Patients undergoing coronary stenting during acute coronary syndrome (ACS) are exposed to a higher risk of stent thrombosis (ST) than those undergoing elective stenting. Few studies have aimed to identify ST incidence and predictors in this specific population. Methods and Results: This single-center study enrolled 611 consecutive Tunisian patients with ACS who underwent coronary stenting with bare metal stents (BMS). The incidence of ARC (Academic Research Consortium) definite ST throughout a median 16-month follow-up period was 3.5%; it was 9.2% in patients with ST-elevation myocardial infarction (STEMI) who underwent an emergency percutaneous coronary intervention (PCI). Independent predictors were fever during PCI (hazard ratio (HR) 5.19; 95% confidence interval (95%CI) 1.69-15.95, P=0.004); premature cessation of clopidogrel (HR 2.66; 95%CI 1.02-6.97, P=0.046), resumption of smoking (after PCI) (HR 4.41; 95%CI 1.58-12.27, P=0.005), primary PCI (HR 5.02; 95%CI 1.57-16.01, P=0.006), rescue PCI (HR 6.33; 95%CI 2.08-19.34, P=0.001), reference vessel diameter <2.8mm (HR 6.96; 95%CI 2.06-23.56, P=0.002), TIMI flow grade before PCI <2 (HR 11.51; 95%CI 2.76-48.06, P=0.001) and a visible thrombus (HR 3.57; 95%CI 1.1-11.12, P=0.028). Conclusions: The incidence of ST in ACS patients was higher than classically described. Clopidogrel discontinuation and resumption of smoking are involved. Efforts should be made to improve patient education and secondary prevention. (Circ J 2012; 76: 634-640)

View full abstract

Background: Diverse pharmacological effects of anti-platelet thienopyridines due to individual differences in metabolism have been reported. However, an association between on-treatment platelet reactivity and adverse ischemic events after drug-eluting stent (DES) implantation in Japanese patients has not been fully elucidated. Methods and Results: A total of 450 consecutive patients on dual anti-platelet therapy (aspirin and ticlopidine) with stable angina who underwent DES implantation were enrolled. Adenosine diphosphate (ADP)-induced platelet aggregation was measured before DES implantation using the screen filtration pressure method. The ADP concentration necessary for 50% aggregation was designated as the platelet aggregation threshold index (PATI). A composite primary endpoint of cardiac death, myocardial infarction, target lesion revascularization (TLR), and stent thrombosis occurring within 1 year after stenting, was evaluated. A PATI value <4.8μmol/L was defined as high on-treatment reactivity to ADP. The composite primary endpoint occurred in 55 patients (12.2%) in the 1-year-period after DES implantation, and the prevalence was 19.0% and 5.1% in groups with high and low on-treatment reactivity to ADP, respectively, showing a significantly higher prevalence in the high reactivity group (P<0.001). The main event was TLR (18.1% vs. 5.1%, P<0.001). Conclusions: These data suggested that high on-treatment platelet reactivity to ADP and subsequent occurrence of adverse ischemic events (particularly TLR) were correlated in patients with stable angina who underwent DES implantation. (Circ J 2012; 76: 641-649)

View full abstract

Background: The aim of the present study was to review the clinical profile and outcome of emergency surgery for complicated acute type B aortic dissection. Methods and Results: A total of 34 consecutive patients requiring surgical treatment for complicated acute type B aortic dissection between 2003 and 2010 were examined. The median age was 64.0 years (range, 19-82 years). Indication for emergency surgery was aortic rupture in 11 patients, rapid expansion of the dissecting aorta in 5, dissection involving a non-dissecting aneurysm in 6, and organ malperfusion in 12. All of 3 patients with open aortic rupture died during surgery. Operative mortality was 9.7% (central operation, 14.2%; peripheral operation, 7.1%; thoracic endovascular aneurysm repair, 0%). There were 2 aortic ruptures within 1 week after operation. Two patients suffered from persistent organ malperfusion after emergency surgical relief of ischemia and died. The 1- and 5-year survival rates were 74.1±8.1% and 64.8±11.2%. The actual rate of freedom from aortic events at 1- and 5- years was 83.0±7.0% and 58.7±11.4%. Conclusions: Emergency surgery for complicated acute type B dissection still has a high mortality rate for patients with open rupture and critical visceral ischemia. Medical treatment is best given immediately after admission, and adequate surgical treatment without delay is crucial. (Circ J 2012; 76: 650-654)

View full abstract

Background: Dust storm is a meteorological phenomenon and dust particles have been suspected as harmful to heart and lungs. The aim of this study was to investigate the association between coarse particles and emergency hospital admissions for cardiovascular diseases (CVD) in Hong Kong. Methods and Results: Data on mean daily emergency admissions for CVD to major hospitals in Hong Kong, concentrations of air pollutants and meteorological variables from January 1998 to December 2002 were obtained from several government departments. We identified 5 dust storm days during the study period. Independent t-tests were used to compare the mean daily number of admissions on dust storm and non-dust storm days. Case-crossover analysis, using the Poisson regression, was used to examine the effects of coarse particles' concentration on emergency hospital admissions for CVD. A marginally significant increase in emergency hospital admissions for ischemic heart disease (IHD) was found with RR=1.04 (95% confidence interval: 1.00, 1.08) per 10μg/m³ increase in the concentration of coarse particles. Conclusions: This study demonstrated a marginally significant increase in emergency hospital admissions for IHD on the day of dust storm events in Hong Kong, when the levels of coarse particles were very high. Further studies are required to assess the role of coarse particles on cardiac health. (Circ J 2012; 76: 655-660)

View full abstract

Background: Adaptive servo-ventilation (ASV) has been used as therapy for heart failure (HF). The objective of the present study was to estimate the effect of ASV on 1-year prognosis in HF patients. Methods and Results: After optimizing medical therapy, a 1-year follow-up study was conducted of 85 HF patients (mean age, 72±10 years; 46 men), categorized as New York Heart Association class II-IV. The patients were classified into 2 groups based on adherence to ASV therapy. Use of ASV for ≥4h/night was designated as good adherence, and use of ASV for <4h/night was designated as poor adherence. The incidence of fatal cardiovascular events including death from progression of HF, cardioembolic stroke, and fatal cardiac arrhythmias was tracked. Fifty-seven patients were classified into the good adherence group. After 1-year follow-up, the survival rate calculated using Kaplan-Meier analysis was significantly higher in the good adherence group than in the poor adherence group (P=0.0046, log-rank test). In a Cox proportional hazards model, the odds ratio (95% confidence interval) of fatal cardiovascular events was 0.53 (0.27-0.99) for the good ASV adherence group (P=0.046). Conclusions: ASV prevents fatal cardiovascular events and improves survival in HF patients. (Circ J 2012; 76: 661-667)

View full abstract

Background: The aim of the present study was to assess the safety and tolerability of the controlled-release (CR) formulation of the β-blocker carvedilol in Japanese patients with chronic heart failure (HF). Methods and Results: In this multicenter, randomized, open-label, phase I/II dose-escalation study, 41 patients receiving standard therapy for chronic HF were randomized in a ratio of 1:1 to carvedilol CR or immediate-release (IR) carvedilol. The primary objective was to evaluate the tolerability and safety of escalating doses of carvedilol CR (10-40mg/day), with a reference arm of 5-20mg/day of carvedilol IR. In addition, the tolerability and safety of titration to a carvedilol CR dose up to 80mg/day were examined, as were plasma concentrations of carvedilol and changes in vital signs. The proportions of patients who completed 40-mg/day carvedilol CR and 20-mg/day carvedilol IR were 42% (8/19) and 50% (11/22), respectively. In the CR group, 7/19 (37%) attained a dose of 80mg. During the primary evaluation period, 7/19 (37%) and 4/22 (18%) patients experienced drug-related adverse events in the CR and IR groups, respectively, the characteristics of which were similar between groups. Conclusions: No new safety issues emerged in Japanese chronic HF patients treated with carvedilol CR in contrast to those known in carvedilol IR. (Circ J 2012; 76: 668-674)

View full abstract

Background: The time interval between the onset of early transmitral flow velocity (E) and that of early diastolic mitral annular velocity (e') (T_E-e') is a good predictor of elevated left ventricular (LV) filling pressure in patients with sinus rhythm. Although the evaluation of LV filling pressure using E/e' has been challenging in atrial fibrillation (AF), the usefulness of T_E-e' is unknown. Methods and Results: E and e' were simultaneously recorded using dual Doppler echocardiography in 45 AF patients (30 men; mean age, 69±9 years). E/e' and T_E-e' were calculated and compared with the pulmonary capillary wedge pressure (PCWP), which was measured invasively. E/e' and T_E/e' correlated with PCWP (E/e', r=0.57, P<0.001; T_E-e', r=0.77, P<0.001). Using receiver operating characteristic analysis, the optimal cut-off for T_E-e' was 34ms (sensitivity, 95%; specificity, 88%) and that for E/e' was 14.6 (sensitivity, 50%; specificity, 84%) in order to predict >12-mmHg PCWP. When the combined cut-offs of T_E-e' >34ms and E/e' >14.6 were used, the sensitivity and specificity of predicting elevated PCWP were improved to 100% and 88%, respectively. Conclusions: In AF patients, the simultaneous recording of E and e' using dual Doppler echocardiography and the analysis of T_E-e', in addition to E/e', improved the accuracy of evaluation of LV filling pressure. (Circ J 2012; 76: 675-681)

View full abstract

Background: Left ventricular (LV) mechanical dyssynchrony can lead to impairment of LV function and is associated with adverse clinical outcomes in coronary artery disease (CAD) patients. The impact of LV dyssynchrony on exercise capacity (EC) in patients with CAD was investigated. Methods and Results: An echocardiographic examination with tissue Doppler imaging and exercise treadmill testing in 151 CAD patients with normal LV ejection fraction was performed. LV intra- and inter-ventricular dyssynchrony were defined by the standard deviation of time interval between LV 6 basal segments (Ts-SD), and the time interval from the right ventricular (RV) free wall to LV lateral wall (Ts-RV) respectively, and EC was measured as metabolic equivalents (METs) on the treadmill. Patients with impaired EC (defined by a METs ≤8, which is the mean MET of the study population) were older (71±7 vs. 62±2 years, P<0.01), however, there were no differences in gender and clinical status such as prevalence of prior myocardial infarction (MI), regional wall motion abnormality (RWMA), and coronary revascularization between patients with (n=90) or without (n=61) impaired EC. Univariate analysis showed that age, body mass index, LV systolic and diastolic volume, mitral inflow A velocity, and Ts-SD were all significantly associated with METs (all P<0.05). However, multivariate regression analysis revealed that old age (odd ratio [OR]: 1.136, 95% confidence interval [CI]: 1.080-1.196, P<0.001), and Ts-SD (OR: 1.026, 95%CI: 1.003-1.049, P=0.027) only were independent predictors for impaired EC. Conclusions: In patients with CAD, LV systolic dyssynchrony predicts impaired EC independently of history of previous MI or RWMA. (Circ J 2012; 76: 682-688)

View full abstract

Background: The aim of this study was to propose modified tissue Doppler imaging (TDI) parameters derived from the first active wall motion and to assess them for the better prediction of cardiac resynchronization therapy (CRT) responders in comparison with to original TDI parameters. Methods and Results: In 61 patients with CRT, time from QRS onset to peak velocities by TDI (Ts), which were derived from active wall motion identified by longitudinal strain rate (LSR) value, were assessed. Time from QRS onset to the negative peak of LSR (TLSR) was also assessed. Modified standard deviation of Ts in 12 left ventricular (LV) segments (Ts-SD), that of TLSR (TLSR-SD), differences of Ts between septum and lateral wall (Ts-SL), and that of TLSR (TLSR-SL) were calculated. Original Ts-SD and Ts-SL were calculated by previously described methods. Responders were defined as patients with LV end-systolic volume reduction (>15%) at 6 months after CRT: 35 patients (57%) were identified as CRT responders. Area under the receiver-operating characteristics curve (AUC) of modified Ts-SD (0.87) was significantly higher than that of Ts-SD (0.65), Ts-SL (0.62), and TLSR-SL (0.69). AUC of modified Ts-SL was significantly higher than those of Ts-SD, and Ts-SL. AUC of TLSR-SD (0.82) also was significantly higher than that of Ts-SD. Conclusions: Modified TDI dyssynchrony parameters derived from the first active wall motion improve the ability to predict responders to CRT. (Circ J 2012; 76: 689-697)

View full abstract

Background: The clinical impact of stent edge dissection, tissue protrusion, and incomplete stent apposition (ISA) after stent implantation, detectable only on optical coherence tomography (OCT), is still unknown because the natural course has not been investigated. Methods and Results: All consecutive patients with angina pectoris in whom both intravascular ultrasound (IVUS) and OCT were performed immediately after stenting and at follow-up were included in the present study. The natural history of OCT-detected stent edge dissection, tissue protrusion, and ISA during follow-up was investigated. A total of 36 patients with 39 lesions was analyzed. At baseline, OCT showed 12 stent edge dissections, 25 tissue protrusions, and 8 ISAs, whereas IVUS demonstrated 6 stent edge dissections, 5 tissue protrusions, and 3 ISAs. All IVUS findings were clearly visualized on OCT. The maximum length of dissection flap and depth of ISA visualized on OCT were significantly shorter than those visualized on IVUS. Maximum length of tissue protrusion tended to be smaller on OCT than on IVUS. At follow-up (median 188 days), all findings noted on OCT were healed or resolved without any restenosis or thrombus formation. Conclusions: Acute findings after stenting, such as edge dissection, tissue protrusion, and ISA, detectable only on OCT, tended to be smaller than those seen on both OCT and IVUS. The majority of OCT-detected acute findings resolved completely at follow-up. (Circ J 2012; 76: 698-703)

View full abstract

Background: It is unclear whether platelet count (PLT) is independently associated with clinical outcome in patients with acute coronary syndrome (ACS). Methods and Results: MEDLINE, EMBASE, the Cochrane library clinical trials registry, ISI Science Citation Index, and ISI Web of Knowledge were searched, supplemented by hand-scanning of references of relevant publications and contacting content experts. Eight studies including 39,324 patients were identified that addressed the following issues: major adverse cardiac events (MACE) and mortality were defined as endpoints; the relative risk (RR) or relative odds and their variance with MACE associated with PLT; studies in which only PLT was quantified. Two investigators independently abstracted information on study design, study and participant characteristics, PLT, clinical outcomes, control for potential confounding factors and risk estimates using a standardized protocol. At 1-month follow-up, compared with the bottom PLT group (<150×10⁹/L), the pooled RRs of mortality and MACE were 1.78 (P=0.14) and 1.63 (P<0.001) for the upper PLT (>350×10⁹/L), respectively. At long-term follow-up (≥1 year), the pooled RRs of mortality and MACE were 1.48 (P=0.02) and 1.28 (P=0.02) for the upper PLT, respectively. Moreover, the pooled RR of longitudinal mortality was 1.024 (P=0.03) when PLT was used as a continuous variable. Conclusions: Higher PLT at baseline increases the RR of mortality and MACE in ACS patients. (Circ J 2012; 76: 704-711)

View full abstract

Background: Postprandial hyperglycemia and hyperinsulinemia have been considered as important determinants for the development of atherosclerosis. However, it remains to be elucidated whether correction of the postprandial glycemic status prevents atherosclerotic changes. Methods and Results: The DIANA (DIAbetes and diffuse coronary NArrowing) study is a prospective randomized open-label multicenter trial. The 302 patients with coronary artery disease (CAD), impaired glucose tolerance/diabetes mellitus (DM) pattern according to 75-g oral glucose tolerance test and HbA_1c <6.9% were randomly assigned to life-style intervention (n=101), voglibose (0.9mg/day, n=100) or nateglinide treatment (180mg/day, n=101). We compared 1-year coronary atherosclerotic changes evaluated by quantitative coronary arteriography. Although voglibose significantly increased the number of patients with normal glucose tolerance at 1 year, there were no significant differences in coronary atherosclerotic changes at 1 year. However, overall, less atheroma progression was observed in patients in whom glycemic status was improved at 1 year (%change in total lesion length: 3.5% vs. 26.2%, P<0.01, %change in averaged lesion length: 0.7% vs. 18.6%, P=0.02). Conclusions: Although coronary atherosclerotic changes were similar for voglibose and nateglinide, an improvement in glycemic status at 1 year was associated with less atheroma progression regardless of the treatment. Our findings underscore the management of glycemic abnormality to prevent coronary atherosclerotic changes in Japanese early-stage DM patients with CAD. (Circ J 2012; 76: 712-720)

View full abstract

Background: Coronary artery bypass grafting (CABG) has been the treatment of choice for management of multivessel coronary artery disease, but percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is increasingly being preferred. The aim of the present study was to compare outcomes of PCI with DES implantation (PCI-DES) and CABG for treating multivessel disease in metabolic syndrome patients with acute myocardial infarction (AMI). Methods and Results: A total of 1,839 consecutive metabolic syndrome patients with AMI who underwent PCI-DES (n=1,715) and CABG (n=124) for treatment of multivessel disease were selected from Korea Acute Myocardial Infarction Registry from November 2005 through December 2006. Primary endpoint was 12-month all-cause mortality. The mortality rate at 12 months was significantly lower in the PCI-DES group (4.8% vs. 12.2% in CABG, P=0.014) on univariate analysis. According to a Cox model, 12-month mortality was similar between the 2 groups (P=0.603), which remained the same despite propensity score adjustment (P=0.485). Rate of repeat revascularization was significantly higher in the PCI-DES group compared to the CABG group (P<0.001). At 12 months, major adverse cardiovascular and cerebrovascular event (MACCE)-free survival was higher in ST-elevation MI (STEMI) patients in the CABG group. Conclusions: PCI-DES had an equivalent 12-month mortality risk to CABG for the treatment of multivessel disease in metabolic syndrome patients with AMI. CABG is more favorable for STEMI patients in terms of MACCE. (Circ J 2012; 76: 721-728)

View full abstract

Background: Increased numbers of endothelial (EMP) and platelet (PMP) microparticles have been related to cardiovascular risk factors and coronary artery disease. Little is known about the early effects of statins and clopidogrel on these new biomarkers of vascular homeostasis. The aim of the present study was to evaluate pharmacokinetic interactions between atorvastatin and clopidogrel and their effects, alone or combined, on EMP, PMP, and endothelial progenitor cells (EPC). Methods and Results: A prospective open-label study enrolled subjects with stable coronary disease (n=26). Drugs were given daily for 3 weeks (atorvastatin 80mg, visits 1-3; clopidogrel 75mg, visits 2-4). Counts of EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+), and pharmacokinetic parameters over 24h were assessed at each visit. Atorvastatin plasma concentrations were increased by concomitant therapy with clopidogrel (maximum serum concentration [C_max], P=0.002; area under the clopidogrel or atorvastatin plasma concentration vs. time curve from 0 to the last detectable concentration [AUC_last], P=0.03). After atorvastatin withdrawal there was an increase in clopidogrel plasma concentrations (C_max, P=0.009; AUC_last, P=0.039). PMP were inversely correlated with clopidogrel C_max on visit 3 (rho=-0.57, P=0.006) and on visit 4 (rho=-0.54, P=0.01), and with clopidogrel AUC_last on visit 3 (rho=-0.44, P=0.04), and on visit 4 (rho=-0.57, P=0.005). In addition, clopidogrel C_max was correlated with EPC (CD133+/KDR+) on visit 4 (rho=0.48, P=0.025). No correlations of atorvastatin and MP or EPC were found. Conclusions: The balance between platelet MP release and EPC mobilization seems influenced by clopidogrel plasma levels, suggesting a protective mechanism on coronary artery disease. (Circ J 2012; 76: 729-736)

View full abstract

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disorder mostly caused by desmosome gene mutations. Recent comprehensive desmosome mutation analyses of Caucasian ARVC patients have revealed the presence of not only a single heterozygous mutation, but also compound and digenic heterozygosity. However, the genetic basis of Japanese ARVC remains poorly elucidated. Methods and Results: The subjects were 7 definite and 1 possible ARVC probands (6 males, 16-76 years of age), and their family members. Genetic screening for major ARVC-causing genes (junction plakoglobin, desmoplakin, plakophilin-2 (PKP2), desmoglein-2 (DSG2), and desmocollin-2) was performed. We identified 3 cases of compound heterozygosities (Case 1: DSG2 S194L and DSG2 R292C; Case 2: PKP2 2489+1G>A and PKP2 D812N; Case 3: PKP2 M565R and PKP2 D812N) and 1 of digenic heterozygosity (Case 4: PKP2 1728_1729insGATG and DSG2 R292C) among the definite ARVC patients. All family members we investigated have remained asymptomatic. They carried, if any, only a single variant, indicating that the probands carry in trans compound heterozygosity. These results suggest that each of these variants alone may not be sufficient and second variants may be required to manifest overt ARVC in Japanese patients. Conclusions: Our comprehensive genetic analysis of desmosome genes identified 3 cases of compound heterozygosities in trans and 1 of digenic heterozygosity among 7 definite Japanese ARVC patients, providing novel insights into the genetic basis of Japanese ARVC. (Circ J 2012; 76: 737-743)

View full abstract

Background: The purpose of this study was to investigate whether patients with severe aortic stenosis (AS) and preserved ejection fraction (EF) have dyssynchrony and whether it improves after aortic valve replacement (AVR). Methods and Results: We studied 30 consecutive patients with severe AS and preserved EF undergoing AVR. For baseline comparison, we studied 17 EF-matched patients with mild-to-moderate AS, and 18 EF-matched normal volunteers. Longitudinal dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain in apical 4- and 2-chamber views at the basal- and mid-levels. Radial and circumferential dyssynchrony was determined as the difference for time-to-peak strain between the anteroseptum and posterior wall from the mid-left ventricular (LV) short-axis view. Each of the myocardial functions was also evaluated by averaging each peak systolic strain. Longitudinal dyssynchrony and function in patients with severe AS was significantly worse than in the patients with mild-to-moderate AS and the controls (94±46 vs. 66±18ms* and 52±17ms*, and 12.5±3.7% vs. 16±3.5%* and 18.7±3.7%*, respectively, *P<0.05, vs. severe AS). In contrast, radial and circumferential dyssynchrony were similar for the 3 groups. Importantly, the dyssynchrony of patients with severe AS significantly improved after AVR from 94±46ms to 68±22ms (P<0.005). Conclusions: Significant longitudinal dyssynchrony was present in patients with severe AS and preserved EF, and it improved after AVR. (Circ J 2012; 76: 744-751)

View full abstract

Background: Since the revision of the Japanese Organ Transplantation Act, children younger than 15 years old can donate their organs after brain death. Methods and Results: A teenage boy with endstage restrictive cardiomyopathy underwent the first heart transplantation with a pediatric donor heart in Japan on April 12, 2011. He had a good postoperative clinical course and no histological rejection episodes. His waiting period was relatively short (237 days) compared with adult patients, because of the pediatric patient-first policy for a pediatric donor heart. Conclusions: To increase pediatric heart transplantation in Japan, further enlightenment of the general population about pediatric organ donation is desirable. (Circ J 2012; 76: 752-754)

View full abstract

Background: The distribution of activated partial thromboplastin time (APTT) in nonvalvular atrial fibrillation (NVAF) patients under dabigatran therapy remains to be clarified. Methods and Results: The study population was 196 NVAF patients who were treated with dabigatran in 2011 (126 with 220mg/day). The APTT values showed a wide distribution among the patients, especially in those with a reduced dose, who seemed to show a high value even in patients without contraindications. Conclusions: We found a wide distribution of APTT in NVAF patients under dabigatran treatment. High APTT might help screen for bleeding risks among patients under dabigatran, but requires future investigation. (Circ J 2012; 76: 755-757)

View full abstract

(Circ J 2012; 76: 65-70)

View full abstract