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Journal: Circulation journal : official journal of the Japanese Circulation Society

153

To determine the feasibility of original aortic valve reconstruction (AVRec) for patients with aortic stenosis (AS), 416 consecutive cases were reviewed.Methods and Results:AVRecs for AS were performed for 416 patients from April 2007 through April 2013. All 416 patients were retrospectively reviewed. One hundred and fourteen patients had bicuspid valves and 16 had unicuspid valves. There were 182 men and 234 women. Mean age was 71.2±12.0 years old. On preoperative echocardiography, peak pressure gradient averaged 79.0±33.6 mmHg. Surgical annular diameter was 20.1±2.8 mm. The procedure is based on independent tricuspid replacement by autologous pericardium using original sizing apparatus and template. There was no conversion to prosthetic valve replacement. There were 8 in-hospital mortalities due to non-cardiac cause. On postoperative echocardiography, peak pressure gradient averaged 21.2±10.7 mmHg 1 week after surgery and 14.3±5.0 mmHg 5.5 years after surgery. Four reoperations were done for infective endocarditis. The other 412 patients had less than mild regurgitation. No thrombo-embolic events were recorded. The mean follow-up period was 25.2±17.5 months. Freedom from reoperation was 96.7% with 73-month follow-up.

Concepts: Heart, Surgery, Infective endocarditis, Tricuspid valve, Aortic valve, Valvular heart disease, Valve, Torr

148

The association between serum uric acid (UA) levels and atrial fibrillation (AF) in the general population in Japan is not well known.Methods and Results:In total, 285,882 consecutive subjects (men, 130,897; women, 154,985; age, 58±15 years) not receiving treatment for hyperuricemia who underwent health checkups were enrolled. Subjects were stratified into deciles according to age, body mass index, estimated glomerular filtration rate, systolic blood pressure, and UA level. AF prevalence was calculated for each decile. The odds ratio that defined the decile with the lowest AF prevalence as reference was calculated in each sex. In men, the mean UA was 6.0±1.4 mg/dl; AF prevalence was 1.8% and was lowest in the decile with UA 4.4-4.9 mg/dl. Deciles with both high and low UA (5.4-5.6 mg/dl to >7.8 mg/dl and <4.3 mg/dl) were associated with significantly higher AF prevalence. In women, the mean UA was 4.5±1.1 mg/dl; AF prevalence was 0.7% and was lowest in the decile with UA 3.6-3.8 mg/dl. Deciles with highest UA (5.0-5.2 mg/dl to >5.9 mg/dl) were associated with significantly higher AF prevalence. The analysis adjusted for other clinical covariates demonstrated an independent association between UA and AF in both sexes.

Concepts: Blood, Atherosclerosis, Stroke, Atrial fibrillation, Blood pressure, Body mass index, Urea, Uric acid

147

The edge vascular response (EVR) has been linked to important prognostic implications in patients treated with permanent metallic stents. We aimed to investigate the relationship of EVR with the geometric changes in the everolimus-eluting bioresorbable scaffold using serial optical coherence tomography (OCT) analysis.Methods and Results:In the first-in-man ABSORB trial, 28 patients (29 lesions) underwent serial OCT at 4 different time points (Cohort B1: post-procedure, 6, 24, and 60 months [n=13]; Cohort B2: post-procedure, 12, 36, and 60 months [n=15]) following implantation of the scaffold. In Cohort B1, there was no significant luminal change at the distal or proximal edge segment throughout the entire follow-up. In contrast, there was a significant reduction of the lumen flow area (LFA) of the scaffold between post-procedure and 6 months (-1.03±0.49 mm(2)[P<0.001]), whereas between 6 and 60 months the LFA remained stable (+0.31±1.00 mm(2)[P=0.293]). In Cohort B2, there was a significant luminal reduction of the proximal edge between post-procedure and 12 months (-0.57±0.74 mm(2)[P=0.017]), whereas the lumen area remained stable (-0.26±1.22 mm(2)[P=0.462]) between 12 and 60 months. The scaffold LFA showed a change similar to that observed in Cohort B1.

Concepts: Optics, Medical imaging, Optical coherence tomography, 6

146

A patent foramen ovale (PFO) is common and found in nearly 25% of healthy individuals. The majority of patients with PFO remain asymptomatic and they are not at increased risk for developing a stroke. The presence of PFO, however, has been found to be higher in patients with cryptogenic stroke, suggesting there may be a subset of patients with PFO who are indeed at risk for stroke. Paradoxical embolization of venous thrombi through the PFO, which then enter the arterial circulation, is hypothesized to account for this relationship. Although aerated-saline transesophageal echocardiography is the gold standard for diagnosis, aerated-saline transthoracic echocardiography and transcranial Doppler are often used as the initial diagnostic tests for detecting PFO. Patients with cryptogenic stroke and PFO are generally treated with antiplatelet therapy in the absence of another condition for which anticoagulation is necessary. Based on the findings of 3 large randomized clinical trials, current consensus guidelines do not recommend percutaneous closure, though this is an area of controversy. The following review discusses the relationship of PFO and cryptogenic stroke, focusing on the epidemiology, pathophysiological mechanisms, diagnostic tools, associated clinical/anatomic factors and treatment.

Concepts: Epidemiology, Doppler echocardiography, Echocardiography, Contrast-enhanced ultrasound, Atrial septal defect, Foramen ovale, Ostium primum, Cardiac shunt

146

The aim of this study was to investigate the prognostic impact of acute-phase ventricular tachycardia and fibrillation (VT/VF) on ST-segment elevation myocardial infarction (STEMI) patients in the percutaneous coronary intervention (PCI) era.Methods and Results:Using the database of the Osaka Acute Coronary Insufficiency Study (OACIS), we studied 4,283 consecutive patients with STEMI who were hospitalized within 12 h of STEMI onset and underwent emergency PCI. Acute-phase VT/VF, defined as ≥3 consecutive ventricular premature complexes and/or VF within the 1st week of hospitalization, occurred in 997 (23.3%) patients. In-hospital mortality risk was significantly higher in patients with acute-phase VT/VF than inthose without (14.6% vs. 4.3%, adjusted hazard ratio (HR) 1.83, P=0.0013). Among patients discharged alive, 5-year mortality rates were comparable between patients with and without acute-phase VT/VF. Subgroup analysis showed that acute-phase VT/VF was associated with increased 5-year mortality after discharge in high-risk patients (GRACE Risk Score ≥115; adjusted HR 1.60, P=0.043), but not in intermediate- or low-risk patients.

Concepts: Myocardial infarction, Atherosclerosis, Cardiology, Percutaneous coronary intervention, Ventricular tachycardia, Acute coronary syndrome, Ventricular fibrillation, Premature ventricular contraction

144

Previous research has demonstrated that ClC-3 is responsible for volume-regulated Cl(-)current (ICl.vol) in vascular smooth muscle cells (VSMCs). However, it is still not clear whether and how ClC-3 is transported to cell membranes, resulting in alteration ofICl.vol.Methods and Results:Volume-regulated chloride current (ICl.vol) was recorded by whole-cell patch clamp recording, and Western blotting and co-immunoprecipitation were performed to examine protein expression and protein-protein interaction. Live cell imaging was used to observe ClC-3 transporting. The results showed that an overexpression of endophilin A2 could increaseICl.vol, while endophilin A2 knockdown decreasedICl.vol. In addition, the SH3 domain of endophilin A2 mediated its interaction with ClC-3 and promotes ClC-3 transportation from the cytoplasm to cell membranes. The regulation of ClC-3 channel activity was also verified in basilar arterial smooth muscle cells (BASMCs) isolated from endophilin A2 transgenic mice. Moreover, endophilin A2 increase VSMCs proliferation induced by endothelin-1 or hypo-osmolarity.

Concepts: Protein, Gene expression, Molecular biology, Cell membrane, Cytoplasm, Ion channel, Smooth muscle, Vascular smooth muscle

134

Transplantation of stem/progenitor cells is a promising, emerging treatment for heart failure (HF) in the modern era. Mesenchymal stem/stromal cells (MSCs) are considered as one of the most promising cell sources for this purpose, because of their powerful secretion of reparative factors and immunomodulatory ability. To date, various sources of MSCs have been examined for the treatment of HF in preclinical or clinical studies, including adult tissues (bone marrow and adipose tissue), perinatal tissues (umbilical cord and amnion), and pluripotent stem cells (induced pluripotent stem cells and embryonic stem cells). Adult tissue-derived MSCs have been more extensively examined. Previous clinical trials have suggested the safety and feasibility of these MSCs in HF treatment, but their therapeutic effects remain arguable. Perinatal tissue-derived MSCs have the advantages of removing the necessity of invasiveness biopsy and of mass production. An increasing number of clinical studies (albeit early stage) have been conducted. Pluripotent stem cell-derived MSCs may be another promising source because of their mass-production ability underpinned by their unlimited expansion with consistent quality. However, the risk of tumorigenicity restricts their clinical application. In this review, we summarize the current information available from preclinical and clinical studies, highlighting the advantages and disadvantages of each MSC type. This will provide an insight into consideration of the best MSC source for the treatment of HF.

56

Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain.Methods and Results:In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group.

Concepts: Better, Statistics, Improve, Cardiology, Obesity, Body mass index, Ratio, Brain natriuretic peptide

54

Evidence from prospective cohort studies regarding the relationship between working hours and risk of cardiovascular disease is limited Methods and Results: The Japan Public Health Center-Based Prospective Study Cohort II involved 15,277 men aged 40-59 years at the baseline survey in 1993. Respondents were followed up until 2012. During the median 20 years of follow up (257,229 person-years), we observed 212 cases of acute myocardial infarction and 745 stroke events. Cox proportional hazards models adjusted for sociodemographic factors, cardiovascular risk factors, and occupation showed that multivariable-adjusted hazard ratios (HRs) associated with overtime work of ≥11h/day were: 1.63 (95% confidence interval [CI] 1.01-2.63) for acute myocardial infarction and 0.83 (95% CI 0.60-1.13) for total stroke, as compared with the reference group (working 7 to <9 h/day). In the multivariable model, increased risk of acute myocardial infarction associated with overtime work of ≥11 h/day was more evident among salaried employees (HR 2.11, 95% CI 1.03-4.35) and men aged 50-59 years (HR 2.60, 95% CI 1.42-4.77).

26

Coffee, which contains various bioactive compounds, is one of the most popular beverages. Further accumulation of evidence is needed, however, to confirm whether coffee consumption would be effective in preventing cardiovascular disease in the general Japanese population. Methods and Results: We evaluated the association between coffee consumption frequency (never, sometimes, 1-2 cups/day, 3-4 cups/day and ≥5 cups/day) and mortality from all causes, heart disease, and cerebrovascular disease, in 39,685 men and 43,124 women aged 40-79 years at baseline, in a 3-prefecture cohort study. The coffee consumption frequency was assessed on questionnaire. Cox proportional hazards regression modeling was used to assess the association between coffee consumption frequency and all-cause and cardiovascular disease mortality with adjustment for potential confounders. During 411,341 and 472,433 person-years in men and women, respectively, a total of 7,955 men and 5,725 women died. Coffee consumption frequency was inversely associated with all-cause mortality in both genders (P for trend<0.001). In addition, the risks of mortality from cerebrovascular disease in men (P for trend<0.001), and heart disease in women (P for trend=0.031) were inversely associated with coffee consumption.