Junji Yajima

A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan

AIMS Theoretically, bioresorbable vascular scaffolds (BVSs) may provide superior long-term results compared with permanent metallic drug-eluting stents (DESs). However, whether BVSs are as safe and effective as metallic DESs prior to complete bioresorption is unknown. METHODS AND RESULTS ABSORB Japan was a single-blind, multicentre, active-controlled, randomized trial designed to support regulatory approval of the Absorb BVS in Japan. Eligible patients with one or two de novo lesions in different epicardial vessels were randomized at 38 Japanese sites in a 2:1 ratio to Absorb BVS vs. cobalt-chromium everolimus-eluting stents (CoCr-EESs). The primary endpoint was target lesion failure [TLF: a composite of cardiac death, myocardial infarction attributable to target vessel, or ischaemia-driven target lesion revascularization (ID-TLR)] at 12 months, powered for non-inferiority. The major secondary endpoint was angiographic in-segment late lumen loss (LLL) at 13 months. A total of 400 patients were randomized to BVSs (266 patients and 275 lesions) or CoCr-EESs (134 patients and 137 lesions). TLF through 12 months was 4.2% with BVSs and 3.8% with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.39% (3.95%); Pnon-inferiority < 0.0001]. Definite/probable stent/scaffold thrombosis at 12 months occurred in 1.5% of the patients with both devices (P = 1.0), and ID-TLR for restenosis was infrequent (1.1% with BVSs and 1.5% with CoCr-EESs, P = 1.0). With 96.0% angiographic follow-up, in-segment LLL at 13 months was 0.13 ± 0.30 mm with BVSs and 0.12 ± 0.32 mm with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.01 (0.07); Pnon-inferiority < 0.0001). CONCLUSION In the ABSORB Japan randomized trial, 12-month clinical and 13-month angiographic outcomes of BVSs were comparable to CoCr-EESs. CLINICAL REGISTRATION ClinicalTrials.gov, number NCT01844284.

Brachial-ankle pulse wave velocity as a risk stratification index for the short-term prognosis of type 2 diabetic patients with coronary artery disease

The incidence of diabetes is increasing, and the disease has become an important predictor of prognosis in patients with coronary artery disease (CAD), although adverse events often occur without warning. Thus, risk stratification of diabetic CAD patients is important for secondary prevention. This study tests the hypothesis that brachial-ankle pulse wave velocity (baPWV), a marker for arterial stiffness obtained by simple and noninvasive automated devices, can be a risk stratification index to predict prognosis in diabetic patients with CAD. The prognosis of CAD patients with diabetes in the Shinken Database cohort study was investigated by dividing patients into two groups based on baPWV measurements. The composite endpoint was death, nonfatal myocardial infarction, repeat revascularization or readmission for heart failure. Data were available on 564 CAD patients, with a median follow-up of 25.4 months. Of these patients, 191 had type 2 diabetes. The higher baPWV among diabetic patients was defined as a median baPWV of 1730 cm s–1 or more. The 3-year Kaplan–Meier estimates of event-free survival were 72.8% in diabetic patients with lower baPWV and 51.3% in those with higher baPWV, respectively (P=0.031). Multivariate analysis revealed that a higher baPWV was independently associated with poorer short-term prognosis (hazard ratio, 1.97; 95% confidence interval, 1.01–3.84) in diabetic CAD patients. In conclusion, baPWV, a marker for arterial stiffness, can be a risk stratification index for short-term prognosis in clinical practice, suggesting the need for further aggressive treatment and strict follow-up in CAD patients with diabetes and higher baPWV.

Usefulness of Frequent Supraventricular Extrasystoles and a High CHADS2 Score to Predict First-Time Appearance of Atrial Fibrillation

Frequent supraventricular extrasystoles (SVEs) are associated with the subsequent first-time appearance of atrial fibrillation (AF) and ischemic stroke. The aim of this study was to investigate the combined role of SVEs and an AF-related risk score for ischemic stroke, the CHADS2 score, on the occurrence of new AF in patients in sinus rhythm. The Shinken Database 2004-2010 lists 3,263 patients who underwent 24-hour Holter monitoring. A total of 2,589 patients were analyzed, after excluding 674 patients previously diagnosed with AF. Frequent SVEs were defined as ≥102 beats/day (the top quartile) and the presence of a clinical background for a CHADS2 score ≥2 points as a high CHADS2 score. During the mean follow-up period of 571.4 ± 606.4 days, new AF occurred in 38 patients (9.4 per 1,000 patient-years). The incidence of new AF was 2.7 and 37.7 per 1,000 patient-years for patients with nonfrequent SVEs (<102 beats/day) and low CHADS2 scores and those with frequent SVEs and high CHADS2 scores, respectively. Multivariate Cox regression analysis showed that the hazard ratio for frequent SVEs and a high CHADS2 score compared with nonfrequent SVEs and a low CHADS2 score was 9.49 (95% confidence interval 3.20 to 28.15, p <0.001), even after adjustment for gender, age, medications, and echocardiographic parameters. In conclusion, frequent SVEs and a high CHADS2 score independently and synergistically predict the first-time appearance of AF in patients in sinus rhythm, indicating an approximately 10-fold higher risk. Patients meeting these criteria should have more aggressive early intervention for preventing AF.

Mechanisms of acute gain and late lumen loss after atherectomy in different preintervention arterial remodeling patterns.

The main mechanism of restenosis after directional coronary atherectomy (DCA) remains obscure. We investigated mechanisms of restenosis after DCA in different coronary artery remodeling patterns. DCA was performed in 51 de novo lesions. The lesions were evaluated by intravascular ultrasound (IVUS) before, immediately after, and 6 months after the procedure. According to the IVUS findings before DCA, we classified the lesions into the following 3 groups: (1) positive (n = 10), (2) intermediate (n = 25), and (3) negative (n = 16) remodeling. We measured lumen area, vessel area, and plaque area using IVUS before DCA, immediately after DCA, and at follow-up. Lumen area increase after DCA was mainly due to plaque area reduction in the positive and intermediate remodeling groups (90 plus minus 15% and 80 plus minus 25% increase in lumen area, respectively), whereas that in the negative remodeling group was due to both plaque area reduction (57 plus minus 22% increase in lumen area) and vessel area enlargement (43 plus minus 33% increase in lumen area). The plaque area increase correlated strongly with late lumen area loss in the positive and intermediate remodeling groups (r = 0.884, p <0.001; r = 0.626, p <0.001, respectively), but the decrease in vessel area was not correlated with lumen area loss. In contrast, both an increase in plaque area and a decrease in vessel area were correlated with late lumen area loss (r = 0.632, p = 0.009; r = 0.515, p = 0.041) in the negative remodeling group. Coronary artery restenosis after atherectomy was primarily due to an increase in plaque in the positive and/or intermediate remodeling groups. However, in the negative remodeling group, late lumen loss might have been caused by both an increase in plaque and vessel shrinkage.

Obesity paradox in Japanese patients after percutaneous coronary intervention: An observation cohort study

BACKGROUND The impact of obesity on Japanese patients who undergo primary percutaneous coronary intervention (PCI) remains unclear. METHODS AND RESULTS Within a single hospital-based cohort in the Shinken Database 2004-2010, which comprised all new patients (n=15227) who visited the Cardiovascular Institute, we followed patients who underwent PCI. Major adverse cardiac events (MACE)-death, myocardial infarction, or target lesion revascularization (TLR)-were defined as the composite endpoint. A total of 1205 patients were included in this study (median follow-up of 1037±703 days): 92 lean [body-mass-index (BMI)<20]; 640 normal-weight (BMI=20-24.9); 417 overweight (BMI=25-29.9); and 56 obese (BMI≥30). Mean age decreased and male gender increased with increasing BMI. Classic coronary risk factors were more common in overweight and obese patients than in normal-weight and lean patients. Chronic kidney disease (CKD) was more common in lean patients than in overweight and obese patients. Patients taking dual antiplatelet therapy, statins, beta-blockers, and renin-angiotensin-system inhibitors increased in a BMI-dependent manner. Obese patients had a significantly lower frequency of MACE, all-cause death, cardiac death, and hospital admission for heart failure than lean patients. Multivariate analysis showed that BMI category was independently associated with all-cause death after PCI. CONCLUSION Over-weight and obese patients were independently associated with favorable long-term clinical outcomes after PCI, suggesting that obesity paradox was applicable to Japanese patients after PCI in real-world clinical setting.

Recent mortality of Japanese patients with atrial fibrillation in an urban city of Tokyo.

BACKGROUND In Japan, the recent status of the mortality of atrial fibrillation (AF) patients is still unclear. METHODS AND RESULTS We used a single-hospital based cohort database in an urban city (Tokyo) in Japan, including all the new visitors from 2004 to 2009 (n=13,228). The non-adjusted death rates of AF patients for all-cause, stroke, and cardiovascular death were 1091, 97, and 727 per 100,000 patient-years, and the age-adjusted ones were 317 (95% CI, 316-318), 16 (95% CI, 16-16), and 238 (95% CI, 237-239), respectively. The age-adjusted relative risk of AF on all-cause mortality was 1.7 in the particular population. CONCLUSIONS The present study provides the most recent data about the characteristics and the mortality of AF patients in Tokyo, thus serving as the basic information for finding problems to solve regarding Japanese AF patients.

Clinical characteristics and long-term clinical outcomes of Japanese heart failure patients with preserved versus reduced left ventricular ejection fraction: A prospective cohort of Shinken Database 2004–2011

BACKGROUND Clinical data on the mortality and morbidity of unselected Japanese patients with heart failure (HF) are limited. In this study, we aimed to determine the clinical characteristics, long-term outcomes, and prognostic factors of Japanese HF patients with preserved or reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS We used a single hospital-based cohort from the Shinken Database 2004-2011 that comprised all new patients (n=17,517) visiting the Cardiovascular Institute Hospital. A total of 1,525 patients diagnosed with symptomatic HF at the initial visit were included in the analysis. Of these, 1121 patients (74%) exhibited a preserved LVEF (>50%) and 404 patients (26%) had a reduced LVEF (≤ 50%). HF patients with preserved LVEF (HFpEF) were older and more often female than patients with reduced LVEF (HFrEF). Kaplan-Meier curves and log-rank test results showed that HFpEF patients had a better prognosis than HFrEF patients. However, there were no significant differences in clinical outcomes between HFpEF and HFrEF patients when the analysis was limited to inpatients. Cox regression analysis showed that HFpEF patients had a significantly lower risk of all-cause death (p=0.027; hazard ratio, 0.547, 95% confidence interval, 0.321-0.933). Multivariate analyses performed separately showed that the independent predictors of all-cause death in HFrEF were advanced age, lower body mass index, diabetes mellitus, and the absence of statin treatment, whereas those for HFpEF were advanced age, absence of dyslipidemia, anemia, and left ventricular hypertrophy. CONCLUSIONS This prospective cohort study identified the clinical characteristics, long-term outcomes, and prognostic factors of Japanese HF patients with reduced and preserved ejection fractions in a real-world clinical setting.

Vascular Ehlers-Danlos syndrome: —All three coronary artery spontaneous dissections

Vascular Ehlers-Danlos syndrome is an inherited connective-tissue disorder causing arterial and gastrointestinal fragility and spontaneous rupture of the large arteries, uterus, or bowel. Among arterial dissections and ruptures, spontaneous coronary artery dissection is extremely rare in this disorder. The specific therapeutic strategy for this disorder and its complications has not yet been established. In this report, we describe a 33-year-old woman with all three coronary artery spontaneous dissections, resulting in cardiogenic shock and therapy-resistant ventricular fibrillation. We could successfully complete revascularization of all three coronary arteries and terminate the life-threatening arrhythmia. Biochemical findings finally revealed a point mutation in the COL3A1 gene, consistent with a diagnosis of vascular Ehlers-Danlos syndrome. To the best of our knowledge, this is the first case of vascular Ehlers-Danlos syndrome causing all three coronary artery spontaneous dissections. Our case also suggests that, from vascular fragility even if it is spontaneous coronary dissection, physicians always consider connective-tissue disorders as a differential diagnosis at an early stage even though that would be a first complication, and percutaneous coronary intervention with stenting using intravascular ultrasound could be a strategic option for even repeated and fatal spontaneous coronary artery dissections in vascular Ehlers-Danlos syndrome.

Effects of statin treatment in patients with coronary artery disease and chronic kidney disease.

Statins reduce cardiovascular morbidity and mortality from coronary artery disease (CAD). However, the effects of statin therapy in patients with CAD and chronic kidney disease (CKD) remain unclear. Within a single hospital-based cohort in the Shinken Database 2004–2010 comprising all patients (n = 15,227) who visited the Cardiovascular Institute, we followed patients with CKD and CAD after percutaneous coronary intervention (PCI). A major adverse cardiovascular and cerebrovascular event (MACCE) was defined by composite end points, including death, myocardial infarction, cerebral infarction, cerebral hemorrhage, and target lesion revascularization. A total of 391 patients were included in this study (median follow-up time 905 ± 679 days). Of these, 209 patients used statins. Patients with statin therapy were younger than those without. Obesity and dyslipidemia were more common, and the glomerular filtration rate (GFR) was significantly higher, in patients undergoing statin treatment. MACCE and cardiac death tended to be less common, and all-cause death was significantly less common, in patients taking statins. Multivariate analysis showed that low estimated GFR, poor left ventricular ejection fraction, and the absence of statin therapy were independent predictors for all-cause death of CKD patients after PCI. Statin therapy was associated with reduced all-cause mortality in patients with CKD and CAD after PCI.

Impact of aging on the clinical outcomes of Japanese patients with coronary artery disease after percutaneous coronary intervention

Japan has become an aging society, resulting in an increased prevalence of coronary artery disease. However, clinical outcomes of elderly Japanese patients after percutaneous coronary intervention (PCI) remain unclear. Of the 15,227 patients in the Shinken Database, a single-hospital-based cohort of new patients, 1,214 patients who underwent PCI, was evaluated to determine the differences in clinical outcomes between the elderly (≥75 years) (n = 260) and the non-elderly (<75 years) (n = 954) patients. A major adverse cardiac event (MACE) was defined as a composite end point, including all-cause death, myocardial infarction (MI), and target lesion revascularization. Male gender and obesity were less common, and the estimated glomerular filtration rate (eGFR) was significantly lower in the elderly than in the non-elderly. Left ventricular ejection fraction (LVEF) was comparable between these groups. Left main trunk disease and multivessel disease were more common in the elderly than in the non-elderly group. Occurrence of MACE was frequent, and the incidences of all-cause death, cardiac death, and the admission rate for heart failure were significantly higher in the elderly patients. Multivariate analysis showed that prior MI, low eGFR, and poor LVEF were independent predictors for all-cause death in the elderly patients. Elderly patients had worse clinical outcomes than the non-elderly patients. Low eGFR and LVEF were independent predictors of all-cause death after PCI, suggesting that left ventricular dysfunction and renal dysfunction might synergistically contribute to the adverse clinical outcomes of the elderly patients undergoing PCI.