Association between induction of the self-management system for preventing readmission and disease severity and length of readmission in patients with heart failure.

OBJECTIVE: We recently developed the self-management system using the HF points and instructions to visit hospitals or clinics when the points exceed the pre-specified levels. We found that the self-management system decreased the hospitalization for HF with an increase in unplanned visits and early intervention in the outpatient department. However, it is unclear whether we managed severe HF outpatients who should have been hospitalized. In this study, we aimed to compare HF severity in rehospitalized patients with regard to self-management system use. RESULTS: We retrospectively enrolled 306 patients (153 patients each in the system user and non-user groups) using propensity scores (PS). We compared HF severity and length of readmission in rehospitalized patients in both groups. During the 1-year follow-up period, 24 system users and 43 non-system users in the PS-matched cohort were hospitalized. There were no significant differences between the groups in terms of brain natriuretic peptide levels at readmission, maximum daily intravenous furosemide dose, percentage of patients requiring intravenous inotropes, duration of hospital stay and in-hospital mortality. These results suggest that the HF severity in rehospitalized patients was not different between the two groups.

Discrepancy between left ventricular hypertrophy by echocardiography and electrocardiographic hypertrophy: clinical characteristics and outcomes.

BACKGROUND: The clinical significance of the discrepancy between left ventricular hypertrophy (LVH) by echocardiography and ECG remains to be elucidated. METHODS: After excluding patients who presented with pacemaker placement, QRS duration ≥120 ms and cardiomyopathy and moderate to severe valvular disease, we retrospectively analysed 3212 patients who had undergone both scheduled transthoracic echocardiography (echo) and ECG in a hospital-based population. Cornell product >2440 mm · ms was defined as ECG-based LVH; left ventricular mass index >115 g/m2 for men and >95 g/m2 for women was defined as echo-based LVH. The study population was categorised into four groups: patients with both ECG-based and echo-based LVH (N=131, 4.1%), those with only echo-based LVH (N=156, 4.9%), those with only ECG-based LVH (N=409, 12.7%) and those with no LVH (N=2516, 78.3%). RESULTS: The cumulative 3-year incidences of a composite of all-cause death and major adverse cardiovascular events were 32.0%, 33.8%, 19.2% and 15.7%, respectively. After adjusting for confounders, the HRs relative to that in no LVH were 1.63 (95% CI 1.16 to 2.28), 1.68 (95% CI 1.23 to 2.30) and 1.09 (95% CI 0.85 to 1.41) in patients with both ECG-based and echo-based LVH, those with only echo-based LVH, and those with only ECG-based LVH, respectively. CONCLUSIONS: Echo-based LVH without ECG-based LVH was associated with a significant risk of adverse clinical events, and the risk was comparable to that in patients with both echo-based and ECG-based LVH.

Clinical impact of left and right axis deviations with narrow QRS complex on 3-year outcomes in a hospital-based population in Japan.

While the prognostic impact of QRS axis deviation has been assessed, it has never been investigated in patients without conduction block. Thus, we evaluated the prognostic impact of QRS-axis deviation in patients without conduction block. We retrospectively analyzed 3353 patients who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in a hospital-based population, after excluding patients with a QRS duration of ≥ 110 ms, pacemaker placement, and an QRS-axis - 90° to - 180° (northwest axis). The study population was categorized into three groups depending on the mean frontal plane QRS axis as follows: patients with left axis deviation (N = 171), those with right axis deviation (N = 94), and those with normal axis (N = 3088). The primary outcome was a composite of all-cause death and major adverse cardiovascular events. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the left axis deviation group (26.4% in the left axis deviation, 22.7% in the right axis deviation, and 18.4% in the normal axis groups, log-rank P = 0.004). After adjusting for confounders, the excess risk of primary outcome measure remained significant in the left axis deviation group (hazard ratio [HR] 1.44; 95% confidence interval [CI] 1.07-1.95; P = 0.02), while the excess risk of primary outcome measure was not significant in the right axis deviation group (HR 1.22; 95% CI 0.76-1.96; P = 0.41). Left axis deviation was associated with a higher risk of a composite of all-cause death and major adverse cardiovascular events in hospital-based patients without conduction block in Japan.

Association of the induction of a self-care management system with 1-year outcomes in patients hospitalized for heart failure.

BACKGROUND: To perform self-care in patients with heart failure (HF), we developed and implemented a new HF point self-care system, which was characterized by 1) the way weight and HF symptoms were scored ("Heart Failure Points") and 2) the timing of consultations defined for both patients and health care providers. We examined the association between the induction of the new system and 1-year outcomes in patients hospitalized for HF. METHODS: We retrospectively enrolled 569 consecutive patients into our study who were admitted for HF treatment at our hospital: 275 patients between November 2011 and October 2013 (before the induction of the self-management system) and 294 patients between November 2015 and October 2017 (after the induction). We sought to compare the clinical outcomes between patients using the self-management system and those not using the system after propensity-score (PS) matching. The primary outcome measure was a composite of all-cause death or HF rehospitalization. RESULTS: The cumulative 1-year incidence of the primary outcome measure in the use group (n = 153) was significantly lower than that in the non-use group (n = 153) (24.5% vs. 34.9%, respectively; p = 0.031; hazard ratio: 0.62; 95% confidence interval: 0.40-0.96), mainly due to a reduction in HF hospitalization. CONCLUSIONS: The induction of the new self-care system was associated with better 1-year outcomes in patients hospitalized for HF. This system may help patients with HF to achieve more efficient self-care.

Temporal trends in prevalence and outcomes of atrial fibrillation in patients undergoing percutaneous coronary intervention.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients undergoing percutaneous coronary intervention (PCI). HYPOTHESIS: Large administrative data may provide further insight into temporal trends in the prevalence and burden of AF in patients who underwent PCI. METHODS: Using the National Inpatient Sample database in the U.S., AF patients ≥18 years who underwent PCI between 2005 and 2014 and were identified by the International Classification of Diseases, ninth revision, Clinical Modification, were examined. In-hospital mortality, morbidity, resource use, and medical costs were evaluated in crude and propensity-matched analyses. RESULTS: Among an estimated 6 272 232 hospitalizations, of patients undergoing PCI, AF prevalence was 9.9% and steadily increased from 8.6% to 12.0% between 2005 and 2014 (P < .001); there was also a greater proportion of comorbidities. There was a marked increase in AF prevalence among those aged ≥65 years and those undergoing elective PCIs. AF was independently associated with higher in-hospital mortality and higher rates of transient ischaemic attack/stroke, bleeding complications, and non-home discharge. Excessive in-hospital mortality, stroke rate, gastrointestinal bleeding, blood transfusion, length of stay, and costs among AF hospitalizations were consistently observed throughout the study period. CONCLUSION: AF becomes more prevalent in patients undergoing PCI, possibly due to a higher comorbidity, particularly in elderly patients with non-acute indications. Less favorable trends in mortality, bleeding, and stroke among AF patients who underwent PCI were consistent over time. Continuous efforts are needed to improve outcomes and manage strategies for AF patients undergoing PCI.

Thirty-Day Readmission After Infective Endocarditis: Analysis From a Nationwide Readmission Database.

Background The contemporary incidence of and reasons for early readmission after infective endocarditis ( IE ) are not well known. Therefore, we analyzed 30-day readmission demographics after IE from the US Nationwide Readmission Database. Methods and Results We examined the 2010 to 2014 Nationwide Readmission Database to identify index admissions for a primary diagnosis of IE with survival at discharge. Incidence, reasons, and independent predictors of 30-day unplanned readmissions were analyzed. In total, 11 217 patients (24.8%) were nonelectively readmitted within 30 days among the 45 214 index admissions discharged after IE . The most common causes of readmission were IE (20.5%), sepsis (8.7%), complications of device/graft (8.1%), and congestive heart failure (7.6%). In-hospital mortality and the valvular surgery rates during the readmissions were 8.1% and 9.1%, respectively. Discharge to home or self-care, undergoing valvular surgery, aged ≥60 years, and having private insurance were independently associated with lower rates of 30-day readmission. Length of stay of ≥10 days, congestive heart failure, diabetes mellitus, renal failure, chronic pulmonary disease, peripheral artery disease, and depression were associated with higher risk. The total hospital costs of readmission were $48.7 million per year (median, $11 267; interquartile range, $6021-$25 073), which accounted for 38.6% of the total episodes of care (index+readmission). Conclusions Almost 1 in 4 patients was readmitted within 30 days of admission for IE . The most common reasons were IE , other infectious causes, and cardiac causes. A multidisciplinary approach to determine the surgical indications and close monitoring are necessary to improve outcomes and reduce complications in in-hospital and postdischarge settings.

Incidence, predictors, causes, and costs of 30-day readmission after in-hospital cardiopulmonary resuscitation in the United States.

BACKGROUND: Readmissions after in-hospital cardiopulmonary resuscitation (ICPR) are common and contribute to increased health care utilization and costs. This study aimed to estimate the burden and patterns of 30-day readmission after ICPR from the US Nationwide Readmission Database (NRD). METHODS: Using International Classification of Diseases-Ninth Revision-Clinical Modification codes, patients who underwent ICPR in the 2014 NRD were included. The incidence, predictors, causes, and costs of 30-day readmission were analyzed with discharge weights to obtain national estimates. RESULTS: Among the 27,278 index admissions that survived to hospital discharge after ICPR, 5439 (20.0%) were readmitted within 30 days. Length of stay (LOS) ≥11 days during index hospitalization, chronic pulmonary disease, congestive heart failure, renal failure, discharge from the teaching metropolitan hospital, Medicare insurance, depression, and diabetes were independent predictors of 30-day readmission. The most common causes of readmission among the 5439 cases were sepsis (13.7%), heart failure (10.9%), and respiratory failure (6.4%). The estimated median costs of readmission were $10,498 (interquartile range, $5797-21,364), which accounted for 25.7% of the total episodes of care (index + readmission). The median LOS of readmission was 5 (3-9) days. CONCLUSIONS: Thirty-day readmissions after ICPR were associated with patient comorbidities and significant cost burden. Recognition of these predictors and individualization of care would allow for the provision of appropriate interventions, and reduce readmissions and healthcare costs.

Sclerosing thymoma-like thymic amyloidoma with nephrotic syndrome: a case report.

BACKGROUND: Primary localized amyloidosis presenting as an isolated mediastinal mass is extremely rare, especially in the thymus. Sclerosing thymoma is also an extremely rare anterior mediastinal tumor, pathologically characterized by extensive sclerotic lesions with hyalinization and calcification. Only 14 cases of sclerosing thymoma and five cases of thymic amyloidosis have been reported to date. CASE PRESENTATION: A 78-year-old Japanese woman was diagnosed as having sclerosing thymoma (Masaoka stage IVa pericardial dissemination)-like thymic amyloidoma. She was diagnosed as having either lung cancer or mediastinal tumor with pericardial dissemination, and received palliative treatment. Three years later, she was readmitted with a complaint of general malaise. Since minimal change nephrotic syndrome was suspected based on the disease onset and selectivity index of urinary protein, steroid pulse therapy was started. Subsequently, because a marked reduction in tumor size was observed during maintenance treatment with prednisolone, a thoracoscopic needle biopsy was performed for a definitive diagnosis. According to the pathological findings and clinical investigations, a final diagnosis of sclerosing thymoma (Masaoka stage IVa pericardial dissemination)-like thymic amyloidoma was made. CONCLUSIONS: This is a case report of sclerosing thymoma-like thymic amyloidoma. Both sclerosing thymoma and thymic amyloidoma are extremely rare diseases: only 14 cases of sclerosing thymoma and five cases of thymic amyloidosis have been reported to date. In either diagnosis, our case is the first case in which marked reduction in tumor size was observed with steroid therapy. All reported cases of sclerosing thymomas underwent surgical resection, but steroid therapy to sclerosing thymoma has not been reported. It is still unknown whether steroid therapy is effective or not. The hyalinized components of sclerosing thymoma possibly contain amyloid deposits. The marked reduction in tumor size with steroid therapy may result in amyloid deposits. The association between sclerosing thymoma and thymic amyloidoma remains uncertain. Sclerosing thymoma should be stained with Congo red.

The ReACT Trial: Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial.

OBJECTIVES: The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily clinical practice in Japan. BACKGROUND: The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately. METHODS: In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group. The primary endpoint was defined as a composite of death, myocardial infarction, stroke, emergency hospitalization for acute coronary syndrome, or hospitalization for heart failure over a minimum of 1.5 years follow-up. RESULTS: Between May 2010 and July 2014, 700 patients were enrolled in the trial among 22 participating centers and were randomly assigned to the AF group (n = 349) or the CF group (n = 351). During a median of 4.6 years of follow-up (interquartile range [IQR]: 3.1 to 5.2 years), the cumulative 5-year incidence of the primary endpoint was 22.4% in the AF group and 24.7% in the CF group (hazard ratio: 0.94; 95% confidence interval: 0.67 to 1.31; p = 0.70). Any coronary revascularization within the first year was more frequently performed in AF group than in CF group (12.8% vs. 3.8%; log-rank p < 0.001), although the difference between the 2 groups attenuated over time with a similar cumulative 5-year incidence (19.6% vs. 18.1%; log-rank p = 0.92). CONCLUSIONS: No clinical benefits were observed for routine FUCAG after PCI and early coronary revascularization rates were increased within routine FUCAG strategy in the current trial. (Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial [ReACT]; NCT01123291).

Clinical Characteristics and Social Frailty of Super-Elderly Patients With Heart Failure　- The Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

BACKGROUND: Social background is important in preventing admission/readmission of heart failure (HF) patients. However, few clinical studies have been conducted to assess the social background of these patients, especially elderly patients.Methods and Results:The Kitakawachi Clinical Background and Outcome of Heart Failure (KICKOFF) Registry is a prospective multicenter community-based cohort of HF patients, established in April 2015. We compared the clinical characteristics and social background of the super-elderly group (≥85 years old) and the non-super-elderly group (<85 years old). This study included 647 patients; 11.8% of the super-elderly patients were living alone, 15.6% were living with only a partner, and of these, only 66.7% had the support of other family members. The super-elderly group had less control over their diet and drug therapies than the non-super-elderly group. Most patients in the super-elderly group were registered for long-term care insurance (77.4%); 73.5% of the super-elderly patients could walk independently before admission, but only 55.5% could walk independently at discharge, whereas 94% of the non-super-elderly patients could walk independently before admission and 89.4% could walk independently at discharge. CONCLUSIONS: The KICKOFF Registry provides unique detailed social background information of Japanese patients with HF. Super-elderly patients are at serious risk of social frailty; they need the support of other people and their ability to perform activities of daily living decline when hospitalized.

Relation of contrast-induced nephropathy to long-term mortality after percutaneous coronary intervention.

There is little information on the effect of contrast-induced nephropathy (CIN) on long-term mortality after percutaneous coronary intervention in patients with or without chronic kidney disease (CKD). Of 4,371 patients who had paired serum creatinine (SCr) measurements before and after percutaneous coronary intervention and were discharged alive in the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry, the incidence of CIN (an increase in SCr of ≥0.5 mg/dl from the baseline) was 5% in our study cohort. The rate of CIN in patients with CKD was 11%, although it was 2% without CKD (p <0.0001). During a median follow-up of 42.3 months after discharge, 374 patients (8.6%) died. After adjustment for prespecified confounders, CIN was significantly correlated with long-term mortality in the entire cohort (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.62 to 2.29, p <0.0001) and in patients with CKD (HR 2.62, 95% CI 1.91 to 3.57, p <0.0001) but not in patients without CKD (HR 1.23, 95% CI 0.47 to 2.62, p = 0.6). Sensitivity analyses confirmed these results using the criteria defined as elevations of the SCr by ≥25% and 0.3 mg/dl from the baseline, respectively. In conclusion, CIN was significantly correlated with long-term mortality in patients with CKD but not in those without CKD.

Prognostic utility of T-wave alternans in a real-world population of patients with left ventricular dysfunction: the PREVENT-SCD study.

BACKGROUND: The predictive value of T-wave alternans (TWA) for lethal ventricular tachyarrhythmia in patients with left ventricular (LV) dysfunction is controversial. Also, long-term arrhythmia risk of patients ineligible for the TWA test is unknown. METHODS: This was a multicenter, prospective observational study of patients with LV ejection fraction ≤40% due to ischemic or non-ischemic cardiomyopathies, designed to evaluate the prognostic value of TWA for lethal ventricular tachyarrhythmia. The primary end point was a composite of sudden cardiac death, sustained rapid ventricular tachycardia (VT) or ventricular fibrillation (VF), and appropriate defibrillator therapy for rapid VT or VF. RESULTS: Among 453 patients enrolled in the study, 280 (62%) were eligible for the TWA test. TWA was negative in 82 patients (29%), who accounted for 18% of the total population. The median of follow-up was 36 months. The 3-year event-free rate for the primary end point was significantly higher in TWA-negative patients (97.0%) than in TWA non-negative patients (89.5%, P = 0.037) and those ineligible for the TWA test (84.4%, P = 0.003). Multivariable analysis identified both non-negative TWA [hazard ratio (HR) 4.43; 95% confidence interval (CI) 1.02-19.2; P = 0.047) and ineligibility for the TWA test (HR 6.89; 95% CI 1.59-29.9; P = 0.010) to be independent predictors of the primary end point. CONCLUSIONS: TWA showed high negative predictive ability for lethal ventricular tachyarrhythmia in patients with LV dysfunction, although the TWA-negative patients accounted for only 18% of the entire population. Those ineligible for the TWA test had the highest risk for lethal ventricular tachyarrhythmia.

A novel KCNJ2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil syndrome.

BACKGROUND: Mutations in KCNJ2, a gene encoding the inward rectifier K(+) channel Kir2.1, are associated with Andersen-Tawil syndrome (ATS), which is characterized by (1) ventricular tachyarrhythmias associated with QT (QU)-interval prolongation, (2) periodic paralysis, and (3) dysmorphic features. METHODS AND RESULTS: We identified a novel KCNJ2 mutation, S369X, in a 13-year-old boy with prominent QU-interval prolongation and mild periodic paralysis. The mutation results in the truncation at the middle of the cytoplasmic C-terminal domain that eliminates the endoplasmic reticulum (ER)-to-Golgi export signal. Current recordings from Chinese hamster ovary cells transfected with KCNJ2-S369X exhibited significantly smaller K(+) currents compared with KCNJ2 wild type (WT) (1 µg each) (-84 ± 14 versus -542 ± 46 picoamperes per picofarad [pA/pF]; -140 mV; P<0.0001). Coexpression of the WT and S369X subunits did not show a dominant-negative suppression effect but yielded larger currents than those of WT+S369X (-724 ± 98 pA/pF>-[84+542] pA/pF; 1 µg each; -140 mV). Confocal microscopy analysis showed that the fluorescent protein-tagged S369X subunits were predominantly retained in the ER when expressed alone; however, the expression of S369X subunits to the plasma membrane was partially restored when coexpressed with WT. Fluorescence resonance energy transfer analysis demonstrated direct protein-protein interactions between WT and S369X subunits in the intracellular compartment. CONCLUSIONS: The S369X mutation causes a loss of the ER export motif. However, the trafficking deficiency can be partially rescued by directly assembling with the WT protein, resulting in a limited restoration of plasma membrane localization and channel function. This alleviation may explain why our patient presented with a relatively mild ATS phenotype.

Effect of baseline glycemic level on long-term cardiovascular outcomes after coronary revascularization therapy in patients with type 2 diabetes mellitus treated with hypoglycemic agents.

The present study evaluated the association between preoperative hemoglobin A1c (HbA1c) levels and cardiovascular outcomes in patients with type 2 diabetes mellitus (DM) treated with hypoglycemic agents and undergoing coronary revascularization. We conducted a multicenter registry of Japanese patients undergoing first elective coronary revascularization. The present study included 3,571 patients whose HbA1c value at the index hospitalization was available. Of the 3,571 patients, 2,067 did not have DM and 1,504 had type 2 DM. Of the patients with type 2 DM, 202 had a HbA1c level of <6% (very low HbA1c group [VLG]), 426 had a HbA1c level of > or =6% but <7% (low HbA1c group), 405 had a HbA1c level of '7% but <8% (intermediate HbA1c group), and 471 had a HbA1c level of > or =8% (high HbA1c group). The patients with type 2 DM treated with diet only were not included in the present study. The VLG had the lowest rate of freedom from major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. On multivariate analyses, the low HbA1c group had the lowest hazard ratio for MACE relative to those without DM (hazard ratio 1.13, 95% confidence interval 0.80 to 1.55). The VLG, intermediate HbA1c group, and high HbA1c group were significantly associated with an increased risk of MACE. On multivariate analyses of patients with DM using the low HbA1c group as a reference, a high HbA1c group level was significantly associated with an increased risk of MACE. The VLG and intermediate HbA1c group tended to be associated with an increased risk of MACE (VLG, hazard ratio 1.54, 95% confidence interval 0.98 to 2.40; intermediate HbA1c group, hazard ratio 1.44, 95% confidence interval 0.98 to 2.13). In conclusion, patients with type 2 DM treated with hypoglycemic agents and undergoing first elective coronary revascularization had significantly worse cardiovascular outcomes than patients without DM, except for patients with DM and a HbA1c of 6% to 7%. In the patients with DM, those with a HbA1c of 6% to 7% tended to have the lowest risk of MACE.

Chronic obstructive pulmonary disease--an independent risk factor for long-term cardiac and cardiovascular mortality in patients with ischemic heart disease.

BACKGROUND: Limited data are available on long-term mortality and morbidity of patients with chronic obstructive pulmonary disease (COPD) and ischemic heart disease. We examined how COPD affects long-term mortality and morbidity after undergoing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). METHODS: We analyzed 9877 consecutive patients who underwent their first elective PCI (n=6878) and CABG (n=2999) in 2000-2002 at 30 institutions listed in the CREDO-Kyoto registry. RESULTS: COPD was diagnosed in 240 patients (2.4%). In-hospital mortality (1.3% vs. 1.2%, p=0.972) did not differ between patients with and without COPD. During long-term follow-up (42. 8 month s), 906 patients (9.4%) died, 517 (5.3%) of whom died of cardiovascular death and 376 (3.9%), of cardiac death. At 3 years, the unadjusted survival rate and the rates of freedom from cardiovascular death and cardiac death were 92.1%, 95.3%, and 96.5% in the total population and 82.8%, 91.7%, and 92.1% in patients with COPD respectively. Log-rank test indicated that COPD was associated with higher incidence of all-cause mortality (p<0.0001), cardiovascular death (p=0.0002), and cardiac death (p<0.0001). Multivariate analyses indicated that COPD was an independent predictor of all-cause mortality (hazard ratio 1.36, p=0.0003), cardiovascular death (hazard ratio 1.28, p=0.0407), and cardiac death (hazard ratio 1.48, p=0.003). CONCLUSIONS: COPD is an independent risk factor for long-term cardiac and cardiovascular mortality in patients with ischemic heart disease.

Coronary risk factor profile and prognostic factors for young Japanese patients undergoing coronary revascularization.

BACKGROUND: The prevalence of coronary artery disease (CAD) is increasing in young adults. Risk factor profiling will help to prevent heart attacks in young patients. This study aimed to analyze the risk factor profile and predictors of major cardiovascular events (MACE) in young CAD patients. METHODS AND RESULTS: From the Coronary REvascularization Demonstrating Outcome study in the Kyoto (CREDO-Kyoto) registry of Japanese patients undergoing their first coronary revascularization, 6,320 patients with complete data for all variables for statistical analyses were divided into younger (< or =55 years; n=898; 14.3%) and older (>55 years; n=5,422; 85.7%) patients. The risk factors that were more prevalent in the younger patients than in the older patients included: male sex, body mass index of >25 kg/m(2), current smoker, family history of CAD, dyslipidemia and metabolic syndrome-like risk factor accumulation. Multivariate analyses revealed that chronic kidney disease (CKD) was the only significant predictor of MACE, the composite of cardiovascular death, myocardial infarction and cerebrovascular accident, in the younger patients. Importance of CKD as a prognostic factor was consistently shown by a multivariate analysis in the older patients. CONCLUSIONS: Accumulation of multiple risk factors is prevalent and CKD is associated with MACE in young Japanese CAD patients.

Long-term outcomes of coronary-artery bypass graft surgery versus percutaneous coronary intervention for multivessel coronary artery disease in the bare-metal stent era.

BACKGROUND: Observational registries comparing coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) have reported long-term survival results that are discordant with those of randomized trials. METHODS AND RESULTS: We conducted a multicenter study in Japan enrolling consecutive patients undergoing first CABG or PCI between January 2000 and December 2002. Among 9877 patients enrolled, 5420 (PCI: 3712, CABG: 1708) had multivessel disease without left main involvement. Because age is an important determinant when choosing revascularization strategies, survival analysis was stratified by either age >/=75 or <75 years. Analyses were also performed in other relevant subgroups. Median follow-up interval was 1284 days with 95% follow-up rate at 2 years. At 3 years, unadjusted survival rates were 91.7% and 89.6% in the CABG and PCI groups, respectively (log rank P=0.26). After adjustment for baseline characteristics, survival outcome tended to be better after CABG (hazard ratio for death after PCI versus CABG [HR], 95% confidence interval [CI]: 1.23 [0.99-1.53], P=0.06). Adjusted survival outcomes also tended to be better for CABG among elderly patients (HR [95%CI]: 1.37 [0.98-1.92] P=0.07), but not among nonelderly patients (HR [95% CI]: 1.09 [0.82-1.46], P=0.55). Unadjusted and adjusted survival outcome for CABG and PCI were not significantly different in any subgroups when elderly patients were excluded from analysis. CONCLUSIONS: In the CREDO-Kyoto registry, survival outcomes among patients <75 years of age were similar after PCI and CABG, a result that is consistent with those of randomized trials.

Better survival with statin administration after revascularization therapy in Japanese patients with coronary artery disease: perspectives from the CREDO-Kyoto registry.

BACKGROUND: The importance of statins in cardiovascular prevention has been demonstrated in various patient subsets. This study aimed to evaluate the effects of statins on long-term outcomes of Japanese patients undergoing their first coronary revascularization. METHODS AND RESULTS: A total of 9,225 patients undergoing their first coronary revascularizations during 2000--2002 were divided into 2 groups according to the use of statins at discharge; patients with acute myocardial infarction were not included. Statins was administered to only 28.5% (n=2,630) of the patients. The median follow-up period was 3.5 years. Patients on statin therapy showed lower all-cause (5.2% vs 10.0%; p<0.0001) and cardiovascular (3.2% vs 6.2%; p<0.0001) mortality than those without statins (n=6,595) by Kaplan-Meier analysis and log-rank test. After adjustment by multivariate analysis according to 29 variables, statin therapy remained as an independent predictor of reduced all-cause (relative risk ratio (RR) 0.71, 95% confidence interval (CI) 0.59-0.86, p=0.0005) and cardiovascular (RR 0.72, 95% CI 0.56-0.91, p=0.0067) mortality. The validity of RR of statin therapy in multivariate analysis was further confirmed by risk adjustment using propensity scores (all-cause mortality: propensity-adjusted RR 0.70, 95% CI 0.58-0.85, p=0.0003; cardiovascular mortality: propensity-adjusted RR 0.70, 95% CI 0.54-0.89, p=0.0038). CONCLUSIONS: Statin therapy started at hospital discharge was associated with increased chance of survival in Japanese patients undergoing their first coronary revascularization.

Mutation analysis of the glycerol-3 phosphate dehydrogenase-1 like (GPD1L) gene in Japanese patients with Brugada syndrome.

Brugada syndrome is an inherited arrhythmic disorder, and mutations in the SCN5A gene, encoding cardiac sodium channels, are identified in approximately 15% of cases. A novel causative gene (glycerol-3 phosphate dehydrogenase-1 like; GPD1L) has been reported, and in the present study, 80 unrelated Japanese patients were screened for GPD1L mutations: 1 synonymous mutation was identified, as well as 1 intronic variant, both of which were absent in 220 control alleles. Additionally, a single-nucleotide polymorphism was detected in 4 patients. No non-synonymous mutations were found. GPD1L does not appear to be a major cause of Brugada syndrome in the Japanese population.

Mechanistic basis for the pathogenesis of long QT syndrome associated with a common splicing mutation in KCNQ1 gene.

Mutations in KCNQ1, the gene encoding the delayed rectifier K(+) channel in cardiac muscle, cause long QT syndrome (LQTS). We studied 3 families with LQTS, in whom a guanine to adenine change in the last base of exon 7 (c.1032G>A), previously reported as a common splice-site mutation, was identified. We performed quantitative measurements of exon-skipping KCNQ1 mRNAs caused by this mutation using real-time reverse transcription polymerase chain reaction. Compared with normal individuals who have minor fractions of splicing variants (Delta7-8: 0.1%, Delta8: 6.9%, of total KCNQ1 transcripts), the affected individuals showed remarkable increases of exon-skipping mRNAs (Delta7: 23.5%, Delta7-8: 16.8%, Delta8: 4.5%). Current recordings from Xenopus laevis oocytes heterologously expressing channels of wild-type (WT) or exon-skipping KCNQ1 (Delta7, Delta7-8, or Delta8) revealed that none of the mutants produced any measurable currents, and moreover they displayed mutant-specific degree of dominant-negative effects on WT currents, when co-expressed with WT. Confocal microscopy analysis showed that fluorescent protein-tagged WT was predominantly expressed on the plasma membrane, whereas the mutants showed intracellular distribution. When WT was co-expressed with mutants, the majority of WT co-localized with the mutants in the intracellular space. Finally, we provide evidence showing direct protein-protein interactions between WT and the mutants, by using fluorescence resonance energy transfer. Thus, the mutants may exert their dominant-negative effects by trapping WT intracellularly and thereby interfering its translocation to the plasma membrane. In conclusion, our data provide a mechanistic basis for the pathogenesis of LQTS caused by a splicing mutation in KCNQ1.