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Although percutaneous coronary intervention (PCI) has been the mainstay of revascularization strategy for significant coronary artery disease, future cancer risk after PCI has never been explored. We aimed to investigate the risk of incident cancer in patients undergoing PCI for the first time.We studied 125,613 patients who underwent the first PCI between 2010 and 2015 without a prior history of cancer. For comparison, we selected 628,065 age- and sex-matched controls without any history of cancer or PCI who completed the assigned national health examination during the same period.During a median 4.56 years (interquartile range, 3.06-6.13 years), 8528 patients from the PCI group and 40,166 controls were newly diagnosed with cancer (incidence rate, 15.1 vs. 13.9 per 1000 person-years, p 0.0001). Patients undergoing PCI presented a higher risk for cancer development than the controls in multivariable Cox analysis (adjusted HR [aHR] 1.06, 95% CI 1.04-1.09, p 0.0001). To minimize potential surveillance bias, we performed 1-year lag analysis by eliminating participants who developed cancer within 1 year from the PCI. In this analysis, the increased risk of overall cancer in the PCI group became insignificant (aHR 1.02, 95% CI 0.99-1.05, p = 0.2017). Regarding site-specific cancers, however, the risk of lung and hematologic malignancies remained higher and the risk of gastrointestinal, liver/biliary/pancreas, thyroid, and breast cancers remained lower in the PCI group.Differential future cancer risks were observed in patients undergoing PCI. The results suggest that specialized surveillance strategy might be warranted for this expanding population.

Temporal trends of the prevalence and incidence of hypertrophic cardiomyopathy (HCM) have not been well established in Asian populations. Using the Korean National Health Insurance Services database, we identified patients with a confirmed diagnosis of HCM between 2010 and 2016. The annual prevalence and incidence of HCM, and their clinical characteristics were investigated. The prevalence of HCM has increased from 0.016% (n = 6313) in 2010 to 0.031% (n = 13,035) in 2016. During a 7-year period, 13,229 patients were newly diagnosed with HCM. The incidence rate increased from 4.15 (per 100,000 person-years) in 2010 to 5.6 in 2016. The prevalence and incidence of HCM increased with age and peaked during the 70s, with male predominance in all age groups. Chest pain is the most frequent clinical presentation followed by shortness of breath and syncope. Hypertension and dyslipidemia were the two most common comorbidities. Heart failure and atrial fibrillation was diagnosed in about 1/3 and 1/4 of patients with HCM, respectively. The prevalence and incidence of HCM gradually increased from 2010 to 2016, possibly due to heightened recognition of the disease. Given the progressively high incidence of HCM with age and high prevalence of coexisting modifiable risk factors, continued efforts are required to increase awareness regarding HCM-related symptoms and potential complications.

Additional file 1: Table S1. Comparison of baseline clinical characteristics of patients who died versus survived after transplantation Table S2. Comparison of baseline echocardiographic and electrocardiographic parameters of patients who died versus survived after transplantation. Table S3. Comparison of baseline cardiac magnetic resonance parameters of patients who died versus survived after transplantation.

Additional file 1. Additional tables and figures.

Lower body mass index (BMI) is considered a poor prognostic factor in patients with heart failure (HF). We aimed to investigate the clinical impact of BMI on the risk of mortality in patients with acute HF (AHF) across various phenotypes.We retrospectively identified 4,146 registry patients with AHF and BMI data. The study population was categorized according to the WHO Asia-Pacific BMI classification: BMI18.5 kg/mDuring a median follow-up of 32 months, 1,732 patients (41.8%) died. Compared to patients with obesity II, those with overweight, ideal BMI or underweight status had a higher risk of mortality (overweight: hazard ratio [HR], 1.606; 95% confidence interval [CI], 1.016-2.539; p=0.042) (ideal BMI: HR, 1.744; 95% CI, 1.112-2.734; p=0.015) (underweight: HR, 2.729; 95% CI, 1.686-4.417; p0.001). Higher risk of mortality among patients with lower BMI was observed regardless of age, sex, hypertension, diabetes, ischemic heart disease, atrial fibrillation, and HF phenotype. Furthermore, low muscle index (total muscle mass/heightA lower BMI is associated with a higher risk of mortality in patients with AHF. This obesity paradox is observed in AHF regardless of comorbidities and HF phenotype.

Hypertrophic cardiomyopathy (HCM) is one of the most common inheritable cardiomyopathies. Contemporary management strategies, including the advent of implantable cardioverter-defibrillators and effective anticoagulation, have substantially improved the clinical course of HCM patients; however, the disease burden of HCM is still high in Korea. Sudden cardiac death (SCD), atrial fibrillation and thromboembolic risk, dynamic left ventricular outflow tract (LVOT) obstruction, and heart failure (HF) progression remain important issues in HCM. SCD in HCM can be effectively prevented with implantable cardioverter-defibrillators. However, appropriate patient selection is important for primary prevention, and the 5-year SCD risk score and the presence of major SCD risk factors should be considered. Anticoagulation should be initiated in all HCM patients with atrial fibrillation regardless of the CHA

Although proteinuria is a well-known risk factor for cardiovascular disease, its relationship with the progression of aortic stenosis (AS) has not been established. Our aim was to investigate the relationship between proteinuria (detected by urine dipstick test) and AS progression (assessed by the annualized reduction rate of aortic valve area [AVA]). A total of 460 patients with mild to moderate AS (defined by a peak velocity of 2.0–4.0 m/s) without end-stage renal disease who underwent two echocardiograms at least 3 months apart were included. The progression of AS was significantly faster in patients with proteinuria than those without (108 patients vs. 352 patients; annualized reduction rate of AVA, − 7.7 ± 13.5% vs. − 4.5 ± 11.6%; p = 0.017). The relationship between the presence of proteinuria and the accelerated progression of AS was significant among patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (− 11.0 ± 17.5% vs. − 4.2 ± 10.0%; p

Isolated cardiac sarcoidosis is a generally accepted disease condition, and the low yield of endomyocardial biopsy because of patchy involvement is also well known. However, current guidelines still require histologic confirmation of granuloma for the diagnosis of cardiac sarcoidosis, either in myocardial or extra-cardiac tissues. Therefore, only a presumptive diagnosis of chronic multifocal myocarditis of unknown origin can be made in a large number of patients in whom the only considerable diagnosis is cardiac sarcoidosis based on current knowledge. Even if these patients are treated with the same treatment scheme as that for cardiac sarcoidosis, which may not cause harm in the absence of a definite diagnosis, the true spectrum of cardiac sarcoidosis could not be determined for deciding the optimal treatment strategy. In addition, the current recommendations for dose, duration of initial steroid therapy, and treatment in patients who did not respond to initial steroid therapy are not easy to follow in real-world practice. We would like to propose a scoring system for the diagnosis of cardiac sarcoidosis and suggest our adoption or modification of the diverse current recommendations.

We investigated whether global longitudinal strain (GLS) is a better predictor of clinical events after surgery for mitral regurgitation (MR) than conventional parameters.The optimal timing for surgery is guided by left ventricular (LV) dimension or left ventricular ejection fraction (LVEF), even though normal LVEF can mask depressed LV systolic function in severe mitral MR.From 2006 to 2016, 506 patients (age 58.5 ± 13.7 years, 54.3% male) with severe primary MR who underwent mitral valve surgery were included. We measured GLS and global circumferential strain. Cardiac events included admission for worsening heart failure (HF), reoperation for failure of MV surgery, and cardiac death.During a median follow-up period of 3.5 years, 56 (11.1%) patients died, 41 (8.1%) were hospitalized for HF, and 10 (2.0%) underwent reoperation. In univariate analysis, LVEF, atrial fibrillation, left atrial dimension, age, previous ischemia, concomitant coronary artery bypass graft, and both GLS and global circumferential strain were predictive of cardiac events. On multivariate Cox models, age (hazard ratio [HR]: 1.429, 95% confidence interval [CI]: 1.116 to 1.831; p = 0.005), left atrial dimension (HR: 1.034, 95% CI: 1.006 to 1.063; p = 0.019) and GLS (HR: 1.229, 95% CI: 1.135 to 1.331; p 0.001) were independent predictors of cardiac events. In subgroup analysis, LV GLS was a significant predictor of cardiac outcome, regardless of the presence of LV dysfunction, the presence of atrial fibrillation, and the type of surgery. Impaired GLS was associated with all-cause mortality (HR: 1.068, 95% CI: 1.003 to 1.136; p = 0.040).GLS appears to be a better predictor of cardiac events all-cause death than conventional parameters. Measuring preoperative GLS is helpful to predict post-operative outcome and determine optimal timing for surgery in patients with severe primary MR.

Background While coronary computed tomography angiography (CCTA) provides comprehensive anatomic evaluation of coronary artery disease (CAD) with prognostic implications, clinically, the focus is usually placed on presence or absence of functionally significant CAD. Herein, we aimed to suggest a new risk stratification strategy using CCTA in patients with anatomic CAD but without myocardial ischemia on single-photon emission computed tomography (SPECT). Methods Consecutive patients (n = 798) with CAD on CCTA who underwent SPECT for evaluation of myocardial ischemia were retrospectively evaluated. The primary outcome was the occurrence of adverse cardiac events, including cardiac death, nonfatal myocardial infarction, unstable angina, and late revascularization. Results Of the enrolled patients, 542 (68%) showed no perfusion defect (PD) on SPECT. During the follow-up (median, 22.6 months), adverse cardiac events occurred in 23 patients without PD (4.6%). Presence of plaque in ≥4 coronary segments, plaque in the left main or proximal left anterior descending coronary artery, and partially calcified plaque presence were independent predictors of adverse events. When we defined the CCTA score based on these 3 predictors (0–3 points), the annualized event rates increased with increasing CCTA scores. Patients with a CCTA score of 3 were associated with a 23-fold risk increase (adjusted HR 23.18; p = 0.003) and showed unfavorable event-free survival, comparable to those with PD on SPECT (p = 0.191). Conclusion Anatomic CAD patients without evidence of myocardial ischemia on SPECT but with high-risk characteristics on CCTA showed unfavorable outcomes, comparable to those with PD. CCTA allows further risk stratification even in patients with negative SPECT findings.

The aim of this study was to evaluate whether native T1 value of the myocardium on cardiac magnetic resonance (CMR) could predict clinical events in patients with significant aortic stenosis (AS).Although previous studies have demonstrated the prognostic value of focal fibrosis using late gadolinium enhancement (LGE) by CMR in AS patients, the prognostic implication of diffuse myocardial fibrosis by noninvasive imaging remains unknown.A prospective observational longitudinal study was performed in 127 consecutive patients with moderate or severe AS (68.8 ± 9.2 years of age, 49.6% male) and 33 age- and sex-matched controls who underwent 3-T CMR. The degree of diffuse myocardial fibrosis was assessed by noncontrast mapping of T1 relaxation time using modified Look-Locker inversion-recovery sequence, and the presence and extent of LGE were also evaluated. The AS patients were divided into 3 groups by the native T1 value. Primary endpoint was a composite of all-cause death and hospitalization for heart failure.Native T1 value was higher in AS patients, compared with control subjects (1,232 ± 53 ms vs. 1,185 ± 37 ms; p = 0.008). During follow-up (median 27.9 months), there were 24 clinical events including 9 deaths (6 pre-operative and 3 post-operative), the majority of which occurred in the patients in the highest T1 tertile group (2.4% vs. 11.6% vs. 42.9% for lowest, mid-, and highest tertile groups; p 0.001 by log-rank test). The total number of events for both pre- and post-operative events also occurred more frequently in patients in the highest T1 tertile group. EuroSCORE II, the presence and/or extent of LGE, and the native T1 value were predictors of poor prognosis (adjusted hazard ratio for every 20-ms increase of native T1: 1.28; p = 0.003). In particular, the highest native T1 value provided further risk stratification regardless of the presence of LGE.High native T1 value on noncontrast T1 mapping CMR is a novel, independent predictor of adverse outcome in patients with significant AS.

Objectives This study sought to investigate the prognostic significance of left ventricular (LV) mass and geometry in ischemic stroke survivors, as well as the LV geometry–specific differences in the blood pressure–mortality relationship. Background LV mass and geometry are well-known prognostic factors in various populations; however, there are no data on their role in ischemic stroke patients. Methods We prospectively recruited 2,328 consecutive patients admitted with acute ischemic stroke to our institute between 2002 and 2010. Of these, 2,069 patients were analyzed in whom echocardiographic data were available to assess LV mass and geometry. Results All-cause mortality was significantly greater in patients with concentric hypertrophy (adjusted hazard ratio [HR]: 1.417; 95% confidence interval [CI]: 1.045 to 1.920) and concentric remodeling (HR: 1.540; 95% CI: 1.115 to 2.127) but nonsignificantly in those with eccentric hypertrophy (HR: 1.388; 95% CI: 0.996 to 1.935) compared with normal geometry in multivariate analyses. Relative wall thickness was a significant predictor of all-cause mortality (HR: 1.149 per 0.1-U increase in relative wall thickness; 95% CI: 1.021 to 1.307), whereas LV mass index was not (HR: 1.003 per 1 g/m2 increase in LV mass index; 95% CI: 0.999 to 1.007). Similar results were observed with cardiovascular mortality. In multivariable fractional polynomials, patients with altered LV geometry showed reverse J-curve relationships between acute-phase systolic blood pressure and all-cause or cardiovascular mortality, with the highest risks in the lower extremes, whereas those with normal geometry did not. Conclusions Echocardiographic assessment of LV geometry provided independent and additive prognostic information in ischemic stroke patients. A reverse J-shaped relation of mortality with blood pressure was found in patients with abnormal LV geometry.

Background Previous studies suggested that phosphodiesterase 5 inhibitors (PDE5i) have a beneficial effect in patients with heart failure (HF), although the results were inconsistent. We performed a meta-analysis to evaluate the effect of PDE5i in HF patients, and investigated the relationship between PDE5i effects and pulmonary hemodynamics. Method We searched PubMed, EMBASE and the Cochrane Library for randomized controlled trials (RCTs) that compared PDE5i with placebo in HF with reduced ejection fraction (HFrEF) or HF with preserved EF (HFpEF). PDE5i effects were interpolated according to baseline pulmonary arterial pressure (PAP) or according to changes in PAP after PDE5i treatment. Results Thirteen RCTs enrolling 898 HF patients, and two sub-analysis studies with different study outcomes, were included in the meta-analysis. Among patients with HFrEF, PDE5i improved peak VO2 (mean difference [MD], 3.76 mL/min/kg; 95% confidence interval [CI], 3.27 to 4.25; P

Objectives Congenital absence of the pericardium (CAP) is often confused with other conditions presenting with right ventricular dilatation and usually warrants CT or cardiac MR (CMR) to confirm. It would be desirable to have more specific echocardiographic criteria to provide a conclusive diagnosis. Methods 11 patients who were diagnosed with CAP (four patients with total CAP) based on CT/CMR were consecutively enrolled. Thirteen patients with atrial septal defect (ASD) and 16 normal subjects served as controls. To investigate spatial changes of heart in the thoracic cavity in CAP, following echocardiographic measurements were made in the left and right decubitus positions: the angle between the ultrasound beam and the left ventricular posterior wall (Angle-PW) in end-diastole at the parasternal long axis, and the distance between the chest wall and the most distal part of the left ventricular posterior wall (Distance-PW) at the parasternal mid-ventricular short axis. Results Angle-PW in patients with CAP were significantly greater than in those with ASD (100.1±12.5° vs 74.5±8.6°, p Conclusions Patients with CAP have dynamic alteration in cardiac position depending on posture, which is not observed in ASD or in normal controls. Hence, total or left-sided CAP can be reliably diagnosed with positional changes during routine echocardiography.

BACKGROUND It is important to understand the distribution of 2-dimensional strain values in normal population. We performed a multicenter trial to measure normal echocardiographic values in the Korean population. METHODS This was a substudy of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL) study. Echocardiographic specialists measured frequently used echocardiographic indices in healthy people according to a standardized method at 23 different university hospitals. The strain values were analyzed from digitally stored images. RESULTS Of a total of 1003 healthy participants in NORMAL study, 2-dimensional strain values were measured in 501 subjects (265 females, mean age 47 ± 15 years old) with echocardiographic images only by GE echocardiographic machines. Interventricular septal thickness, left ventricular (LV) posterior wall thickness, systolic and diastolic LV dimensions, and LV ejection fraction were 7.5 ± 1.0 mm, 7.4 ± 1.0 mm, 29.9 ± 2.8 mm, 48.9 ± 3.6 mm, and 62 ± 4%, respectively. LV longitudinal systolic strain (LS) values of apical 4-chamber (A4C) view, apical 3-chamber (A3C) view, apical 2-chamber (A2C) view, and LV global LS (LVGLS) were -20.1 ± 2.3, -19.9 ± 2.7, -21.2 ± 2.6, and -20.4 ± 2.2%, respectively. LV longitudinal systolic strain rate (LVLSR) values of the A4C view, A3C view, A2C view, and LV global LSR (LVGLSR) were -1.18 ± 0.18, -1.20 ± 0.21, -1.25 ± 0.21, and -1.21 ± 0.21-s, respectively. Females had lower LVGLS (-21.2 ± 2.2% vs. -19.5 ± 1.9%, p < 0.001) and LVGLSR (-1.25 ± 0.18-s vs. -1.17 ± 0.15-s, p < 0.001) values than males. CONCLUSION We measured LV longitudinal strain and strain rate values in the normal Korean population. Since considerable gender differences were observed, normal echocardiographic cutoff values should be differentially applied based on sex.

Background: The association of lifetime exposure to endogenous sex hormone with incident atrial fibrillation (AF) and subsequent ischemic stroke has never been studied. Methods: This study involved 4 638 299 natural postmenopausal waomen aged ≥40 years without prior history of AF and with national breast cancer check-up between January 1, 2009 and December 31, 2014. The primary end point was incident AF, and the secondary end point was subsequent ischemic stroke once AF has developed. Cox proportional hazard regression analysis was used to estimate the risk of end points. Results: During the mean follow-up of 6.3 years, shorter total reproductive years (P -for-trend P -for-trend Conclusions: In women with natural menopause, shorter lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. Paradoxically, prolonged exogenous hormone replacement therapy increased the risk of incident AF.

Background and Purpose— Hypertrophic cardiomyopathy patients with atrial fibrillation are at increased risk of stroke, and anticoagulation is strongly recommended. However, limited data are available regarding the safety and effectiveness of non–vitamin K antagonist oral anticoagulants (NOACs) for primary prevention of stroke. Methods— Using the Korean Health Insurance Review and Assessment Service database, we identified 2397 patients with hypertrophic cardiomyopathy and nonvalvular atrial fibrillation on oral anticoagulation from 2013 to 2016 without history of ischemic stroke, intracranial hemorrhage (ICH), or gastrointestinal bleeding (992 on warfarin and 1405 on NOACs). Inverse probability of treatment weighting with propensity scores was used to balance covariates between treatment groups. Risk for ischemic stroke, ICH, gastrointestinal bleeding, death, and their composite outcome associated with NOAC use was assessed with warfarin use as the reference. Results— During a mean follow-up of 1.6 years, the incidence rates of ischemic stroke, ICH, gastrointestinal bleeding, death, and composite outcome were all significantly lower in the NOAC than in the warfarin group (stroke, 2.8 versus 5.0; ICH, 0.5 versus 1.3; gastrointestinal bleeding, 2.3 versus 3.0; death, 3.0 versus 5.1; composite, 7.5 versus 12.5 events per 100 person-years). NOACs were associated with significantly lower risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.32–0.68), ICH (HR, 0.31; 95% CI, 0.14–0.69), gastrointestinal bleeding (HR, 0.62; 95% CI, 0.40–0.96), death (HR, 0.45; 95% CI, 0.31–0.65), and the composite outcome (HR, 0.48; 95% CI, 0.38–0.61) than warfarin. The same trend was observed regardless of the NOAC dose and across various high-risk subgroups. In analysis of individual NOACs, all NOACs were associated with lower risks of ischemic stroke and composite outcome. Conclusions— NOACs showed superior effectiveness and safety versus warfarin in the primary prevention of stroke versus warfarin in real-world Asian hypertrophic cardiomyopathy with atrial fibrillation.

Background Cardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation. Methods This study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19). Results CMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: − 24.2 ± 2.7% in cirrhosis vs − 18.6 ± 2.2% in healthy controls, P P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P P P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001). Conclusions Myocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.

Although hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has mortality rate as low as general population, previous studies have focused on identifying high-risk of sudden cardiac death. Thus, long-term systemic impact of HCM is still unclear. We sought to investigate the association between HCM and end-stage renal disease (ESRD). This was a nationwide population-based cohort study using the National Health Insurance Service database. We investigated incident ESRD during follow-up in 10,300 adult patients with HCM (age 62.1 years, male 67.3%) and 51,500 age-, sex-matched controls. During follow-up (median 2.8 years), ESRD developed in 197 subjects; 111 (1.08%) in the HCM, and 86 (0.17%) in the non-HCM (incidence rate 4.14 vs. 0.60 per 1,000 person-years, p p p

Aims To develop a mortality risk prediction model in patients with acute heart failure (AHF), using left ventricular (LV) function parameters with clinical factors. Methods and results In total, 4312 patients admitted for AHF were retrospectively identified from three tertiary centres, and echocardiographic parameters including LV ejection fraction (LV-EF) and LV global longitudinal strain (LV-GLS) were measured in a core laboratory. The full set of risk factors was available in 3248 patients. Using Cox proportional hazards model, we developed a mortality risk prediction model in 1859 patients from two centres (derivation cohort) and validated the model in 1389 patients from one centre (validation cohort). During 32 (interquartile range 13–54) months of follow-up, 1285 patients (39.6%) died. Significant predictors for mortality were age, diabetes, diastolic blood pressure, body mass index, natriuretic peptide, glomerular filtration rate, failure to prescribe beta-blockers, failure to prescribe renin–angiotensin system blockers, and LV-GLS; however, LV-EF was not a significant predictor. Final model including these predictors to estimate individual probabilities of mortality had C-statistics of 0.75 [95% confidence interval (CI) 0.73–0.78; P Conclusion We developed a mortality risk prediction model for patients with AHF incorporating LV-GLS as the LV function parameter, and other clinical factors. Our model provides an accurate prediction of mortality and may provide reliable risk stratification in AHF patients.

Background and aims Given the potential benefit of medical therapy in patients with non-obstructive coronary artery disease (CAD), there is a need for risk stratification and treatment strategy for these patients. We aimed to develop a risk prediction model for non-obstructive CAD patients for risk stratification and guidance of statin and aspirin therapy. Methods From a cohort of consecutive patients who underwent coronary computed tomography angiography (CCTA) (n = 25,087), we identified patients with non-obstructive CAD of 1–49% diameter-stenosis (n = 6243) and developed a risk prediction model for 5-year occurrence of a composite of all-cause mortality, myocardial infarction, and late coronary revascularization using a derivation cohort (n = 4391). Results Age, sex, hypertension, diabetes, anemia, C-reactive protein, and the extent of non-obstructive CAD were incorporated in the prediction model (risk score 0-13, C-index = 0.716). Patients were categorized into 4 groups; risk score of 0–3 (low-risk), 4-6 (intermediate-risk), 7-9 (high-risk), and ≥10 (very high-risk). Patients with very high-risk demonstrated unfavorable outcome comparable to patients with obstructive CAD. The low-risk group exhibited favorable outcome similar to those with no CAD. While statin therapy was associated with better outcomes in high- or very high-risk group (hazard ratio, 0.62; 95% confidence interval, 0.39–0.96; p = 0.033), aspirin use was associated with an increased risk in low-risk group (hazard ratio, 2.57; 95% confidence interval, 1.34–4.90; p = 0.004). Conclusions A dedicated risk scoring system for non-obstructive CAD using clinical factors and CCTA findings accurately predicted prognosis. According to our risk prediction model, statin therapy can be beneficial for high-risk patients, whereas aspirin can be harmful for low-risk patients.

Similar to left ventricular and aortic pressure waveforms, augmentation pressure (AugPr) in the right ventricular (RV) pressure waveform is also frequent in patients with pulmonary hypertension (PH). This study sought to evaluate whether the degree of AugPr in RV pressure waveform has prognostic value. Forty-one patients (13 men; mean age = 50.7 ± 16.1 years) with group 1 PH (mean pulmonary artery pressure [mPAP] ≥ 25 mmHg) who underwent cardiac catheterization as part of their work-up were retrospectively enrolled. Patients were divided into three groups. Group A: AugPr/RV systolic pressure < 25%; group B: AugPr/RV systolic pressure ≥ 25%; and group C: no discernible AugPr but showing peaked RV pressure waveform. Ten patients were included in group A (male-to-female ratio 3:7; mean age = 45.9 ± 12.1 years), 12 in group B (4:8, 53.8 ± 14.6 years), and 19 in group C (6:13, 51.8 ± 18.7 years). No differences in mPAP were seen between the three groups. Pulse pressure was significantly higher in group C compared to group A. Eight patients died during the mean follow-up period of 35.9 ± 30.7 months; the incidence of death was significantly higher in group C than in the other groups (one patient in group A and seven patients in group C). AugPr in RV pressure waveform has prognostic value in patients with PH. Therefore, additional attention should be given to the RV pressure waveform in patients with PH undergoing invasive pressure measurements as a part of their work-up.

Aims Native T1 times from T1 mapping cardiac magnetic resonance (CMR) are associated with myocardial fibrosis in aortic stenosis (AS). We investigated whether changing patterns in native T1 predict clinical outcomes after aortic valve replacement (AVR) in severe AS patients. Methods and results Forty-three patients with severe AS (65.9 ± 8.1 years; 24 men) who underwent T1 mapping CMR at baseline and 1 year after AVR were prospectively enrolled. Upper limit of native T1 from healthy volunteers was used to define normal myocardium and diffuse fibrosis (native T1 Conclusion AVR-induced changes in native T1 values are associated with LV systolic functional changes as well as prognosis in severe AS. Post-AVR T1 mapping CMR can be used as an imaging biomarker.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is believed to represent dense replacement fibrosis. It is seen in ≈60% of adult patients with hypertrophic cardiomyopathy (HCM). However, the prevalence of LGE in children and adolescents with HCM is not well established. In addition, longitudinal studies describing the development and evolution of LGE in pediatric HCM are lacking. This study assesses the prevalence, progression, and clinical correlations of LGE in children and adolescents with, or genetically predisposed to, HCM.CMR scans from 195 patients ≤21 years of age were analyzed in an observational, retrospective study, including 155 patients with overt HCM and 40 sarcomere mutation carriers without left ventricular (LV) hypertrophy. The extent of LGE was quantified by measuring regions with signal intensity6 SD above nulled remote myocardium.Patients were 14.3±4.5 years of age at baseline and 68% were male. LGE was present in 70 (46%) patients with overt HCM (median extent, 3.3%; interquartile range, 0.8-7.1%), but absent in mutation carriers without LV hypertrophy. Thirty-one patients had1 CMR (median interval between studies, 2.4 years; interquartile range, 1.5-3.2 years). LGE was detected in 13 patients (42%) at baseline and in 16 patients (52%) at follow-up CMR. The median extent of LGE increased by 2.4 g/y (range, 0-13.2 g/y) from 2.9% (interquartile range, 0.8-3.2%) of LV mass to 4.3% (interquartile range, 2.9-6.8%) ( P=0.02). In addition to LGE, LV mass and left atrial volume, indexed to body surface area, and z score for LV mass, as well, increased significantly from first to most recent CMR.LGE was present in 46% of children and adolescents with overt HCM, in contrast to ≈60% typically reported in adult HCM. In the subset of patients with serial imaging, statistically significant increases in LGE, LV mass, and left atrial size were detected over 2.5 years, indicating disease progression over time. Further prospective studies are required to confirm these findings and to better understand the clinical implications of LGE in pediatric HCM.

Additional file 2: Univariable Cox proportional hazard regression analysis. A table of results of univariable Cox proportional hazard regression analyses for the occurrence of all-cause mortality in total study population.

Figure S1. Schematic diagram showing the selection process of the patient population. Figure S2. Kaplan-Meier estimates of freedom from paravalvular leakage (PVL) stratified by satisfaction of the International Study Group (ISG) criteria. Figure S3. Kaplan-Meier estimates of freedom from paravalvular leakage (PVL) in patients who received postoperative immunosuppressive therapy (IST), stratified by the use of preoperative (preop) IST. (DOCX 378 kb)

Purpose Udenafil is an oral phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. In a multicenter, placebo-controlled, randomized Phase IIa study, the reduction of pulmonary vascular resistance index was greater with a 50-mg baseline dose of udenafil than with the 100-mg dose, the cardiac index did not decrease at most points, and the safety was excellent, suggesting that 50-mg udenafil could be used in a Phase IIb trial. Methods In this 16-week, double-blind, placebo-controlled study, 63 patients with pulmonary arterial hypertension were randomized to receive 50-mg udenafil or a placebo BID. The primary efficacy end point was the 6-min walking distance. The secondary efficacy end points were the Borg dyspnea score and time to clinical worsening. Patients who completed the 16-week study could participate in a long-term extension study. Findings : In terms of the difference between the baseline and 16-week 6-min walking distance in both groups, the mean placebo-corrected treatment effect was 25 (58) m (P = 0.0873). Among the patients with a history of endothelin receptor antagonist therapy, the treatment effect at week 16 between the udenafil and placebo groups was 34 (60) m (P = 0.0460). However, there were no significant differences in the Borg dyspnea score and time to clinical worsening between groups. The safety profile and adverse effects of udenafil were similar to those of typical phosphodiesterase-5 inhibitors seen in previous studies. Implications Udenafil has a favorable safety profile and improves exercise capacity in patients with pulmonary arterial hypertension. ClinicalTrials.gov identifier: NCT01553721.

Myogenesis occurs in both the prenatal and postnatal periods and the prenatal myogenesis is related to the postnatal myogenesis and the incidence of disease later in life. Glucocorticoids used as therapeutic agents for many diseases, but cause adverse effects on muscle homeostasis, including defects in fetal muscle development. The action of glucocorticoids on differentiated skeletal muscle was well studied, but their effects on myotube formation have not been well investigated. Dexamethasone (DEX) and cortisone (COR), two synthetic therapeutic glucocorticoids, suppress myotube formation in C2C12 cells. Both COR and DEX attenuated myotube formation through modulation of myogenic regulatory factors. In addition, they affected the IGF/PI3K/AKT/mTOR signaling pathway, resulting in increased proteolytic protein (atrogin-1 and MURF1) for muscle degradation and decreased ribosomal S6 phosphorylation. The current results conclude that COR and DEX inhibit myotube formation in C2C12 cells by modulating both the myogenic program via MRFs and protein metabolism via IGF/PI3K/AKT/mTOR signaling pathway. Glucocorticoids decrease myogenesis via AKT/mTOR signal pathway.

Optimal surgical timing is of crucial importance for the treatment of valvular heart diseases. Clinical implications of functional tricuspid regurgitation (TR) are increasingly being recognized. In contrast to the well-established treatment strategies for left-sided valve disease, optimal surgical timing of functional TR has not yet been established. Several lines of evidence have accumulated over the past 10 years, and now is the perfect time to review the data. The present article reviews the clinical implications and treatment strategies of functional TR, particularly in relation to optimal surgical timing. (Korean J Med 2016;91:139-149)

BACKGROUND There is a concern that clinical outcome of tricuspid valve replacement (TVR) is inferior compared with tricuspid annuloplasty (TAP). The aim of this study was therefore to compare changes in right ventricular (RV) volume and function following TAP with that following TVR on cardiac magnetic resonance imaging (CMR) in patients with severe functional tricuspid regurgitation (TR). METHODS AND RESULTS Forty patients who underwent surgery for severe functional TR and who underwent CMR preoperatively and on postoperative follow-up (24.8±13.3 months after surgery) were enrolled. Thirteen patients underwent TAP (TAP group) and 27 patients underwent TVR (TVR group). Both RV end-diastolic and end-systolic volume indices decreased significantly after surgery (from 178.9±53.9 to 116.3±26.7 ml/m(2), P

Subvalvular pannus formation is a rare but clinically important complication that can be missed in patients with prosthetic valves [(1)][1]. The only definite treatment for patients with prosthetic valve obstruction as a result of pannus ingrowth is reoperation. However, currently available

Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham-operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats.

BACKGROUND: The clinical implications of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients are incompletely characterized. We investigated the impact of AF on stroke and mortality, assessed the performance of the CHA2DS2-VASc score, and explored the predictors of stroke in HCM patients. METHODS: A nationwide cohort of HCM patients (n=8,349, mean age 60.7) identified from 2010 to 2015 from the Korean National Health Insurance database were followed up for occurrence of ischemic stroke or all-cause death. RESULTS: During a mean follow-up of 2.5 years, the incidence rate of stroke was 2.69 and 5.87, and mortality rate was 2.06 and 4.44 per 100 person-years in non-AF and AF patients, respectively. AF was independently associated with a 60% and 50% increased risk for stroke and all-cause mortality, respectively. The AF-associated increase in risk of stroke was more prominent in HCM patients with no or few risk factors. The CHA2DS2-VASc score showed poor discrimination of stroke risk in HCM patients with AF, mostly due to the high incidence of stroke in patients with scores of 0 or 1. Traditional risk factors were not always associated with stroke in HCM patients with AF; age, heart failure, high blood pressure and GGT were the strongest predictors of stroke in this population. HCM patients without AF also showed increased incidence of stroke at CHA2DS2-VASc ≥1. CONCLUSIONS: AF was independently associated with increased risks for stroke and all-cause mortality in patients with HCM. The CHA2DS2-VASc score showed poor discrimination of stroke risk in HCM patients with AF.

BackgroundPulmonary arterial hypertension (PAH) is a progressive chronic disease with poor outcomes. One reason for poor prognosis is the lack of understanding regarding individual variability in response to treatment. Idiopathic PAH (IPAH) patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations have distinct phenotypes that are crucial for individualized therapy but evidence regarding their prevalence and clinical features in the Korean population is lacking. Therefore, the present study aimed to screen Korean IPAH patients for BMPR2 mutations and analyze their clinical phenotypes.MethodsWe enrolled 73 unrelated IPAH patients for BMPR2 mutation screening between March 2010 to November 2015 from 11 hospitals in Korea. Thirty-three lineal family members from 6 families of BMPR2 mutation carriers were also screened.ResultsAmong 73 patients, 16 (22%) had BMPR2 mutations. Mutation carriers were younger (27 vs. 47 years; p = 0.02) and had a higher mean pulmonary arterial pressure (mPAP) than non-carriers (64 vs. 51 mmHg; pConclusionThe prevalence of BMPR2 mutations in Korean IPAH patients was 22%. Mutation carriers were younger and had a poorer hemodynamic profile compared with the non-carriers.Clinical trial registrationClinicaltrials.gov NCT01054105.

Cardiac amyloidosis is a rare disease that frequently presents as ventricular hypertrophy. However, diagnosis is not always easy or straightforward as there are several myocardial disorders that phenocopy cardiac amyloidosis. Here, we present a narrative review of the current modalities that are actively used or being developed for diagnosis and follow-up of cardiac amyloidosis. Although not all of the findings may be present in those with cardiac amyloidosis, there are some clues in each diagnostic step that help lead to confirmatory diagnosis of cardiac amyloidosis; we believe that cardiologists should be familiar with these clues.

PURPOSE Recently, the diastolic strain rate (DSR) utilizing speckle-tracking echocardiography has been proposed as a novel parameter for left ventricular diastolic function. We aimed to present normal reference data for those in a large-sized, selected group of healthy individuals. METHODS The current study was a part of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL), a prospective nationwide survey from 23 centers in Korea. We analyzed 447 subjects (age 48 ± 15 years, 234 females) without any history of cardiovascular disease and presented the early and late DSRs (SRe and SRa , respectively) in a total and gender-/age-specified groups. RESULTS Among the total subjects, the mean SRe and SRa were 1.6 ± 0.4 S-1 and 0.8 ± 0.3 S-1 , respectively. With increasing age, there were significant trends of decreasing SRe and increasing SRa . Although both gender groups showed comparable age, the female group presented significantly higher SRe compared to male subjects with age of 20-59 years, which diminished after the age of 60 years. However, the SRa was comparable between genders in all age groups. On multiple linear regression, age showed independent associations with both SRe (β = -0.132, P = .010) and SRa (β = 0.440, P

Aim: Speckle-tracking imaging has been introduced for the precise assessment of vessel mechanics. However, there are no data on the role of this imaging tool in assessing the changes in vasculature with statin therapy, which is known to enhance vascular elasticity. Methods: This study was a prospective study including 48 statin-naive patients (age, 58.2 ± 8.4 years; 29.2% male) with hypercholesterolemia. Circumferential carotid artery strain (CAS) and stiffness index (β2) were measured using speckle-tracking imaging before and after 3 months of high-dose pitavastatin treatment (4 mg daily). For the comparison, we measured conventional carotid elasticity parameters and intima–media thickness using B-mode ultrasound at the same time points. Results: Compared with baseline, there was significant improvement in circumferential CAS (2.98% ± 1.18% to 3.40% ± 1.43%, p = 0.008) and β2 (0.19 ± 0.07 to 0.17 ± 0.08, p = 0.047) after statin therapy. Contrariwise, there were no significant changes in all conventional carotid elasticity metrics and intima–media thickness. When stratifying patients into two subgroups by 10 year atherosclerotic cardiovascular disease (ASCVD) risk, speckle-tracking-derived circumferential CAS and β2 improved significantly only in patients with ASCVD risk ≥ 7.5%. Conclusions: Short-term treatment with high-dose pitavastatin improved carotid artery elasticity measured by speckle-tracking method, but not conventional parameters by B-mode ultrasound. Speckle-tracking-based measurements may allow the early noninvasive assessment of statin effects on vascular function in hypercholesterolemic patients. Abbreviations: CAS: carotid artery strain, β1: classic stiffness index, β2: speckle-tracking-derived stiffness index, IMT: intima-media thickness, ASCVD: atherosclerotic cardiovascular disease, CHD: coronary heart disease, LCL-C: low-density lipoprotein cholesterol, HDL-C: high-density lipoprotein cholesterol, CCA: common carotid artery

The present study evaluated change in left ventricle (LV) biomechanics, layer-by-layer, following acute pressure unloading in patients with severe aortic stenosis (AS). In twenty-eight consecutive patients with severe AS who underwent transcatheter aortic valve replacement (TAVR), LV peak global longitudinal and circumferential strains of the endo-, midmyo- and epicardium were evaluated using multilayer speckle tracking echocardiography before, 1 week after, and 1 month after TAVR. Longitudinal and circumferential strains were significantly highest in the endocardium and lowest in the epicardium at baseline. At 1 month following TAVR, longitudinal strain significantly improved in all layers compared with the baseline [endocardium (%) -16.7 ± 3.8 vs. -18.6 ± 3.3, P = 0.01; mid-myocardium -14.4 ± 3.2 vs. -16.2 ± 3.5, P < 0.01; epicardium -12.4 ± 2.8 vs. -13.6 ± 2.6, P = 0.01], whereas LV ejection fraction and circumferential strain remained unchanged. Importantly, only those with LV hypertrophy demonstrated improved longitudinal strain [endocardium (%) -15.7 ± 3.0 vs. -18.7 ± 2.9, P < 0.01; mid-myocardium -13.6 ± 2.7 vs. -16.0 ± 2.5, P < 0.01; epicardium -11.8 ± 2.4 vs. -13.7 ± 2.3, P < 0.01]. The improvement in longitudinal strain was more prominent in the endocardium, which was evident even at an early time point (1 week) after TAVR. Longitudinal strain significantly improved in all three layers following acute pressure unloading, the most prominent of which was observed in the endocardium. Evaluation of multilayer strain may provide new insights into the LV mechanics in the future.

System is the organization of hardware, software, personnel a nd facilities needed to perform a designated function within a stated environment with specified results. The trend of modern systems is getting more complex and larger. The system is necessary for mo dern society but the minor malfunction of the system can result the enormous human and mat erial losses. Recently it is being heightened the concern for system safety and required to be bui lt and applied Safety Engineering standard Guideline for safety of complex and large-sized system . This paper describes the System Engineering Process model integrated with Safety Engineering an d the establishment of standard safety guidelines for safety of product development using DMADOV Metho dology of the Lean 6 Sigma. Keywords : Safety Engineering, Safety Process, Safety Standard Guideline, Lean 6 Sigma, DMADOV 1. 서 론 안전(Safety)이란 사망, 부상, 직업병, 손상을 유발하거나 장비 및 재산에 대한 손실 또는 환경피해를 일으킬 수 있는 우려가 없는 상태 또는 조건을 의미한다. 현대 안전공학 사고이론 중 하나인 ‘도미노’ 이론의 창시자인 하인리히(H. W. Heinrich)는 “사고나 재난은 발생 전에 여러 가지 징후가 나타나므로 이에 대한 분석과 준비를 통해 미리 예방할 수 있다”고 주장하였고, 밥 휘렌츠(Bob Firenze)는 사고를 사람, 기계 및 환경이란 시스템 속에서 일어난 현상으로 보았으며 인간이 기계와 환경에 조화되어야 효율적이라고 보았다. 즉, 기계의 설계가 불량하거나 불안전할 때 사고의 원인이 될 수 있고 환경은 인간과 기계에 영향을 주어 사고를 조장하거나 유발한다고 보았다[1][2]. 특히 특정 기능을 수행하기 위한 복합체인 시스템에 있어서는 이러한 안전성의 확보는 매우 중요한 문제이다. 현대의 시스템은 사회의 다양한 분야에서 사용되고 있으며 전자 및 정보기술 분야의 비약적인 발전으로 인하여 기존의 아날로그 시스템에 비하여 하드웨어뿐 아니라 소프트웨어적으로도 더욱 복잡한 제어 기능을 수행하고 대형 시스템화가 되어가는 추세이다. 시스템이 복잡화 및 대형화됨에 따라 고장의 예측이 어려워졌으며, 사소한 고장이나 오작동이 대형 사고를 유발할 수 있다는 점에서 시스템의 신뢰성 및 안전성확보 문제가 대두되고 있다. 국가기반시스템, 산업제어시스템, 군사무기체계 등은 고장이 발생할 경우 사회 ․ 경제적으로 큰 문제를 야기할 수 있는 안전성이 매우 중요한†Corresponding Author : Hyung-Kwan Kim, Naval/System RD Revision Received May 07, 2015; Accepted June 14, 2015.

Backgrounds Paroxysmal atrial fibrillation (AF) frequently, but not always, progresses to persistent/permanent AF. The aim of this study was to evaluate the echocardiographic predictors of AF progression in patients with paroxysmal AF. Methods A multicenter, prospective, observational study was conducted that included 313 patients with paroxysmal AF who underwent two-dimensional speckle-tracking echocardiography. The diameter, volume, and mechanical function of the left atrium, including global strain (e) and e rate, were measured. Results Progression to persistent or permanent AF occurred in 52 patients (16.6%) during a median follow-up period of 26 months. Echocardiographic measure of left atrial (LA) diameter, volume, and function (E velocity, E/A and E/e′ ratio, LA expansion index, active emptying fraction, global longitudinal e and e rate) were associated with AF progression. LA e ≤ 30.9% was the strongest predictor of AF progression, which was associated with a more than fourfold hazard increase for AF progression (hazard ratio, 4.224; P = .001). LA diameter > 39 mm and maximal LA volume index > 34.2 mL/m 2 were associated with about a twofold hazard increase for AF progression (hazard ratios, 1.994 and 2.649; P = .016 and P = .001, respectively). When adjusted for a model combining maximal LA volume index, E velocity, LA expansion index, and active emptying fraction, LA e ≤ 30.9% maintained a more than threefold hazard increase for AF progression (adjusted hazard ratio, 3.970; P = .003). Conclusions Echocardiographic measures of LA diameter, volume, and mechanical function, including LA e, were associated with AF progression. LA e was the strongest independent predictor of AF progression and is expected to serve as a valuable predictor of AF progression.

This study was performed to determine whether the newly developed phosphodiesterase type 5 (PDE5) inhibitor udenafil had beneficial effects on pressure-overload cardiac hypertrophy. Pressure overload cardiac hypertrophy was created by using suprarenal aortic constriction (SAC) in male Sprague-Dawley rats. Rats were divided into three groups: sham (n=19), SAC (n=18) and SAC+udenafil (n=14) groups. Three-week periods of SAC provoked significant left ventricular (LV) hypertrophy. Udenafil was administered (20 mg kg(-1) PO, daily) between the 3rd and 20th weeks after SAC in the SAC+udenafil group. Udenafil improved the survival rate (log-rank P=0.012) and exercise capacity (maximal exercise duration at the 20th week after surgery: 448±54 s for the SAC+udenafil group versus 317±73 s for the SAC group, P0.05) of the rats with SAC. Serial echocardiographic examinations showed that udenafil attenuated LV remodeling processes following SAC (mean LV end-diastolic dimension at the 20th week after surgery: 9.84±0.59 mm for SAC and 9.05±0.58 mm for SAC+udenafil group, P0.05). Invasive hemodynamic studies showed that udenafil improved the LV performance. Udenafil-attenuated myocardial fibrosis and apoptosis. Udenafil also decreased myocardial matrix metalloproteinase-9 expression and augmented serum interleukin-10 concentration. Long-term udenafil use prevented cardiac remodeling and improved exercise capacity and survival in rats exposed to pressure-overload cardiac hypertrophy.

Non-obstructive coronary artery disease (CAD) is a frequent clinical condition and is associated with an increase in cardiovascular events. However, appropriate medical therapy for this population is not known. We investigated the association between statin use and risk of all-cause mortality and coronary revascularization in patients with non-obstructive CAD.From 2007 to 2011, we identified 8372 consecutive patients with non-obstructive CAD (1-49% stenosis) documented by coronary computed tomography angiography (CCTA) from 3 medical centers. Patients with statins or aspirin use before CCTA, and a history of revascularization before initial CCTA were excluded. All-cause mortality and a composite of mortality and late coronary revascularization (90 days after CCTA) were analyzed according to the use of statins.Mean age of the study population was 61.4 ± 10.9 years and 70.3% were male. Statins were prescribed to 1983 (23.7%) patients. During 828 days of follow-up (IQR 385-1342), 221 (2.6%) cases of all-cause mortality and 295 (3.5%) cases of the composite endpoint were observed. Statin therapy was associated with lower risks of all-cause mortality (adjusted HR 0.397; 95% CI 0.262-0.602; p0.0001) and composite endpoint (adjusted HR 0.430; 95% CI 0.310-0.597; p0.0001). Association between statin therapy and better clinical outcomes was regardless of age, sex, presence of hypertension or diabetes, coronary artery calcium score, low-density lipoprotein cholesterol levels, high-sensitivity C-reactive protein levels, or glomerular filtration rate.Statin therapy was associated with a lower risk of all-cause mortality in patients with non-obstructive CAD documented by CCTA, regardless of combined clinical risk factors.

Background LV pressure overload triggers biological events leading to LV hypertrophy, and the severity of LV pressure overload has been represented by LV wall stress (LVWS). However, duration of exposure to the given LVWS has not been considered as a factor leading to LV hypertrophy. Methods In 20 patients with severe aortic stenosis, LV pressure, with a Millar catheter, and LV dimensions, with echocardiography, were simultaneously obtained. By synchronising LV pressure waveform and LV dimensions, the instantaneous peak LVWS (IP-LVWS) and systolic LV wall time-stress-integral (LV TSI), which is the LVWS integrated during the systolic period and physically implies LV wall impulse per unit area, were obtained. These measurements were obtained at rest, during right atrial pacing at an HR of 10% higher than resting HR, and after esmolol infusion. Results IP-LVWS cannot be predicted from the peak LV pressure or peak dp/dt. There were no significant differences in peak IP-LVWS at rest, during pacing or after esmolol infusion. However, systolic LV TSI after esmolol infusion was significantly higher compared to that at rest or during pacing. Only LV TSI correlated with LV wall thickness or LV mass at rest (r=0.64, p=0.002 and r=0.54, p=0.014, respectively), while correlations between IP-LVWS and LV wall thickness or LV mass at rest were not statistically significant (r=0.32, p=0.173 and r=0.32, p=0.168, respectively). Conclusions As IP-LVWS cannot be predicted from the peak LV pressure or peak dp/dt, one should be cautious in interpreting the data regarding peak LV pressure as the parameter representing LV afterload. Based on the current results, the systolic LV TSI might be more important than IP-LVWS in LV hypertrophy. In addition, as LV TSI is affected by the systolic duration, factors prolonging systolic duration might exert adverse effects on LV hypertrophy.

To assess whether native T1 mapping provides noninvasive estimation of diffuse myocardial fibrosis and whether it correlates with subclinical myocardial dysfunction in asymptomatic patients with aortic stenosis (AS).The local institutional review board approved the study, and all patients gave informed consent. Eighty asymptomatic patients with moderate or severe AS and normal left ventricular (LV) ejection fraction (mean age, 67 years; range, 31-81 years) and 15 sex-matched control subjects (mean age, 33 years; range, 23-41 years) were prospectively enrolled. Patients underwent two-dimensional echocardiography, speckle tracking imaging, and cardiac 3.0-T magnetic resonance (MR) imaging, including mapping of T1 relaxation time by using the modified Look-Locker inversion-recovery sequence. Correlations between native T1 values and the degree of diffuse fibrosis in myocardial specimens obtained during aortic valve replacement surgery were analyzed in a subset of 20 patients. Correlations between parameters of myocardial function and structure and native T1 values were assessed with Pearson correlation coefficients.Native T1 values correlated well with the degree of diffuse myocardial fibrosis in intraoperative myocardial biopsy specimens (r = 0.777, P.001) and differed significantly between patients with AS and control subjects (1208 msec ± 45 vs 1169 msec ± 21, P.001). LV volumes and mass differed significantly according to AS groups, categorized by T1 tertiles (all P.001), as well as degree of AS severity (0.55 cm(2)/m(2) ± 0.14 for lowest native T1 tertile, 0.46 cm(2)/m(2) ± 0.12 for middle native T1 tertile, and 0.45 cm(2)/m(2) ± 0.13 for highest native T1 tertile [P = .008] for indexed aortic valve area at echocardiography). Native T1 correlated significantly with global longitudinal strain measured with two-dimensional speckle tracking imaging (r = 0.598, P.001), e' velocity (r = -0.437, P.001), and indexed left atrial volume (r = 0.475, P.001).Native T1 mapping provides a noninvasive estimation of diffuse myocardial fibrosis and correlates with subclinical myocardial dysfunction in asymptomatic patients with AS.

BACKGROUND Relative apical sparing pattern of longitudinal strain (RapSP-LS) was suggested in advanced cardiac amyloidosis (CA). It is unclear whether it is present in less advanced CA. METHODS AND RESULTS Patients with presumptive diagnosis of CA and mean left ventricular wall thickness (LVWT) ≤14 mm were recruited. Apart from RapSP-LS visually identified, relative apical longitudinal strain index (RapLSI) was defined as [average apical LS/(average basal LS+average mid-ventricle LS)]. Among 119 patients included, 47 were finally diagnosed with CA. RapLSI was higher in the CA group compared to other causes of increased mean LVWT (P

Objective To evaluate the influence of papillary muscles and trabeculae on left ventricular (LV) cardiovascular magnetic resonance (CMR) analysis using three methods of cavity delineation (classic or modified inclusion methods, and the exclusion method) in patients with hypertrophic cardiomyopathy (HCM). Materials and Methods This retrospective study included 20 consecutive HCM patients who underwent 1.5-T CMR imaging with short-axis cine stacks of the entire LV. LV measurements were performed using three different methods of manual cavity delineation of the endocardial and epicardial contours: method A, presumed endocardial boundary as seen on short-axis cine images; method B, including solely the cavity and closely adjacent trabeculae; or method C, excluding papillary muscles and trabeculae. Ascending aorta forward flow was measured as reference for LV-stroke volume (SV). Interobserver reproducibility was assessed using intraclass correlation coefficients. Results Method A showed larger end-diastole and end-systole volumes (largest percentage differences of 25% and 68%, respectively, p < 0.05), compared with method C. The ejection fraction was 55.7 ± 6.9% for method A, 68.6 ± 8.4% for B, and 71.7 ± 7.0% for C (p < 0.001). Mean mass was also significantly different: 164.6 ± 47.4 g for A, 176.5 ± 50.5 g for B, and 199.6 ± 53.2 g for C (p < 0.001). LV-SV error was largest with method B (p < 0.001). No difference in interobserver agreement was observed (p > 0.05). Conclusion In HCM patients, LV measurements are strikingly different dependent on whether papillary muscles and trabeculae are included or excluded. Therefore, a consistent method of LV cavity delineation may be crucial during longitudinal follow-up to avoid misinterpretation and erroneous clinical decision-making.

Background Carotid intima-media thickness (CIMT) is associated with an increased risk of cardiovascular disease. We studied whether CIMT predicts the prognosis of Asian patients with acute ST-elevation myocardial infarction (STEMI). Methods A total of 345 patients with STEMI (men, 82.9%; age, 59 ± 13 years) treated with emergent revascularization were prospectively investigated. In all patients, common CIMT was measured with high-resolution ultrasonography. The patients were followed for a median period of 583 days, and the primary end point was major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, heart failure, nonfatal recurrent MI, revascularization, and stroke. Results Mean CIMT of the patients with STEMI was 0.77 ± 0.14 mm. Of the total patients, 20.6% had carotid plaque and 11.0% experienced MACE. Killip class, left ventricular (LV) function, and carotid plaque were associated with 30-day MACE, whereas CIMT and carotid plaque were related to overall MACE. After adjusting for age, the event rate was 19.0% in the third-tertile CIMT (≥ 0.83 mm) group, 12.1% in the second-tertile (0.70-0.82 mm) group, and 4.3% in the first-tertile (≤ 0.69 mm) group ( P = 0.01). Carotid plaque was independently associated with a higher incidence of MACE (adjusted odds ratio [OR], 3.7; 95% confidence interval [CI], 1.327-10.234; P = 0.012). Area under the receiver operating characteristic (ROC) curve for CIMT tertile (0.69 ± 0.05) was significantly larger compared with those for door-to-balloon time (0.55 ± 0.05), LV ejection fraction (LVEF) (0.49 ± 0.05), and Killip class (0.48 ± 0.05) ( P Conclusions CIMT was a useful prognosticator to predict future cardiovascular events (CVEs) in Asian patients with STEMI.

Background The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS). Methods/design The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease. Discussion In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy. Trial registration ClinicalTrials.gov, NCT02940366. Registered on 19 October 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2229-4) contains supplementary material, which is available to authorized users.