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Sarcoidosis is a multisystem granulomatous disease of unknown cause. With cardiac sarcoidosis (CS), patients represent a wide range of cardiac manifestations from subtle to overt morphological and functional abnormalities. The advent of ultrasound technologies has enabled to identify not only typical findings to CS such as basal thinning of the ventricular septum, but also subclinical myocardial alterations. Based on our recent experiences, we currently introduce a variety of myocardial manifestations evaluated by echocardiography on seven CS patients being selected. Most of the patients exhibited typical cardiac involvement and the remaining fairly unusual.

Elevated liver fibrosis markers are associated with worse prognosis in acute heart failure (AHF). The aspartate aminotransferase to alanine aminotransferase ratio (AAR) is one such fibrosis marker, and low ALT is a surrogate marker of malnutrition. Here, we evaluated the association between AAR and nutritional status and prognosis in patients with AHF. Consecutive 774 patients who were admitted due to AHF were divided into 3 groups according to AAR at discharge: first tertile, AAR1.16 (n = 262); second tertile, 1.16≤AAR1.70 (n = 257); and third tertile, AAR≥1.70 (n = 255). Nutritional indices and a composite of all-cause death or HF rehospitalization were compared in the 3 tertiles. Patients in the third AAR tertile were older and had lower body mass index than patients in other AAR tertiles. A higher AAR was associated with worse nutritional indices (i.e., controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index). Clinical outcome rates significantly increased along AAR tertiles (first tertile, 28%; second tertile, 43%; third tertile, 58%, p0.001). Cox proportional hazards models including potential prognostic factors revealed high AAR was an independent prognostic factor of AHF. In conclusion, AAR at discharge may be associated with nutritional status and worse clinical outcomes in patients with AHF.

Background Tissue Doppler imaging (TDI)-derived atrial electromechanical delay (AEMD) has been reported to be useful for detecting paroxysmal atrial fibrillation (PAF). However, its usefulness remains unknown when analyzed along with patients seemingly at high-risk for AF as controls. From this standpoint, we investigated whether AEMD would be of use for identifying patients with PAF. Methods We retrospectively analyzed TDI recordings to obtain AEMD in 63 PAF patients. Thirty-three patients with multiple cardiovascular risk factors (MRFs) but without history of AF and 50 healthy individuals served as disease and healthy controls, respectively. AEMD was defined as the time-interval between the electrocardiogram P-wave and the beginning of the spectral TDI-derived A’ for the septal (septal EMD) and lateral (lateral EMD) sides of the mitral annulus. Results There was no significant difference in the left atrial volume index between PAF patients and disease controls (28 ± 9 mL/m2 vs. 27 ± 5 mL/m2). PAF patients had longer AEMD, particularly for the lateral EMD (75 ± 23 ms), compared with disease (62 ± 22 ms, P = 0.009) and healthy (54 ± 24 ms, P P = 0.023), along with the left atrial volume index (OR 2.25, 95%CI 1.44–3.51, P Conclusions This cross-sectional study indicates that even analyzed together with MRFs patients, AEMD remains useful for identifying patients at risk for AF. Our results need to be confirmed by a large-scale prospective study.

Malnutrition and systemic inflammation are associated with poor outcomes in patients with heart failure. Recent studies have reported that the advanced lung cancer inflammation index (ALI), derived from the body mass index (BMI), serum albumin level, and neutrophil-to-lymphocyte ratio (NLR), is associated with poor prognosis in several types of cancers. Each marker is also known to prognostic factor of heart failure. Therefore, we hypothesized that ALI may be useful for determining the prognosis of patients with acute decompensated heart failure (ADHF). We reviewed survival in 381 consecutive patients (age, 73.1 ± 11.4 years, 59% men) who were hospitalized for ADHF and discharged. ALI at discharge, calculated as BMI × albumin level/NLR, was used to divide the patients into tertiles (ALI

Background A lack of adherence and inadequate self-care behaviours are common reasons for recurrent hospitalizations among patients with heart failure (HF). Although patients recognize the importance of HF self-care, it is sometimes difficult to correct their behavioural patterns. Motivational interviewing is a communication technique to resolve ambivalence towards changing behaviour, and it has been widely used to promote behavioural changes and improve outcomes in various chronic diseases. We described a case of advanced HF with reduced ejection fraction in which motivational interviewing lead to stabilize the patient’s condition. Case summary A 33-year-old man was diagnosed with dilated cardiomyopathy who experienced repeated episodes of HF requiring hospitalization despite optimal guideline-based HF treatment. Transthoracic echocardiography disclosed a severely reduced left ventricular (LV) contraction (LV ejection fraction 18%) and cardiopulmonary exercise testing disclosed markedly reduced functional capacity and increased ventilatory response (peak VO2 of 10.7 mL/min/kg, predicted peak VO2 of 34.7% and VE/VCO2 slope of 35.2). In this case, poor adherence to self-care such as excessive fluid intake and excessive daily activities after hospital discharge was the main cause of recurrent hospitalization for HF. Despite repeated patient education to correct his diet and lifestyle, he could not change his lifestyle behaviour. However, motivational interviewing dramatically helped stabilize the patient’s condition and prevent HF re-hospitalization. Discussion In general, patients with advanced HF and reduced ejection fraction despite optimal medical therapy should be evaluated to assess their eligibility of cardiac transplantation or palliative care. Motivational interviewing might represent a new therapeutic approach for stabilizing and preventing HF through self-care behavioural changes, even in patients with advanced HF and severely reduced ejection fraction.

Cardiac sarcoidosis (CS) causes lethal arrhythmia and heart failure and has a poor prognosis; therefore, early detection and early stage treatment are important. However, diagnosis of isolated CS may be difficult in some cases owing to the low sensitivity of myocardial biopsy. Herein, we describe the case of a patient with isolated CS, showing change from negative to positive fluorine‐18 fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET) uptake results within 9 months. The patient showed rapid reduction in left ventricular systolic function with sustained ventricular tachycardia. The diagnosis of isolated CS is often under‐recognized in clinical practice because it commonly requires the diagnosis of extracardiac disease in the absence of a positive endomyocardial biopsy. The Japanese Circulation Society recently published guidelines for CS diagnosis stating that isolated CS can be clinically diagnosed with positive 18F‐FDG PET or 67Gallium result. In this case, serial follow‐up 18F‐FDG PET was useful for diagnosing isolated CS.

Severe ventricular arrhythmias such as high-grade atrioventricular block and ventricular tachycardia may cause lethal conditions or sudden death in patients with cardiac sarcoidosis (CS). Physicians should examine patients carefully for these conditions and treat them appropriately. As arrhythmias are being better diagnosed and treated, physicians are increasingly aware of atrial arrhythmias, which have not been focused upon as CS-related conditions, in patients with CS. This article reports a case of atrial flutter in sarcoidosis, and discusses literature findings on atrial arrhythmias and atrial involvement of CS. It is highly likely that atrial arrhythmia and supraventricular conduction disorder associated with or caused by CS are more common than previously thought. Physicians should pay careful attention for these conditions in the diagnosis and treatment of CS.

Clinical trials with autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHDs) are ongoing. However, little is known about combinational therapeutic effect of AdSCs and statin poly(lactic-co-glycolic) acid (PLGA) nanoparticles on the ischemic myocardium. We investigated the hypothesis that statins, which have pleiotropic effects, augment the therapeutic potential of AdSCs and that AdSCs also act as drug delivery tools. Simvastatin-conjugated nanoparticles (SimNPs) significantly promoted migration activity without changing proliferation activity and upregulated growth factor gene expression in vitro. A small number of intravenously administered SimNP-loaded AdSCs (10,000 cells per mouse) improved cardiac function following myocardial infarction, inducing endogenous cardiac regeneration in the infarcted myocardium. The de novo regenerated myocardium was thought to be derived from epicardial cells, which were positive for Wilms’ tumor protein 1 expression. These findings were attributed to the sustained, local simvastatin release from the recruited SimNP-loaded AdSCs in the infarcted myocardium rather than to the direct contribution of recruited AdSCs to tissue regeneration. SimNP-loaded AdSCs may lead to a novel somatic stem cell therapy for IHDs. Stem Cells Translational Medicine 2019;8:1055–1067

The spleen is associated with inflammation, and the size of the spleen is affected by hemodynamic congestion and sympathetic stimulation. However, the association between splenic size and prognosis in patients with heart failure remains unknown. Between January 2015 and March 2017, we analyzed 125 patients with acute decompensated heart failure who were assessed by computed tomography (CT) on the day of admission. The spleen was measured by 3-dimensional CT and then the patients were assigned to groups according to their median splenic volume indexes (SpVi; splenic volume/body surface area). We then compared their baseline characteristics and rates of readmission for heart failure after one year. The median SpVi was 63.7 (interquartile range: 44.7-95.3) cm3/m2. Age did not significantly differ between the groups. Patients with a high SpVi had more significantly enlarged left atria and left ventricles. Multiple regression analysis identified significant positive correlations between SpVi and posterior wall thickness as well as left ventricular mass index. Kaplan-Meier analysis revealed lower event-free rates in the patients with a high, than a low SpVi (P = 0.041, log-rank test). After adjustment for potential cofounding factors, SpVi was independently associated with readmission for heart failure (Hazard ratio, 2.25; 95% confidence interval, 1.01-5.02; P = 0.047). In conclusion, increased splenic volume is independently associated with readmission for heart failure among patients with acute decompensated heart failure.

Patient: Female, 34-year-old Final Diagnosis: Left atrial appendage ostial stenosis Symptoms: No symptoms Medication:— Clinical Procedure: — Specialty: Cardiology Objective: Rare disease Background: Left atrial appendage (LAA) ostial stenosis is a rare cardiac condition usually identified by transesophageal echocardiography (TEE). LAA ostial stenosis can be classified into 2 types: one is idiopathic and the other is a complication after incomplete surgical LAA ligation. The former one is even rarer and only 12 cases have previously been reported. Case Report: An asymptomatic young woman was found at a medical checkup to have an abnormal jet signal in the left atrium on transthoracic echocardiography. TEE revealed that the abnormal signal originated from a narrowed orifice of the LAA. There were no other cardiac abnormalities in this woman. Unlike the previously reported cases, our case had LAA ostial stenosis detected by transthoracic echocardiography but not by TEE. Conclusions: We describe a case of anatomic narrowing of the LAA orifice in a young woman. This was a first-ever case of idiopathic LAA ostial stenosis that was detected by transthoracic echocardiography. Because of the very small number of such cases reported, it remains unknown whether anticoagulation is required to prevent intra-atrial thrombus formation.

Background Peak oxygen consumption (peak VO2) is a major prognostic parameter in heart failure (HF). Previous studies have shown a relationship between peak VO2 and impaired oxygen uptake and utilization in the peripheral muscles. The purpose of this study was to clarify the determinant of increased peak VO2 by cardiac rehabilitation (CR) in patients with HF. Methods We performed echocardiography during upright ramp bicycle cardiopulmonary exercise test in 30 HF patients (61±1 years of age, 80% male) before and 6 months after CR. HR reserve was determined as the change in HR from rest to peak exercise, expressed as a percentage of the predicted maximal HR reserve. Elastance index (EAI) and LV end-systolic elastance index (ELVI) were derived as the ratio of end-systolic pressure to stroke volume index and end-systolic volume index, respectively. End-systolic pressure was estimated from the equation 0.9 × brachial systolic blood pressure. Ventriculo-arterial coupling (VAC) was calculated as the quotient of EAI and ELVI. The ratio of LDEDVI to E/e' mean was used to evaluate LV diastolic compliance. Systemic vascular resistance index was calculated as mean arterial pressure divided by echocardiography calculated cardiac index and multiplied by 80. The arterial venous oxygen content difference (C (A-V) O2 gradient) was calculated by using the Fick equation as: VO2/echocardiography calculated cardiac output. Results Peak VO2 and C (A-V) O2 gradient were increased by CR. However, heart rate reserve, systolic reserve, VAC, diastolic reserve and vasodilation reserve were unchanged by CR (Table 1). Conclusions Increased oxygen uptake and utilization in the peripheral muscles, rather than cardiac function reserve, may be determinants of increased peak VO2 by CR in HF. Table 1 Funding Acknowledgement Type of funding source: None

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) levels using a statin is a cornerstone of preventive therapeutic management following acute myocardial infarction (AMI). In addition to its anti-atherosclerotic effects, recent studies reported a lower occurrence of heart failure (HF) under statin therapy. However, there is a wide variability in statin response. The association between the response to statin and the occurrence of HF in AMI subjects remains unclear. The purpose of present study is to examine whether the variability in statin response affects HF risk after AMI. METHODS: We analyzed 505 statin-naïve AMI subjects undergoing primary percutaneous coronary intervention (PCI) who commenced atorvastatin, rosuvastatin, or pitavastatin. Statin hyporesponse was defined as a reduction in LDL-C levels

Background B-type natriuretic peptide (BNP) has been widely used for the diagnosis of heart failure, its severity, and prognosis. However, little is known about factors related to disproportionately low BNP levels even during acute heart failure conditions. Methods and results Among 424 patients hospitalized for acute heart failure, we categorized the patients into the HFpEF (LVEF > 50%) or HFrEF (LVEF ≤ 50%) group and subdivided them into disproportionately low BNP (LB) group and high BNP (HB) group using a cut-off BNP level of 200 pg/mL at admission. The proportion of patients with LB was higher in the HFpEF group (22.2%) than in the HFrEF group (10.9%, p = 0.002). Patients with LB had a high BMI, lower blood pressure, and history of previous cardiovascular surgery in the HFpEF group, while patients in the HFrEF group had a high BMI and smaller left ventricular end-diastolic volume index. Furthermore, presence of LB in the HFrEF group was related to good prognosis, but LB in the HFpEF group was an indicator of poor prognosis as HB group. Conclusions The factors associated with LB were different between the HFpEF and HFrEF groups. LB was related to good prognosis in HFrEF, but not in HFpEF.

Objectives Cerebral microbleeds (CMBs), which can be detected by gradient-echo T2*-weighted magnetic resonance imaging (MRI), represent small chronic brain hemorrhages caused by structural abnormalities in cerebral small vessels. CMBs are known to be a potential predictor of future stroke, and are associated with age, various cardiovascular risk factors, cognitive impairment, and the use of antithrombotic drugs. Patients with coronary artery disease (CAD) are at potentially high risk of CMBs due to the presence of coexistent conditions. However, little is known about CMBs in patients with CAD. We aimed to identify the factors associated with the presence of CMBs among patients with CAD. Methods We evaluated 356 consecutive patients [mean age, 72 ± 10 years; men = 276 (78%)] with angiographically proven CAD who underwent T2*-weighted brain MRI. The brain MRI was assessed by researchers blinded to the patients’ clinical details. Results CMBs were found in 128 (36%) patients. Among 356 patients, 119 (33%) had previously undergone percutaneous coronary intervention (PCI), and 26 (7%) coronary artery bypass grafting (CABG). There was no significant relationship between CMBs and sex, hypertension, dyslipidemia, diabetes mellitus, anticoagulation therapy, antiplatelet therapy, or prior PCI. CMBs were significantly associated with advanced age, previous CABG, eGFR, non-HDL cholesterol, carotid artery disease, long-term antiplatelet therapy, and long-term dual antiplatelet therapy (DAPT) using univariate logistic regression analysis. The multivariate logistic regression analysis showed that long-term antiplatelet therapy (odds ratio, 1.73; 95% CI, 1.06 – 2.84; P = 0.03) or long-term DAPT (odds ratio, 2.92; 95% CI, 1.39 – 6.17; P = 0.004) was significantly associated with CMBs after adjustment for confounding variables. Conclusions CMBs were frequently observed in patients with CAD and were significantly associated with long-term antiplatelet therapy, especially long-term DAPT.

Patient: Male, 46 Final Diagnosis: Eosinophilic granulomatosis with polyangiitis Symptoms: Chest pain Medication: — Clinical Procedure: Skin biopsy Specialty: Cardiology Objective: Rare co-existance of disease or pathology Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis of unknown cause accompanied by prominent eosinophilia. Intracardiac thrombosis is one of the major cardiac complications in EGPA that may cause thromboembolism. Case Report: A 46-year-old male presenting with intermittent chest pain and numbness of the lower extremities was admitted to our center. His case was complicated by multiple brain infarcts and endocardial thrombosis in the left ventricle. A condition of restrictive cardiomyopathy was also found. After a thorough workup, he was diagnosed with antineutrophil cytoplasmic antibody (ANCA) positive EGPA. Interestingly, the thrombus was accompanied by a pressure gradient producing mid-ventricular obstruction. The patient improved reasonably with immunosuppression and anticoagulation treatment, in addition to heart failure treatment, and had a concomitant regression of the thrombus and reduction of the pressure gradient. Conclusions: For an EGPA patient complicated by intraventricular obstruction caused by endocardial thrombosis, which could accelerate the release of the thrombus into the systemic circulation resulting in a life-threating condition, timely and aggressive measures against cardioembolic complications should be considered.

Background Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).Methods and Results:A total of 44 patients diagnosed with AMI were included in the current study. All patients underwent emergency percutaneous coronary intervention (PCI). The median of peak creatine kinase (CK) and CKMB values was 1,816 U/L and 159 U/L, respectively. Serum levels of FGF23, calcium, and inorganic phosphate (iP) were measured before PCI, and on days 1, 3, 5, 7 after PCI. Serum FGF23 levels showed a slight, but significant decrease on days 1 and 3 after PCI, and a 1.5- and 2.0-fold increase on days 5 and 7, respectively, after PCI. As compared with propensity score-matched patients without AMI, serum FGF23 was significantly lower among the current cohort of AMI patients. In 22 subjects who underwent a follow-up echocardiographic examination at 6 months after the onset of AMI, the log-transformed relative increase in FGF23 on day 7 significantly and negatively correlated with changes between LVEF on admission and that at 6 months afterward. Conclusions After a slight decrease on days 1 and 3 after admission, serum FGF23 increased significantly on days 5 and 7. The underlying mechanism and potential clinical importance of these observations require further investigation.

Background: Circulating soluble urokinase-type plasminogen activator receptor (suPAR), which can reflect immune activation and low-grade inflammation, may be a novel biomarker of cardiovascular disease. Methods: We investigated the potential association between suPAR and the prevalence of atrial fibrillation (AF) by analyzing patients with either sinus rhythm, paroxysmal atrial fibrillation (PAF), or non-paroxysmal atrial fibrillation (NPAF), which indicates either permanent or persistent AF. Results: Among 426 patients enrolled (mean age 71.4±9.2 years; 110 (25.8%) female), 310, 62, and 54 were diagnosed with sinus rhythm, PAF, and NPAF, respectively. NPAF was >10-fold more prevalent in the highest suPAR quartile (>3534 pg/mL; 32 (30.2%) of 106 patients) than in the lowest suPAR quartile (

Mean serum uric acid (SUA) levels are higher in men than women. In addition, recent studies have suggested that the SUA threshold at which the cardiovascular risk might increase may vary between women and men. In the current retrospective study, by analyzing the data from 219 female and 519 male patients who were free from uric acid-lowering medication, we investigated whether SUA is associated with left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), and plasma levels of B-type natriuretic peptide (BNP) independent of confounding factors, such as serum calcium, inorganic phosphate, and fibroblast growth factor 23 (FGF23), in a gender-specific manner.In multivariate stepwise linear regression analysis in which age, blood pressure, eGFR, corrected calcium, inorganic phosphate, and FGF23 were entered as potential covariates, SUA was selected as a factor significantly associated with LVEF, LVMI, and plasma levels of BNP in both genders. On the other hand, however, after adding diuretic use as a potential covariate, the association between SUA and LVEF lost statistical significance in both genders, and that between SUA and BNP lost significance among female patients. These findings suggest that diuretic use is a non-negligible confounder in understanding the observed association between SUA and cardiac dysfunction and heart failure.In summary, SUA is associated with left ventricular hypertrophy independent of confounding factors including FGF23 and diuretic use in female and male patients. Whether lowering SUA can influence the progression of cardiac remodeling awaits further investigation.

Background Heart failure (HF) is an epidemic in healthcare worldwide including Asia. It appears that HF will become more serious with aging of the population. The patients with heart failure and preserved ejection fraction (HFpEF) were older, more often female, and frequently have comorbidities including hypertension. However, lower systolic blood pressure (SBP) on admission is associated with poor outcomes in patients with HF. It remains unclear whether this association is similar in very elderly patients with HFpEF. Purpose To investigate clinical features and prognosis in octogenarian HFpEF subjects. Methods We analyzed 87 consecutive subjects aged 80 years or older who were hospitalized for acute decompensated HF with left ventricular ejection fraction (LVEF) ≥50% between 2015 and 2017. Clinical characteristics and a composite event of cardiac death and HF hospitalization were compared in two groups according to SBP cut-off of 140 mmHg on admission. Results The prevalence of lower SBP subjects (mean BP = 118 mmHg) and higher SBP (mean BP = 166 mmHg) subjects were 41.4% and 58.6%, respectively. Lower SBP subjects were more comorbid with atrial fibrillation (72.2 vs. 45.1%, p=0.01). In the lower SBP group, diuretics, mineralocorticoid receptor antagonists (MRA), beta-blockers and ACE inhibitors/ARBs were more commonly used than higher SBP group (Table). During the observational period (median = 1.0 year), lower SBP on admission was associated with a 2.65-fold [95% confidence interval (CI): 1.29–5.55, p=0.009] greater likelihood of experiencing the composite events of cardiac death and rehospitalization for HF (Figure). This observation was still consistent even after adjusting clinical demographics and comorbidity [hazard ratio = 2.95, 95% CI: 1.30–6.87, p=0.01]. Table 1 Lower SBP group (n=36) Higher SBP group (n=51) P-value Atrial fibrillation (%) 72.2 0.01 0.01 Loop diuretic (%) 97.1 83.7 0.08 MRA (%) 47.1 24.5 0.04 Beta-blocker (%) 52.9 44.9 0.51 ACE inhibitor/ARB (%) 59.2 29.4 0.01 Figure 1 Conclusions In octogenarian patients with acute decompensated HF and preserved LVEF, SBP on admission less than 140 mmHg is significantly associated with poor outcomes. Future studies need to prospectively evaluate optimal SBP treatment goals in very elderly patients with HFpEF.

Treatment involving the insertion of an implantable cardioverter defibrillator and cardiac resynchronization therapy devices has markedly improved the prognosis of cardiac sarcoidosis. However, the prognosis remains poor in patients with advanced cardiac dysfunction or heart failure. We herein report the clinical course and histopathological findings of the autopsied heart of a patient with cardiac sarcoidosis with long-term refractory heart failure.

The fibrosis-4 index (FIB-4 index) is a marker of liver fibrosis. It has been reported that the FIB-4 index in compensated phase is associated with estimated right-sided filling pressure and poor prognosis in patients with heart failure. However, the relationship with invasively obtained right-sided cardiac pressures has been unclear. Hemodynamic status was evaluated by right heart catheterization in 189 heart failure patients who were in a clinically compensated phase between January 2015 and September 2017. Patients were assigned to two groups based on a median FIB-4 index of 2.15, then hemodynamic parameters and event rates were compared. Endpoint was defined as a composite of all-cause death, readmission for heart failure, or left ventricular-assist device implantation. Then, we also investigated correlations between the FIB-4 index and clinical factors, including hemodynamic parameters. Patients with a high FIB-4 index were significantly older (76 [IQR, 63–80] vs. 65 [IQR, 56–74] years, P

We reported a 67-year-old woman in whom large atrial thrombi were found by chance during discontinuation of therapeutic anticoagulation. The patient, with a history of mitral valve replacement surgery, had stopped anticoagulation for months because of intractable gastrointestinal bleeding, during which she was found to have 3 large thrombi in the atria on transesophageal echocardiography: left atrial free-floating ball-shaped thrombus, left atrial appendage thrombus, and right atrial appendage thrombus. One month following diagnosis, she still had the free-floating thrombus despite adequate anticoagulation. Free-floating ball-shaped thrombus is a rare finding observed on echocardiography in patients with mitral valve disease and an even rarer finding in case of appendage thrombi coexisting.

BackgroundInfluenza virus infection (IVI) was reported to be associated with minor cardiac changes, mostly those detected on electrocardiogram with and without elevated blood markers of myocardial injury; however, the characteristics of myocardial involvement in association with IVI are poorly understood. This study used echocardiographic tissue imaging (tissue Doppler, strain, and strain rate) to evaluate changes in left atrial (LA) and left ventricular (LV) myocardial function after IVI.Methods and resultsWe examined 20 adult individuals (mean age, 43 years) at 2 and 4 weeks after diagnosis of IVI. For myocardial functional variables, we obtained LV global longitudinal strain (GLS), LV early diastolic strain rate (e'sr), LA strain, and LA stiffness (E/e'/LA strain), in addition to data on tissue Doppler (s', e', and a') and myocardial performance index. Blood markers of myocardial injury were also examined. During follow-up, there were no significant changes in global chamber function such as LV ejection fraction, E/e', and LA volume. However, significant changes in myocardial function were observed, namely, in s' (8.0 ± 1.6 cm/s to 9.3 ± 1.5 cm/s; p = 0.01), e' (10.2 ± 2.8 cm/s to 11.4 ± 3.0 cm/s; p < 0.001), e'sr (1.43 ± 0.44 1/s to 1.59 ± 0.43 1/s; p = 0.005), and LA strain (35 ± 8% to 40 ± 12%; p = 0.025), and the myocardial performance index (0.52 ± 0.20 to 0.38 ± 0.09; p = 0.009), but not in a', LA stiffness, or GLS. Cardiac troponin T and creatinine kinase isoenzyme MB were not elevated significantly at any examination.ConclusionsMyocardial dysfunction during IVI recovery appeared to be transient particularly in the absence of myocardial injury. Echocardiographic tissue imaging may be useful to detect subclinical cardiac changes in association with IVI.

Patients with chronic kidney disease (CKD) experiencing atrial arrhythmia are hypothesized to have elevated CHADS2 and CHA2DS2-VASc scores, thereby predisposed to left atrial (LA) thrombus formation and subsequent thromboembolism. We examined possible association of LA thrombogenic milieu (TM) with CKD in patients with nonvalvular atrial fibrillation. A total of 581 patients (181 women; mean age, 67 years) who underwent transesophageal echocardiography were examined. Patients were divided into 4 groups based on the estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2): eGFR ≥90 (n = 29), 60≤ eGFR

Background and Aims: Combination of Eicosapentaenoic Acid (EPA) and HMG-CoA reductase inhibitor (statin) are known to be an effective therapy for cardiovascular diseases, however, their biological roles in the favorable effect on adverse event have not been studied well. In this study, we aimed to investigate the effect of EPA and statins focusing on plaque formation in a rabbit plaque model. Methods: Rabbit carotid artery was injured with a balloon followed by feeding with a normal diet for 4 w and then with a high-cholesterol diet for 4 w. The rabbits were either received pitavastatin alone, EPA alone, combination (pitavastatin+EPA) or vehicle (control) for 4 w with a high-cholesterol diet. The injured carotid arteries were harvested and analysed morphometrically and immunohistochemically. Results: In control group, smooth muscle cells were located on the luminal side of the plaque and lipidrich macrophages accumulated in the center of the plaque expressing Matrix Metalloproteinase-9 (MMP-9), Tissue Factor (TF), and NF-kB, those are characteristic of unstable plaques. In contrast, EPA reduced the expression of TF and NF-kB and increased the expression of PPAR-α in the plaque. Pitavastatin also reduced the expression of MMP-9, TF, and NF-kB, but not PPAR-α in the plaque. Combination of pitavastatin and EPA significantly reduced the expression of MMP-9, TF, and NF-kB increasing the expression of PPAR-α resulting in the inhibition of intimal hyperplasia and plaque formation in carotid arteries. Conclusions: Pitavastatin and EPA synergistically played a role for inhibitory effect on plaque formation decreasing the expression of inflammation-related molecules and increasing the expression of PPAR-α in injured artery.

Aim Fibroblast growth factor 23 (FGF23) and α-Klotho have been recently identified to play a crucial role in calcium/phosphate metabolism. We herein investigated the possible relation between serum FGF23/α-Klotho levels and coronary artery calcification (CAC) and aortic valve calcification (AVC). Methods Among subjects with diagnosed or suspected coronary artery disease (CAD), CAC and AVC were estimated via the Agatston score of 320-detector computed tomography images, and serum FGF23 and α-Klotho levels were measured. Results In total, 157 subjects were enrolled (75 women and 82 men). We performed logistic regression using CAC as a dependent variable; the highest FGF23 tertile (＞ 52.5 pg/mL) was significantly positively associated with CAC with an odds ratio of 6.61 versus the lowest FGF23 tertile (＜ 35.3 pg/mL) in women after the adjustment for potential confounding variables including age, renal function, hypertension, statin use, diuretic use, and calcium/phosphate metabolism related factors. In addition, the highest α-Klotho tertile (＞ 561 pg/mL) was significantly associated with AVC with an odds ratio of 6.31 versus the lowest α-Klotho tertile (＜ 306 pg/mL) in men after adjusting for the same variables. On the other hand, the association between FGF23 and CAC/AVC in men or that between α-Klotho and CAC/AVC in women was nonsignificant. Conclusion Among subjects with diagnosed or suspected CAD, serum FGF23 was positively associated with CAC in women and serum α-Klotho was positively associated with AVC in men independent of the confounding variables, including the renal function and calcium/phosphate metabolism-related factors.

Background and purpose Xanthine oxidoreductase (XOR), which catalyzes purine catabolism, has two interconvertible forms, xanthine dehydrogenase and xanthine oxidase, the latter of which produces superoxide during uric acid (UA) synthesis. An association between plasma XOR activity and cardiovascular and renal outcomes has been previously suggested. We investigated the potential association between cardiac parameters and plasma XOR activity among cardiology patients. Methods and results Plasma XOR activity was measured by [13C2,15N2]xanthine coupled with liquid chromatography/triplequadrupole mass spectrometry. Among 270 patients who were not taking UA-lowering drugs, XOR activity was associated with body mass index (BMI), alanine aminotransferase (ALT), HbA1c and renal function. Although XOR activity was not associated with serum UA overall, patients with chronic kidney disease (CKD), those with higher XOR activity had higher serum UA among patients without CKD. Compared with patients with the lowest XOR activity quartile, those with higher three XOR activity quartiles more frequently had left ventricular hypertrophy. In addition, plasma XOR activity showed a U-shaped association with low left ventricular ejection fraction (LVEF) and increased plasma B-type natriuretic peptide (BNP) levels, and these associations were independent of age, gender, BMI, ALT, HbA1C, serum UA, and CKD stages. Conclusions Among cardiac patients, left ventricular hypertrophy, low LVEF, and increased BNP were significantly associated with plasma XOR activity independent of various confounding factors. Whether pharmaceutical modification of plasma XOR activity might inhibit cardiac remodeling and improve cardiovascular outcome should be investigated in future studies.

Attenuation correction using segmentation of scatter and photo-peak window data (SSPAC) enables an evaluation of the attenuation map in a patient-specific manner without additional radiation exposure. We compared the accuracy of SSPAC and non-corrected myocardial perfusion scintigraphy methods for diagnosing the number of stenosed coronary artery vessels. We retrospectively reviewed the data from 183 consecutive patients who underwent 99mTc-tetrofosmin stress/rest SPECT examination and a coronary angiography within 3 months. The MPS images were reconstructed with and without SSPAC attenuation correction. We examined the accuracy of the quantitative interpretation using summed differential score in the detection of coronary artery disease (CAD). The attenuation maps were successfully determined in 179 of 183 patients (98%). In terms of the vessel-based diagnostic ability, sensitivity, specificity, positive predictive and negative predictive values of the SSPAC and non-correction methods for diagnosing CAD in individual coronary territories were 77%*, 89%, 74%*, and 90%* vs 51%, 87%, 62%, and 82%, respectively (*P

Besides regulating calcium-phosphate metabolism, fibroblast growth factor-23 (FGF23) and Klotho have been proposed to have other roles in heart and vasculature. For example, FGF23 has been associated with cardiac hypertrophy and reduced left ventricular ejection fraction among patients with chronic kidney disease and cardiovascular disorders. The purpose of the study was to investigate whether serum FGF23 and α-Klotho concentrations are associated with cardiac diastolic dysfunction and related parameters among cardiac patients with preserved left ventricular ejection fraction. The current study enrolled 269 patients (69 women, 200 men) who were admitted to our cardiology department between October 2012 and January 2014 and had a left ventricular ejection fraction of >50%. Cardiac diastolic function was assessed by blood flow and tissue Doppler velocities, plasma B-type natriuretic peptide (BNP) concentration, and cardiac hypertrophy. After adjusting for sex, and age, logistic regression analysis showed that log(α-Klotho), but not log(FGF23), was significantly associated with diastolic dysfunction. After further adjustment for renal function, blood hemoglobin, and serum albumin levels, the negative association between log(α-Klotho) and diastolic dysfunction retained statistical significance with an odds ratio of 0.50 (95% confidence interval 0.31-0.81, P = 0.005, per 1 standard deviation). Among patients with preserved LVEF, serum α-Klotho concentrations were negatively associated with diastolic dysfunction. Whether modulation of serum levels α-Klotho will ameliorate cardiac diastolic function among patients with this disorder awaits further investigation.

Aim To study whether there is an association between serum immunoglobulin G4 (IgG4) concentration and cardiac function among cardiology inpatients. Methods This retrospective study included 91 patients who had sinus rhythm. Of 91 patients, 70 patients (77%) were aged ≥60 years (elderly group) and the remaining 21 patients (23%) were aged

Background The diagnosis of Immunoglobulin G4 (IgG4)-related disease (IgG4-RD), in general, depends on serum IgG4 concentrations and histopathological findings; therefore, diagnosis of IgG4-RD in cardiovascular organs/tissues is often difficult owing to the risk of tissue sampling. Methods Prevalence of IgG4-positive lymphoplasmacytic infiltration in 103 consecutive cardiovascular surgical samples from 98 patients with various cardiovascular diseases was analyzed immunohistochemically. Results The diagnoses of the enrolled patients included aortic aneurysm (abdominal, n = 8; thoracic, n = 9); aortic dissection (n = 20); aortic stenosis (n = 24), aortic regurgitation (n = 10), and mitral stenosis/regurgitation (n = 17). In total, 10 (9.7%) of the 103 specimens showed IgG4-positive cell infiltration with various intensities; five of these were aortic valve specimens from aortic stenosis, and IgG4-positive cell infiltration was present at >10 /HPF in three of them. In one aortic wall sample from an abdominal aortic aneurysm, various histopathological features of IgG4-RD, such as IgG4-positive cell infiltration, obliterating phlebitis, and storiform fibrosis, were observed. Conclusions IgG4-positive cell infiltration was observed in 9.7% of the surgical cardiovascular specimens, mainly in the aortic valve from aortic stenosis and in the aortic wall from aortic aneurysm. Whether IgG4-positive cell infiltration has pathophysiological importance in the development or progression of cardiovascular diseases should be investigated in future studies.

The role of pentraxin 3 (PTX3) has been implicated in the process of plaque vulnerability. However, few studies have addressed the direct relationship between plaque morphology and plasma PTX3. We evaluated the relationship between coronary vulnerable plaque, assessed by optical coherence tomography (OCT), and plasma PTX3 in patients with coronary artery disease (CAD).OCT was used to determine plaque vulnerability in 51 patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS; n = 17) and stable angina (SA; n = 34). Both highly-sensitive C-reactive protein and systemic plasma PTX3 were measured.Based on the OCT findings, patients were divided into 3 groups; a fibrous plaque (n = 18), thick-cap fibroatheroma (ThCFA) (n = 19), and thin-cap fibroatheroma (TCFA) (n = 14) groups. ThCFA was defined as a lipid-rich plaque (lipid content in ≥ 2 quadrant) covered with ≥ 65 μm thick fibrous cap, and TCFA was that with < 65 μm. There were no differences in patient characteristics between the 3 groups except for the presence of ACS and eicosapentaenoic acid levels. TCFA was more frequently observed with plaque rupture and intraluminal thrombus compared with the other 2 groups. Plasma PTX3 levels were higher in the TCFA group compared with the fibrous plaque and ThCFA groups, and showed weak correlation with cap thickness.Plasma PTX3 level was associated with plaque vulnerability assessed by OCT in patients with CAD.

Aim: The clinical relevance of the suggested pleiotropic effects of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) is controversial. Aggressive statins effectively reduce lipid levels, but whether their other effects are more powerful than those of regular statins is unknown.Methods: We enrolled 32 patients (mean age, 65 y; male, 23) who had undergone coronary revascularization over 6 months previously and whose serum LDL cholesterol levels persisted at >100 mg/dL, regardless of pravastatin (10 mg/day). Before and 1 and 6 months after switching to atorvastatin (10 mg/day), we evaluated lipid profiles, including RLP-C (remnant-like particle cholesterol), high sensitive CRP (hsCRP), soluble CD40 ligand (sCD40L), TBARS (thiobarbituric acid reactive substances), and endothelial function determined from flow-mediated dilation (FMD) of the brachial artery.Results: One month on atorvastatin lowered LDL cholesterol by 24% (131 to 100 mg/dL, p

Recent epidemiologic studies have suggested that serum dehydroepiandrosterone sulfate (DHEAS) levels have a significant inverse correlation with the incidence of cardiovascular diseases. However, direct evidence for the association with DHEAS and vascular disorders has not yet been explored. DHEAS significantly reduced neointima formation 28 days after surgery without altering other serum metabolite levels in a rabbit carotid balloon injury model. Immunohistochemical analyses revealed the reduction of proliferating cell nuclear antigen (PCNA) index and increase of TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) index, expressing differentiated vascular smooth muscle cell (VSMC) markers in the media 7 days after surgery. In vitro, DHEAS exhibited inhibitory effects on VSMC proliferation and migration activities, inducing G1 cell cycle arrest with upregulation of one of the cyclin dependent kinase (CDK) inhibitors p16(INK4a) and apoptosis with activating peroxisome proliferator-activated receptor (PPAR)-alpha in VSMCs. DHEAS inhibits vascular remodeling reducing neointima formation after vascular injury via its effects on VSMC phenotypic modulation, functions and apoptosis upregulating p16(INK4a)/activating PPARalpha. DHEAS may play a pathophysiological role for vascular remodeling in cardiovascular disease.

Aim: Vascular or valvular calcification is a manifestation of atherosclerosis. The aim of this study was to clarify the association between calcification in the vascular or valvular area and significant coronary stenosis; that is, the requirements of coronary revascularization (CR), and to analyze the most associated marker among those valuables.Methods and Results: A total of 253 consecutive patients underwent multi-detector spiral computed tomography (MDCT) to diagnose coronary artery stenosis. We quantitatively and qualitatively analyzed calcification in vascular (coronary artery, thoracic ascending and descending aorta) and valvular (mitral and aortic valve) areas. Of 253 patients, 56 with suspected coronary artery stenosis or who had heavy calcification that precluded a diagnosis of lumen stenosis underwent selective coronary angiography. Coronary artery stenosis was significant in 47 patients, of whom 40 underwent CR. The calcification score revealed a significant association between any two sites. Univariate analysis revealed that CR patients showed significantly more calcification at sites other than the aortic valve and a significantly higher calcium score at 3 vascular beds. Multivariate analysis revealed that the presence of calcification in the ascending aorta and a calcium score > 103.8, a cut-off value determined by receiver-operating characteristics (ROC) curve analysis, for the coronary artery were independent factors for CR.Conclusions: Calcification at sites other than the aortic valve was significantly related to CR (+). The presences of calcification in the ascending aorta and a calcium score > 103.8 for the coronary artery were independently associated with CR.

Background Few data have existed on myocardial postsystolic shortening (PSS) accounting for left ventricular (LV) diastolic dysfunction in systemic hypertension. We examined this relationship, along with clinical and other cardiac parameters, in asymptomatic patients with hypertension. Methods We analyzed 104 patients on pharmacological treatment for hypertension who had no signs or symptoms of heart failure for conventional and speckle tracking echocardiography. The sum of the postsystolic index for multiple LV segments (total PSI) and global longitudinal strain (GLS) was computed and used as measures for global PSS and myocardial systolic function, respectively. The tissue Doppler e’ and the speckle tracking–derived global strain rate during early diastole (e'sr) were obtained as indicators of LV relaxation. The circumferential end-systolic stress was also determined noninvasively and substituted for a measure of myocardial afterload. Results Main variables that correlated with the e’ and e'sr were shown to be age, LV mass index, left atrial volume index, GLS, and the total PSI. Multivariate analysis including gender, circumferential end-systolic stress, and the use of calcium channel blockers as possible covariates revealed that age (β = −0.29, P = 0.002), total PSI (β = −0.26, P = 0.008), and LV mass index (β = −0.25, P = 0.017) were significant independent determinants of e’ and that age (β = −0.34, P

Background Atrial fibrillation (AF) occurs more frequently among patients with renal dysfunction. We investigated the possible association between prevalence of AF and serum fibroblast growth factor 23 (FGF23), which has been shown to be increased in subjects with renal dysfunction. Methods and results Among the total enrollment of 851 cardiac patients, 188 patients had AF (paroxysmal AF, 95; non-paroxysmal AF, 93). Prevalence of AF for FGF23 octile had a U-shaped relationship with the lowest prevalence at the fifth octile. On logistic regression analysis, when the third FGF23 quartile was used as the reference, the first and fourth FGF23 quartiles were associated with prevalence of AF with an odds ratio (OR) of 3.34 (95% confidence interval [CI]: 1.89-5.88) and 2.58 (95% CI: 1.45-4.58), respectively, after adjusting for confounding factors including estimated glomerular filtration rate (eGFR). Among the subgroup of 416 patients for whom serum parathyroid hormone and 25-hydroxy vitamin D data were available, OR of the first and the fourth FGF23 quartile were calculated to be 3.52 and 2.97, respectively, when further adjusted for these two variables in the statistical model. Conclusions Serum FGF23 had a U-shaped relationship with prevalence of AF among Japanese cardiac patients, which was independent of other calcium/phosphate metabolism-related parameters and eGFR. Pathophysiology underlying the observed link, if at all, awaits further investigation.

Background Previous reports indicate that D-dimer testing (DT) for acute aortic dissection (AAD) has a sensitivity of 100%, but each study comprised less than 30 patients. The aim of this study was to evaluate the positive rate and factors related to the results of DT for AAD in a larger population. Methods and Results DT (cutoff; upper normal limit) was performed for 113 consecutive AAD patients within 24 h of symptom onset. In total, 104 (92%) patients exhibited positive DT. The positive rate of DT showed a low tendency in patients aged less than 70 years and for a time interval from symptom onset to admission within 120 min, and there were significant differences between those with and without a thrombosed false lumen (TFL) (86.4% (n=59) vs 98.1% (n=54), p=0.033), complete TFL (excluding patients with ulcer-like projection (ULP) from those with a TFL) (81.1% (n=37) vs 97.4% (n=76), p=0.005) and length score (1 (n=28); 78.6%, 2 (n=40); 95.0%, 3 (n=45); 97.8%, p=0.005). Multivariate analysis demonstrated age (odds ratio =1.164, p=0.013), complete TFL (0.048, 0.030) and length score (6.271, 0.033) as independent factors. Conclusions Physicians should be aware that younger patients with short dissection length and a TFL without ULP are liable to have false-negative DT results. (Circ J 2006; 70: 1598 - 1601)

Background It is important to rapidly distinguish patients with acute aortic dissection of the ascending aorta (AADa) from those with acute myocardial infarction (AMI), because minimizing the time to initiation of reperfusion therapy leads to maximum benefits for AMI and erroneous reperfusion therapy for AADa can produce harmful outcomes. The aim of this study was to find a simple test to distinguish such patients. Methods and results Data were collected from 29 consecutive patients with AADa and 49 consecutive patients with AMI who were admitted within 4 h of the onset of symptoms. The D-dimer concentration and the ratio of the maximum upper mediastinal diameter to the maximum thoracic diameter on plain chest radiograph (M-ratio) in the emergency room were studied retrospectively. Setting the cutoff values of the D-dimer concentration and the M-ratio to 0.8 or 0.9 microg/ml and 0.309, respectively, gave a sensitivity of 93.1% and 93.1% for AADa, respectively, and a sensitivity of 91.8% and 85.7% for AMI, respectively. Conclusions The D-dimer value and the M-ratio, with appropriate cutoff values, have potential as tests that can be routinely used to exclude AADa patients from patients diagnosed with AMI prior to reperfusion therapy.

In the human coronary arteries, the intima begins to thicken from early adolescence and shows progressive thickening with age. We compared the response to vascular injury of the coronary and femoral arteries using a canine model. Both incorporation of 5-bromo-2'-deoxyuridine (BrdU) and neointimal formation after balloon injury were significantly greater in the coronary artery than in the femoral artery. Also, the proliferative and migratory activities of coronary smooth muscle cells (SMCs) were significantly greater than those of femoral SMCs in vitro. The level of phosphorylated myosin light chain (phospho-MLC) was higher in coronary SMCs than in femoral SMCs. Y-27632, a specific inhibitor of Rho-kinase, significantly inhibited the PDGF-induced migration of both coronary and femoral SMCs. In contrast, the migration of coronary SMCs, but not femoral SMCs, was inhibited by ML-9, a specific inhibitor of myosin light chain kinase (MLCK). These findings suggest that the contribution of Rho-kinase and MLCK differs between the different arteries. They also suggest that a neointima develops more easily in the coronary artery than in the femoral artery because of the greater proliferative and migratory activity of coronary SMCs. Differential activation of MLC might partly explain the increased proliferation and migration of coronary SMCs.

Acute coronary syndrome occurred in 2 young adults who had a history of Kawasaki disease (KD), but few other coronary risk factors. The first patient was a 27-year-old male with acute myocardial infarction without stenosis detected by coronary arteriography 4 years earlier. Emergency coronary arteriography showed occlusion of the right coronary artery. Aspiration-thrombectomy and rescue balloon angioplasty were successfully performed. The second patient was a 32-year-old male with unstable angina. Right coronary arteriography showed total occlusion with severe calcification. Left coronary arteriography showed 99% stenosis at the proximal site of the circumflex artery, and a directional coronary atherectomy was performed. Histological examination of a specimen from this site revealed a lipid core, macrophages, and smooth muscle cells. Restenosis was not observed on follow-up coronary arteriography after 5-6 months in either case. The coronary stenosis in each case was probably caused by accelerated atherosclerosis at the site without aneurysm as it seemed to be 'normal' on arteriography. Conventional catheter intervention was effective treatment. The sequelae of KD should be recognized as independent coronary risk factors.

Introduction: Purpose: Serum concentrations of fibroblast growth factor-23 (FGF23) are increased in response to elevated serum phosphate levels among patients with renal dysfunction. Besides regulating circulating phosphate levels, FGF23 may induce cardiac hypertrophy; thus, enhanced FGF23 excretion may underlie the heart failure observed among patients with chronic kidney disease (CKD). Here we examined whether FGF23 concentrations are associated with cardiac hypertrophy among cardiac patients regardless of the presence or absence of CKD. Methods: The present study enrolled 480 cardiac patients admitted to our cardiology department between January 2012 and December 2012. Serum FGF23 level was measured by an ELISA method. Left ventricular mass index (LVMI) was used as a marker of cardiac hypertrophy. Results: Of the 480 patients, 132 (27.5%) had an estimated glomerular filtration rate (eGFR) of Conclusions: Among cardiac patients, serum FGF23 concentration was associated positively with left ventricular mass and negatively with left ventricular ejection fraction not only in patients with CKD, but also in those without CKD.