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Hyperuricemia is related to an increased risk of cardiovascular events from a meta-analysis and antihyperuricemia agents may influence to cardiac function. We evaluated the effect of febuxostat on echocardiographic parameters of diastolic function in patients with asymptomatic hyperuricemia as a prespecified endpoint in the subanalysis of the PRIZE study. Patients in the PRIZE study were assigned randomly to either add-on febuxostat treatment group or control group with only appropriate lifestyle modification. Of the 514 patients in the overall study, 65 patients (31 in the febuxostat group and 34 in the control group) who had complete follow-up echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included. The primary endpoint was a comparison of the changes in the E/e′ between the two groups from baseline to 24 months. Interestingly, e′ was slightly decreased in the control group compared with in the febuxostat group (treatment p = 0.068, time, p = 0.337, treatment × Time, p = 0.217). As a result, there were significant increases in E/e′ (treatment p = 0.045, time, p = 0.177, treatment × time, p = 0.137) after 24 months in the control group compared with the febuxostat group. There was no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive troponin I between the two groups during the study period. In conclusions, additional febuxostat treatment in patients with asymptomatic hyperuricemia for 24 months might have a potential of preventable effects on the impaired diastolic dysfunction.

Infective endocarditis (IE) may be acquired in the community as community-acquired (CA) IE or in the healthcare setting. In Japan, cases of CA-methicillin-resistant Staphylococcus aureus (MRSA) infection as skin infection have been increasing. CA-MRSA strains, including the USA300 clone, have higher pathogenicity and are more destructive to tissue than healthcare-associated MRSA strains because of the toxins they produce, including arginine-catabolic mobile element (ACME) and Panton-Valentine leukocidin (PVL). However, only a few IE cases induced by USA300 have been reported. We herein report a 64-year-old man who developed CA-IE from a furuncle caused by USA300 MRSA producing PVL and ACME, which resulted in complications of meningitis.

Background Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. Methods Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. Results The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89–1.08) in the canagliflozin group and 1.07 (95% CI 0.97–1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82–1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e′) showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e′ Conclusions In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

Background To accurately diagnose and control heart failure (HF), it is important to carry out a simple assessment of elevated pulmonary arterial wedge pressure (PAWP). The aim of this study was to develop and validate an objective method for detecting elevated PAWP by applying deep learning (DL) to a chest x-ray (CXR). Methods We enrolled 1013 consecutive patients with a right-heart catheter between October 2009 and February 2020. We developed a convolutional neural network to identify patients with elevated PAWP (> 18 mm Hg) as the actual value of PAWP to be used in the dataset for training. In the prospective validation dataset used to detect elevated PAWP, the area under the receiver operating characteristic curve (AUC) was calculated using the DL model that evaluated the CXR. Results In the prospective validation dataset, the AUC of the DL model with CXR was not significantly different from the AUC produced by brain natriuretic peptide (BNP) and the echocardiographic left-ventricular diastolic dysfunction (DD) algorithm (DL model: 0.77 vs BNP: 0.77 vs DD algorithm: 0.70; respectively; P = NS for all comparisons); it was, however, significantly higher than the AUC of the cardiothoracic ratio (DL model vs cardiothoracic ratio [CTR]: 0.66, P = 0.044). The model based on 3 parameters (BNP, DD algorithm, and CTR) was improved by adding the DL model (AUC: from 0.80 to 0.86; P = 0.041). Conclusions Applying the DL model based on a CXR (a classical, universal, and low-cost test) is useful for screening for elevated PAWP.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 +/- 2 to 9 +/- 3, from 10 +/- 2 to 12 +/- 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 +/- 5 to 17 +/- 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 +/- 13 to 44 +/- 14 mL/m(2), P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Background Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF.Methods and Results:In Study 1, PAR2 deficient (PAR2-/-) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8 h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2-/- mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes. Conclusions The FXa-PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation.

Despite recent advances in imaging for myocardial deformation, left ventricular ejection fraction (LVEF) is still the most important index for systolic function in daily practice. Its role in multiple fields (e.g., valvular heart disease, myocardial infarction, cancer therapy-related cardiac dysfunction) has been a mainstay in guidelines. In addition, assessment of LVEF is vital to clinical decision-making in patients with heart failure. However, notable limitations to LVEF include poor inter-observer reproducibility dependent on observer skill, poor acoustic windows, and variations in measurement techniques. To solve these problems, methods for standardization of LVEF by sharing reference images among observers and artificial intelligence for accurate measurements have been developed. In this review, we focus on the standardization of LVEF using reference images and automated LVEF using artificial intelligence.

Background Radiofrequency (RF) ablation of typical atrioventricular nodal reentrant tachycardia (tAVNRT) is performed without revealing out the location of antegrade slow pathway (ASp). In this study, we studied a new electrophysiological method of identifying the site of ASp. Methods This study included 19 patients. Repeated series of very high‐output single extrastimulations (VhoSESts) were delivered at the anatomical slow pathway region during tAVNRT. Tachycardia cycle length (TCL), coupling interval (CI), and return cycle (RC) were measured and the prematurity of VhoSESts [ΔPM (= TCL – CI)] and the prolongation of RCs [ΔPL (= RC – TCL)] were calculated. Pacing sites were classified into two categories: (i) ASp capture sites [DSPC(+) sites], where two different RCs were shown, and ASp non‐capture sites [DSPC(‐) sites], where only one RC was shown. RF ablation was performed at DSPC(+) sites and/or sites with catheter‐induced mechanical trauma (CIMT) to ASp. Results DSPC(+) sites were shown in 13 patients (68%). RF ablation was successful in all patients without any degree of atrioventricular block nor recurrence. Total number of RF applications was 1.8 ± 1.1. Minimal distance between successful ablation sites and DSPC(+)/CIMT sites and His bundle (HB) electrogram recording sites was 1.9 ± 0.8 mm and 19.8 ± 6.1 mm, respectively. ΔPL of more than 92.5 ms, ΔPL/TCL of more than 0.286, and ΔPL/ΔPM of more than 1.565 could identify ASp with sensitivity of 100%, 91.1%, and 88.9% and specificity of 92.9%, 97.0%, and 97.6%, respectively. Conclusions Sites with ASp capture and CIMT were close to successful ablation sites and could be useful indicators of tAVNRT ablation., A case of Direct Slow Pathway Capture (DSPC) during typical atrioventricular nodal reentrant tachycardia.

Objectives. Cilnidipine, an L-/N-type calcium channel blocker (CCB), has unique organ-protective properties due to suppression of hyperactivity in the sympathetic nervous system and renin-angiotensin system (RAS). In this study, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing the RAS. Methods. A total of 25 hypertensive patients receiving a RAS inhibitor were randomly assigned to a cilnidipine (n = 12) or amlodipine (n = 13) group. The effects of cilnidipine on proteinuria and angiotensin II–renin feedback were assessed. Results. After 6 months of treatment, both systolic and diastolic blood pressures were significantly reduced to a similar extent in both groups. The urine albumin-to-creatinine ratio was significantly lower in the cilnidipine group ( p < 0.05 ) than in the amlodipine group. Amlodipine increased plasma angiotensin I and angiotensin II levels ( p < 0.05 ), whereas cilnidipine did not. Interestingly, the cilnidipine group had a higher ratio of angiotensin-(1–7) (Ang-(1–7)) to angiotensin II in plasma than the amlodipine group ( p < 0.05 ). Conclusions. The L-/N-type CCB cilnidipine, but not amlodipine, decreased urinary albumin excretion in hypertensive patients. Cilnidipine also increased the ratio of Ang-(1–7) to angiotensin II in plasma, which might be one factor underlying its beneficial effects.

Accurate diagnosis of pulmonary hypertension (PH) is crucial to ensure that patients receive timely treatment. We hypothesized that application of artificial intelligence (AI) to the chest X-ray (CXR) could identify elevated pulmonary artery pressure (PAP) and stratify the risk of heart failure hospitalization with PH. We retrospectively enrolled a total of 900 consecutive patients with suspected PH. We trained a convolutional neural network to identify patients with elevated PAP (> 20 mmHg) as the actual value of PAP. The endpoints in this study were admission or occurrence of heart failure with elevated PAP. In an independent evaluation set for detection of elevated PAP, the area under curve (AUC) by the AI algorithm was significantly higher than the AUC by measurements of CXR images and human observers (0.71 vs. 0.60 and vs. 0.63, all p

Artificial intelligence (AI) has influenced every field of cardiovascular imaging in all phases from acquisition to reporting. Compared with computed tomography and magnetic resonance imaging, there is an issue of high observer variation in the interpretation of echocardiograms. Therefore, AI can help minimize the observer variation and provide accurate diagnosis in the field of echocardiography. In this review, we summarize the necessity for automated diagnosis in the echocardiographic field, and discuss the results of AI application to echocardiography and future perspectives. Currently, there are two roles for AI in cardiovascular imaging. One is the automation of tasks performed by humans, such as image segmentation, measurement of cardiac structural and functional parameters. The other is the discovery of clinically important insights. Most reported applications were focused on the automation of tasks. Moreover, algorithms that can obtain cardiac measurements are also being reported. In the next stage, AI can be expected to expand and enrich existing knowledge. With the continual evolution of technology, cardiologists should become well versed in this new knowledge of AI and be able to harness it as a tool. AI can be incorporated into everyday clinical practice and become a valuable aid for many healthcare professionals dealing with cardiovascular diseases. Electronic supplementary material The online version of this article (10.1007/s12574-020-00496-4) contains supplementary material, which is available to authorized users.

This study sought to evaluate the role of cardiac magnetic resonance (CMR) for the quantification of ischemic mitral regurgitation (IMR) and myocardial infarct size (MIS) in patients with ischemic cardiomyopathy (ICM). This study also sought to explore the interaction between IMR severity and MIS and its association with outcomes in patients with ICM.IMR occurs secondary to a disease of the left ventricle and is associated with poor outcomes. The role of CMR for the evaluation and risk stratification of patients with ICM and IMR remains uncertain.Consecutive patients with ICM who underwent baseline CMR were included. MIS was quantified on late gadolinium enhancement imaging as the proportion of left ventricular mass. IMR was quantified with CMR by calculating the mitral regurgitant fraction (MRFraction). Cox proportional hazards models were built to assess the association of IMR and MIS quantification with the combined endpoint of all-cause death or heart transplant.We evaluated 578 patients (mean age: 62 ± 11 years, 76% males). The mean left ventricular ejection fraction was 25 ± 11%, with an MIS of 24 ± 16% and MRFraction of 18 ± 17%. Over a median follow-up time of 4.9 years, 198 (34%) patients experienced death or cardiac transplant. On multivariable analysis, after comprehensive medical risk score, subsequent revascularization, implantable cardioverter-defibrillator insertion, and surgical mitral valve intervention were controlled for, the interaction of IMR severity and MIS emerged as a powerful predictor of adverse outcomes (p = 0.008). For patients with significant IMR (MRFraction: ≥35%), the hazard ratio comparing moderate MIS (15% to 29%) versus small MIS (15%) was 1.51 (0.57 to 3.98), and the hazard ratio comparing large MIS (≥30%) versus small MIS was 5.41 (2.34 to 12.7).Risk associated with IMR is more comprehensively described as an interaction between IMR severity and MIS. Further studies in patients IMR using comprehensive CMR evaluation are needed to verify whether this approach can improve patient selection and procedural outcomes to address IMR.

Early worsening heart failure (WHF), defined as worsening of symptoms and signs of heart failure requiring intensification of medical or mechanical therapy during an admission for acute decompensated heart failure (ADHF), has recently been recognized as a risk of morbidity or mortality after the discharge. Although echocardiographic parameters of left ventricular (LV) output has been shown to be associated with long-term outcome in heart failure patients, its predictive value for early WHF has not been elucidated. Prospect trial to Elucidate the utility of EchocarDiography-based Cardiac output in acute heart failure (PREDICT) is a multicenter, nonrandomized, prospective observational study to test the predictive value of echocardiographic LV output parameters for early WHF in ADHF patients. We will enroll patients admitted to 16 participating hospitals due to ADHF who did not receive positive inotropic agents as an initial therapy. Primary outcome will be set at early WHF defined as need for initiation of positive inotropic agents within 7 days after the admission. Predictive accuracy will be compared between Doppler echocardiographic LV output (stroke distance, stroke volume index, and cardiac index) and low perfusion findings assessed by physical examination. N/A. The PREDICT is expected to provide large data set to test the predictive value of echocardiographic LV output for early WHF in ADHF patients.

ObjectiveThe aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up.MethodsWe retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up.ResultsLVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, pConclusionsBasal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.

Echocardiography is the most common modality to assess left ventricular (LV) diastolic function. Conventional methods reflecting LV diastolic function are routinely used, including transmitral flow velocities, tissue Doppler velocities, continuous wave Doppler velocities, and left atrial size. These measures have a potential to predict adverse outcomes in several cardiovascular diseases. However, there is no perfect echocardiographic measure to assess diastolic dysfunction. Using a combination of advanced echocardiographic techniques, including strain at the left ventricle, left atrium, and right ventricle, diastolic function can be evaluated among a wide range of cardiovascular diseases.

Background Neointimal maturation after bioresorbable-polymer (BP) drug-eluting stent (DES) implantation will not be complete in the absorption phase of the polymer. We have previously reported local persistent hypercoagulation after sirolimus-eluting stent (SES) implantation by measuring local plasma prothrombin fragment 1+2 (F1+2) levels. The aim of this study is to examine time-dependent local coagulative response after BP-DES implantation. Methods Sixty-four patients who were treated about ten months earlier with coronary angioplasty, with no evidence of restenosis, were studied [durable-polymer (DP)-DES {SES; Cypher®: 26pts and everolimus-eluting stent (EES); Xience®: 16pts} and BP-DES (BP-EES; Synergy®: 10pts and BP-SES; Ultimaster®: 12pts)]. We measured plasma levels of F1+2 sampled in coronary sinus (CS) and sinus of Valsalva (V) at the early (2±1 months) and chronic (10±2 months) phases. The transcardiac gradient (Δ) was defined as CS level minus V level. Results No significant differences were observed in the percent diameter stenosis between the DP- and BP- DES groups (11.5±15.5 vs 14.1±11.9%). The ΔF1+2 was significantly lower in the BP-DES group than in the DP-DES group at the chronic phase (7.5±16.1 vs 16.4±17.1pmol/l, p Conclusion Lower local coagulative response was observed at the chronic phase after BP-DES implantation compared to DP-DES implantation, and local hypercoagulation after BP-DES implantation was not observed at the early phase compared to the chronic phase. These findings might lead to the possibility of shorter dual antiplatelet therapy after BP-DES implantation. Funding Acknowledgement Type of funding sources: None.

BackgroundCardiovascular diseases are the second most common cause of mortality among cancer survivors, after death from cancer. We sought to assess the impact of cancer on the short-term outcomes of acute myocardial infarction (AMI), by analysing data obtained from a large-scale database.MethodsThis study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination. We identified patients who were hospitalised for primary AMI between April 2012 and March 2017. Propensity Score (PS) was estimated with logistic regression model, with cancer as the dependent variable and 21 clinically relevant covariates. The main outcome was in-hospital mortality.ResultsWe split 1 52 208 patients into two groups with or without cancer. Patients with cancer tended to be older (cancer group 73±11 years vs non-cancer group 68±13 years) and had smaller body mass index (cancer group 22.8±3.6 vs non-cancer 23.9±4.3). More patients in the non-cancer group had hypertension or dyslipidaemia than their cancer group counterparts. The non-cancer group also had a higher rate of percutaneous coronary intervention (cancer 92.6% vs non-cancer 95.2%). Patients with cancer had a higher 30-day mortality (cancer 6.0% vs non-cancer 5.3%) and total mortality (cancer 8.1% vs non-cancer 6.1%) rate, but this was statistically insignificant after PS matching.ConclusionCancer did not significantly impact short-term in-hospital mortality rates after hospitalisation for primary AMI.

Background Recent studies have shown that patients with combined pre- and postcapillary pulmonary hypertension (CpcPH) had worse outcomes than those with isolated postcapillary pulmonary hypertension (IpcPH). However, the prognostic factors including right ventricular (RV) function have not been well documented. The aim of this study was to assess the differentiation of PH phenotypes, using echocardiography, and the association between RV longitudinal strain and cardiac events. Methods and Results We prospectively recruited consecutive patients who had undergone right heart catheterization. The primary endpoint was cardiovascular death or readmission due to heart failure. We included 137 patients with Group 2 PH. A RV longitudinal strain of 17% was sensitive (85%) and specific (70%) to determine the CpcPH. During a median period of 31 months, 43 patients experienced the primary endpoint during follow-up. In a multivariate analysis, RV longitudinal strain was associated with the primary endpoint in both CpcPH and IpcPH (HR: 0.84, P = 0.003; HR: 0.86, P = 0.001). Conclusions Lower RV longitudinal strain was independently associated with worse outcomes in CpcPH and IpcPH. RV longitudinal strain may play a prognostic role in PH phenotypes.

Background Cardiac amyloidosis (CA) is a secondary form of cardiomyopathy where abnormal accumulation of amyloid protein in the myocardial interstitium causes cardiac hypertrophy and myocardial fibrosis. If primary CA advances to heart failure, most patients do not survive for very long after the diagnosis. Case summary A 40-year-old man was admitted to our hospital for dyspnoea, progressive anaemia, and decreased appetite. He has diagnosed with amyloid light-chain (AL) amyloidosis. Although BD treatment (bortezomib + dexamethasone) and medical treatment were started, there was no sign of improvement. Then, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) was initiated. Pretreatment echocardiography revealed typical findings of CA, such as ventricular wall thickening, valvular thickening, diastolic dysfunction, and pericardial effusion. Global longitudinal strain (GLS) was significantly reduced, and bull's-eye mapping showed typical apical sparing. After auto-PBSCT, GLS gradually improved and was almost normal after 2 years. Other echocardiographic parameters, functional status, and laboratory data also showed that there was significant regression of CA. Discussion Although the prognosis in primary CA is extremely poor, we achieved long-term survival in a patient with effective high-dose chemotherapy and auto-PBSCT. Global longitudinal strain may be a useful marker of prognosis, regression, and recovery.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel antidiabetic agents with possible vascular protection effects. Endothelial dysfunction is an initiation step in atherogenesis. The purpose of this study was to investigate whether vildagliptin (Vilda) attenuates the development of endothelial dysfunction and atherosclerotic lesions in nondiabetic apolipoprotein E-deficient (ApoE-/-) mice. Eight-week-old nondiabetic ApoE-/- mice fed a Western-type diet received Vilda (50 mg/kg/day) for 20 weeks or 8 weeks. After 20 weeks of treatment, Vilda administration reduced atherogenesis in the aortic arch as determined by en face Sudan IV staining compared with the vehicle group (P < 0.05). Vilda also reduced lipid accumulation (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) expression (P < 0.05) and tended to decrease macrophage infiltration (P = 0.05) into atherosclerotic plaques compared with vehicle. After 8 weeks of treatment, endothelium-dependent vascular reactivity was examined. Vilda administration significantly attenuated the impairment of endothelial function in nondiabetic ApoE-/- mice compared with the vehicle group (P < 0.05). Vilda treatment did not alter metabolic parameters, including blood glucose level, in both study protocols. To investigate the mechanism, aortic segments obtained from wild-type mice were incubated with exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analog, in the presence or absence of lipopolysaccharide (LPS). Ex-4 attenuated the impairment of endothelium-dependent vasodilation induced by LPS (P < 0.01). Furthermore, Ex-4 promoted phosphorylation of eNOS at Ser1177 which was decreased by LPS in human umbilical endothelial cells (P < 0.05). Vilda inhibited the development of endothelial dysfunction and prevented atherogenesis in nondiabetic ApoE-/- mice. Our results suggested that GLP-1-dependent amelioration of endothelial dysfunction is associated with the atheroprotective effects of Vilda.

Background: Whether preoperative echocardiography improves postoperative outcomes is not well established, so we examined the value of echocardiographic assessment on the onset of postoperative heart failure (HF), and determining which patients benefitted most from undergoing echocardiography prior to major elective non-cardiac surgery. Methods and Results: We identified all patients aged 50 years and older who had major elective non-cardiac surgery, and excluded patients with previously identified severe cardiovascular disease. The primary endpoint was the onset of HF during hospitalization. A total of 806 patients were included in the analysis. During hospitalization, 49 patients (6%) reached the primary endpoint. Within the matched cohort, preoperative echocardiography was associated with a statistically significant decrease in postoperative HF (hazard ratio: 0.46, P=0.01). In subgroup analyses, age, sex, body surface area, hypertension, diabetes mellitus, prior HF, surgical type, chronic kidney disease, pulmonary disease, and malignancy influenced the association of echocardiography with postoperative HF. Conclusions: The use of echocardiography in elderly patients with certain risk factors was associated with improved postoperative outcomes. The basis for this finding remains to be determined; particularly whether echocardiography is simply a marker of a population with better outcomes or whether it leads to better management that improves outcomes.

Abnormal pulmonary vascular response to exercise can be a marker of early pulmonary arterial hypertension (PAH). We have previously demonstrated that the pressure-flow relationship of mean pulmonary artery pressure (mPAP) to cardiac output (CO) measurement could be applied to predict future

Aim: It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited. Methods: A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography. Results: The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR. Conclusion: Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.

Genetic testing provides valuable insights into family screening strategies, diagnosis, and prognosis in patients with hypertrophic cardiomyopathy (HCM). On the other hand, genetic testing carries socio-economical and psychological burdens. It is therefore important to identify patients with HCM who are more likely to have positive genotype. However, conventional prediction models based on clinical and echocardiographic parameters offer only modest accuracy and are subject to intra- and inter-observer variability. We therefore hypothesized that deep convolutional neural network (DCNN, a type of deep learning) analysis of echocardiographic images improves the predictive accuracy of positive genotype in patients with HCM. In each case, we obtained parasternal short- and long-axis as well as apical 2-, 3-, 4-, and 5-chamber views. We employed DCNN algorithm to predict positive genotype based on the input echocardiographic images. We performed 5-fold cross-validations. We used 2 reference models—the Mayo HCM Genotype Predictor score (Mayo score) and the Toronto HCM Genotype score (Toronto score). We compared the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus DCNN-derived probability and the reference model. We calculated the p-value by performing 1,000 bootstrapping. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, we examined the net reclassification improvement. We included 99 adults with HCM who underwent genetic testing. Overall, 45 patients (45%) had positive genotype. The new model combining Mayo score and DCNN-derived probability significantly outperformed Mayo score (AUC 0.86 [95% CI 0.79–0.93] vs. 0.72 [0.61–0.82]; p < 0.001). Similarly, the new model combining Toronto score and DCNN-derived probability exhibited a higher AUC compared to Toronto score alone (AUC 0.84 [0.76–0.92] vs. 0.75 [0.65–0.85]; p = 0.03). An improvement in the sensitivity, specificity, PPV, and NPV was also achieved, along with significant net reclassification improvement. In conclusion, compared to the conventional models, our new model combining the conventional and DCNN-derived models demonstrated superior accuracy to predict positive genotype in patients with HCM.

The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders. J. Med. Invest. 68 : 189-191, February, 2021.

Background The prognosis of patients with cancer‐venous thromboembolism (VTE) is not well known because of a lack of registry data. Moreover, there is also no knowledge on how specific types are related to prognosis. We sought to evaluate the clinical characteristics and outcomes of patients with cancer‐associated VTE, compared with a matched cohort without cancer using real‐world registry data of VTE. Methods and Results This study was based on the Diagnosis Procedure Combination database in the JROAD‐DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Of 5 106 151 total patients included in JROAD‐DPC, we identified 49 580 patients who were first hospitalized with VTE from April 2012 to March 2017. Propensity score was estimated with a logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. After propensity matching, there were 25 148 patients with VTE with or without cancer. On propensity score‐matched analysis with 25 148 patients with VTE, patients with cancer had higher total in‐hospital mortality within 7 days (1.3% versus 1.1%, odds ratio [OR], 1.66; 95% CI, 1.31–2.11; P P P Conclusions Patients with cancer had a higher in‐hospital acute mortality for VTE than those without cancer, especially in pancreatic, biliary tract, and liver cancers.

Purpose Previous studies examined the right atrial (RA) input site of the antegrade fast pathway (AFp) (AFpI). However, the left atrial (LA) input to the atrioventricular (AV) node has not been extensively evaluated. In this study, we created three-dimensional (3-D) bi-atrial stimulus-ventricle (St-V) maps and analyzed the input site and characteristics of the AFp in both the RA and LA. Methods Forty-four patients diagnosed with atrial fibrillation or WPW syndrome were included in this study. Three-dimensional bi-atrial St-V mapping was performed using an electroanatomical mapping system. Sites exhibiting the minimal St-V interval (MinSt-V) were defined as AFpIs and were classified into seven segments, four in the RA (F, S, M, and I) and three in the LA (M1, M2, and M3). By combining the MinSt-V in the RA and LA, the AFpIs were classified into three types: RA, LA, and bi-atrial (BA) types. The clinical and electrophysiological characteristics were compared. Results AFpIs were most frequently observed at site S in the RA (34%) and M2 in the LA (50%), and the BA type was the most common (57%). AFpIs in the LA were recognized in 75% of the patients. There were no clinical or electrophysiological indicators for predicting AFpI sites. Conclusions Three-dimensional bi-atrial St-V maps could classify AFpIs in both the RA and LA. AFpIs in the LA were frequently recognized. There were no significant clinical or electrophysiological indicators for predicting AFpI sites, and 3-D bi-atrial St-V mapping was the only method to reveal the precise AFp input site.

Background The overlap time of transmitral flow can be a novel marker of subclinical left ventricular dysfunction for predicting adverse events in heart failure (HF). We aimed to (1) investigate the role of overlap time of the E-A wave in association with clinical parameters and (2) evaluate whether the overlap time could add prognostic information with respect to other conventional clinical prognosticators in HF. Methods We prospectively evaluated 153 patients hospitalized with HF (mean age 68 ± 15 years; 63% male). The primary endpoint was readmission following HF or cardiac death. Results During a median period of 25 months, 43 patients were readmitted or died. Overlap time appeared to be associated with worse outcomes. After adjustment for readmission scores and ratios of diastolic filling period and cardiac cycle length in a Cox proportional-hazards model, overlap time was associated with event-free survival, independent of elevated left atrial pressure based on guidelines. When overlap time was added to the model based on clinical variables and elevated left atrial pressure, the C-statistic significantly improved from 0.70 (95% CI: 0.63–0.77) to 0.77 (95% CI: 0.69–0.83, compared) (P = 0.035). Conclusion This preliminary study suggested that prolonged overlap time may have potential for predicting readmission and cardiac mortality risk assessment in patients with HF.

Funding Acknowledgements Type of funding sources: None. Background Ageing process per se is a major risk factor for heart failure (HF). In fact, the incidence of HF with preserved ejection fraction (HFpEF) dramatically increases with age. Although ageing plays a central role in the development of HFpEF, not all the elderly patients develop clinical HFpEF. Multiple abnormalities in the cardiovascular system have been proposed to contribute to the development of HFpEF. However, the pathophysiology that discriminates between physiological ageing and overt HFpEF is incompletely understood. Purpose The purpose of this study was to assess the effects of ageing on the cardiac structures and haemodynamics. Moreover, we evaluated the determinant factor that discriminates between physiological ageing and overt HFpEF by non-invasive preload increasing manoeuvre using leg-positive pressure (LPP) stress echocardiography. Methods A total of 91 subjects were prospectively recruited in this study: 22 patients with HFpEF and 69 healthy controls. Normal controls were further stratified into 3 age groups: young (n = 19, 20-40 years of age), middle-aged (N = 25, 40-65 years) and elderly (n = 25, >65 years). All subjects underwent LPP stress with a continuous external pressure of 90 mmHg around both lower limbs using dedicated airbags (Fig.). Results The left ventricular mass index (LVMI; young, 68 ± 19 g/m²; middle-age, 70 ± 18 g/m²; elderly, 84 ± 21 g/m²) and also the relative wall thickness (RWT; young, 0.34 ± 0.09; middle-age, 0.41 ± 0.06; elderly 0.55 ± 0.10) increased with ageing, which was accelerated in HFpEF (LVMI: 111 ± 32 g/m², RWT; 0.63 ± 0.19, ANOVA P Conclusions Striking parallels between structure-function alterations were observed in the physiological cardiovascular ageing process, which was further accelerated in patients with HFpEF. Not only structural remodeling and impaired diastolic function, but also impaired systolic reserve during preload stress is important haemodynamic feature that characterise the pathophysiology of HFpEF. Abstract Figure.

Heart failure with recovered ejection fraction (HFrecEF) has been reported in several previous studies to have a better prognosis than heart failure with reduced ejection fraction (HFrEF). However, the factors associated with HFrecEF have not been identified. The aim of this study was to test the hypothesis that left atrial (LA) strain could help identify patients with recovered ejection fraction (EF) among those with heart failure (HF) with low EF on admission.One hundred consecutive patients hospitalized for the first time for new-onset HF were enrolled. Patients were clinically diagnosed with HFrEF on admission (left ventricular EF 40%) and received optimal treatment for HF. Twenty-eight patients improved to HFrecEF during 6 months of follow-up.Regarding clinical background, there were significantly more women and a lower rate of atrial fibrillation in the HFrecEF group than in the HFrEF group. In a multivariate logistic regression analysis, LA strain was an independent predictor of HFrecEF, even after adjustment for gender and left ventricular EF (odds ratio: 4.06; 95% CI: 2.04-8.07; P .001). A cutoff value of 10.8% for LA strain showed high sensitivity (96%) and specificity (82%) in identifying HFrecEF in patients with HF presenting with low EF on admission. During a follow-up period of 24 ± 13 months, 31 patients (31%) had cardiovascular death or readmission for HF. Patients with reduced LA strain (10.8%) had significantly shorter event-free survival than those with preserved LA strain (P = .02).LA strain is a useful indicator for predicting HFrecEF and should be considered as a routine measurement in patients with HFrEF on admission.

Introduction: Genotyping may provide valuable insights into family screening strategies and prognosis in patients with hypertrophic cardiomyopathy (HCM). On the other hand, genotyping is expensive. Thus, it is important to identify patients who are more likely to be genotype positive. However, conventional prediction models (e.g., the Mayo score) based on clinical and echocardiographic parameters offer only modest accuracy and are subject to inter-observer variability. Hypothesis: Deep convolutional neural network (DCNN) analysis of echocardiographic images improves the ability to predict genotype positivity in HCM compared to the conventional model. Methods: We included 99 patients with HCM who underwent genetic testing for diagnostic and/or family screening purposes. The age at diagnosis was 46±20 years and 65% were male. In each case, we obtained parasternal short- and long-axis as well as all apical images at end-systole. The DCNN underwent 100 steps to develop the model to predict genotype positivity. In each step, we used 80% of the cohort as the training set and the remaining 20% as the test set (i.e., 5-fold cross-validation). We used the Mayo score as the reference model. We compared the area under the receiver operating characteristics curve (AUC) between a combined model using the reference model plus the DCCN-derived probability and the reference model. We calculated the p value by performing 1,000 bootstrapping. Results: Overall, 45 patients (45%) were genotype positive. The model combining the reference and the DCNN-derived models significantly outperformed the reference model (AUC 0.79 [95% CI 0.69-0.87] with the combined model vs. 0.72 [0.61-0.82] with the reference model; p=0.006; Figure). Conclusion: Compared to a conventional model based on clinical and echocardiographic parameters, our new model combining the conventional and DCNN-derived models demonstrated superior ability to predict positive genotype in patients with HCM.

Introduction: Chest X-ray (CXR) is a useful and economical modality for the detection of congestive heart failure. However, the accuracy is limited by the subjective nature of its interpretation. Deep learning (DL) can be used to recognize diseases or findings objectively in various imaging modalities, and may outperform previous diagnostic techniques. Hypothesis: We hypothesized that DL-based analysis of CXR detect the presence of elevated pulmonary arterial wedge pressure (PAWP) in patients with suspected heart failure. Methods: We enrolled 1,013 patients with paired right heart catheterization and CXR performed from October 2009 to February 2020 in our hospital. DL algorithm for the detection of elevated PAWP was developed using the training dataset, based on a single CXR image. Independent evaluation cohort of 115 patients was performed using CXR-based DL model and echocardiographic data to detect the presence of high PAWP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the DL-based models compared with echocardiographic data. Results: The study included 1,013 patients (mean age, 67±13 years; 569 males [56%]). The mean PAWP was 12.5±6.4 mmHg and 218 patients (22%) had more than 18mmHg. To detect high PAWP, the AUC produced by DL algorithms was effective, and the DL algorithm with the largest AUC was ResNet50. In an evaluation cohort, to detect high PAWP, the AUC using the DL model with CXR was similar to the AUC produced by the echocardiographic left ventricular diastolic dysfunction algorithm (0.77 vs. 0.70; respectively; p=0.27), and significantly higher than the AUC by measurements of echocardiographic parameters (ResNet50 vs. other parameters; all compared p (Figure) . Conclusions: The present results demonstrated that DL based on analysis of CXR can detect the presence of high PAWP. This finding suggests that the DL based approach may support an objective evaluation of CXR in the clinical setting.

Introduction: We sought to evaluate the clinical characteristics and outcomes of patients with cancer-associated VTE, compared with the matched cohort without cancer using real-world big data of VTE. Background: Cancer is associated with a high incidence of Venous Thromboembolism (VTE) and there are many guidelines/recommendations about VTE. However, the prognosis of cancer-VTE patients is not well known because of a lack of big data. Moreover, there is also no knowledge on how cancer type is related to prognosis. Methods: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). We identified 28,247 patients who were first hospitalized with VTE from April 2012 to March 2017. 26.0% were cancer patients. Compared with national statistics of cancer incidence in 2015 from National Cancer Center of Japan, the proportion of gynecological cancer patients was higher, but other cancer types had similar prevalence rates. Propensity score (PS) was estimated with logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. Results: We included 24,576 patients after exclusion. The median age was 71years (range: 59-80 years), and 42.0% were male. On PS-matched analysis with 12,418 patients, patients with cancer had higher total in-hospital mortality (9.5% vs. 3.8%, P Conclusions: Patients with cancer had a higher in-hospital mortality for VTE than those without cancer, especially in pancreatic, biliary tract and liver cancers.

Background: We have previously demonstrated local persistent hypercoagulation after durable polymer (DP)-sirolimus-eluting stent (SES) implantation by measuring plasma prothrombin fragment 1+2 (F1+2) levels. The aim of this study is to evaluate local coagulative response after newer-generation ultrathin strut SES implantation. Method: Forty-five patients who were treated about 6-12 months earlier with coronary stenting, with no evidence of restenosis, were studied [DP-SES (Cypher): 26pts, biodegradable polymer (BP)-SES (older BP-SES, Ultimaster): 12pts and ultrathin strut BP-SES (newer BP-SES, Orsiro): 7pts]. We measured plasma levels of F1+2 sampled in coronary sinus (CS) and sinus of Valsalva (V). The transcardiac gradient (Δ) was defined as CS level minus V level. Results: No significant difference was observed in the percent diameter stenosis among DP-SES, older BP-SES, and newer BP-SES groups (10.1 ± 16.5 vs 13.1 ± 12.9 vs 12.1 ± 11.9 %). The ΔF1+2 was significantly lower in the BP-SES groups than in the DP-SES group (8.9 ± 10.1 vs 23.4 ± 21.1 pmol/l, p Conclusion: Suppressed local coagulative response after newer-generation ultrathin strut SES implantation was observed. These findings might indicate that lower strut thickness is more important factor than faster polymer resorption in the newer-generation DES era.

Background Atrial fibrillation (AF) is the most common type of arrhythmia seen in clinical practice. Recent studies suggest that inflammation contributes to the pathogenesis of AF. On the other hand, several evidence suggests that toll-like receptor (TLR) 9 recognizes bacterial DNA, activating innate immunity, whereas it also provokes inflammation in response to fragmented DNA released from mammalian cells. Recently, we have reported that TLR 9 plays a pivotal role in the development of vascular inflammation and atherogenesis through proinflammatory activation of macrophages. Purpose This study aimed to assess whether TLR9 contributes to the AF arrhythmogenesis. Methods TLR9 deficient (TLR9−/−) and wild-type mice were infused with angiotensin II (Ang II) or vehicle via an osmotic minipump for 4 weeks. Blood pressure and body weight were measured serially. Then, we examined AF inducibility by intracardiac electrophysiological study and the inflammation-induced atrial remodeling by biochemical analysis after 4 weeks of Ang II infusion. Results There was no significant difference in blood pressure and pulse rate between TLR9−/− and wild-type mice both before and after Ang II infusion. Ang II-treated TLR9−/− mice showed lower incidence of AF compared with wild-type mice treated with Ang II. Genetic deletion of TLR9 significantly reduced the interstitial fibrosis in atrium of Ang II-treated mice. TLR9−/− mice also showed less mRNA expressions of inflammatory and fibrosis-related biomarkers (TNF-α, interleukin-6, TGF-β, collagen-1, collagen-3) in atrium compared with wild-type mice. Conclusions TLR9 might contribute to the AF arrhythmogenesis associated with atrial inflammation. TLR9 might serve as a potential therapeutic target for AF. Funding Acknowledgement Type of funding source: None

Background Early detection of pulmonary hypertension (PH) is crucial to ensure that patients receive timely treatment for the progressive clinical course. The chest X-ray (CXR), a routine method at hospitals, has recommended in order to reveal features supportive of a diagnosis of PH. However, it is well known that the sensitivity and specificity are low. Purpose We tested the hypothesis that application of artificial intelligence (AI) to the CXR could identify PH. Methods We retrospectively enrolled 900 data with paired CXR and right heart catheter (RHC), including the pulmonary artery pressure, from October 2009 to December 2018. We trained a convolutional neural network to identify patients with PH as actual value of pulmonary artery pressure, using the CXR alone (Figure). The diagnosis of PH was performed using hemodynamic measurements according to the most recent World Symposium standards: mean PAP ≥20 mmHg. We have compared the area under the curve (AUC) by human observers, measurements of CXR images, and AI for detection of PH. Results Subjects were divided into two groups with PH (439 patients; mean age, 66±14 years; 233 male) and without PH (461 patients; mean age, 68±12 years; 278 male). In an independent set, AI was the highest diagnostic ability for detection of PH (AUC: 0.71). The AUC by the AI algorithm was significantly higher than the AUC by measurements of CXR images and human observers (0.71 vs. 0.60 and vs. 0.63, all compared p Conclusion Applying AI to the CXR (a classical, universal, low-cost test) permits the CXR images to serve as a powerful tool to screen for PH. Neural network Funding Acknowledgement Type of funding source: None

Background: It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function.Methods: Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%.Results: First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116–117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects.Conclusions: Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.

Aims Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis. Methods and results Apolipoprotein E-deficient (Apoe−/−) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe−/− mice. Genetic deletion of Sting in Apoe−/− mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe−/− mice. In contrast, bone marrow-specific STING expression in Apoe−/− mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP. Conclusion Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.

Advanced age, obesity, and muscle weakness are independent factors in the onset of deep vein thrombosis (DVT). Recently, an association between sarcopenia and DVT has been reported. We hypothesized that sarcopenia related factors, observed by ultrasonography, are associated with the regression effect on the thrombus following anticoagulation therapy. The present study focused on gastrocnemius muscle (GCM) thickness and the GCM's internal echogenic brightness. We examined the association with DVT regression following direct oral anticoagulants (DOACs) treatment.The prospective cohort study period was between October 2017 and August 2018. We enrolled 46 patients diagnosed with DVT by ultrasonography, who were aged >60 years old and treated with DOACs. Sarcopenia was evaluated using the Asian Working Group for Sarcopenia flowchart. The average DOACs treatment period was 94 days, and 29 patients exhibited thrombus regression. On univariate logistic regression analysis, sarcopenia, average GCM diameter index, and gastrocnemius integrated backscatter index were significantly associated with thrombus regression. In a multivariate model, only the average GCM diameter index correlated with thrombus regression.The average GCM diameter index is associated with DVT regression treated with DOACs. Considering the GCM diameter during DVT treatment can be a marker to make a decision for the treatment of DVT.

Background Cardiac point-of-care ultrasound (POCUS) training has been integrated into medical school curricula. However, there is no standardized cardiac POCUS training method for medical students. To address this issue, the American Society of Echocardiography (ASE) proposed a framework for medical student cardiac POCUS training. The objective of this pilot study was to develop a medical student cardiac POCUS curriculum with test scoring systems and test the curriculum feasibility for a future definitive study. Methods Based on the ASE-recommended framework, we developed a cardiac POCUS curriculum consisting of a pre-training online module and hands-on training with a hand-held ultrasound (Butterfly iQ, Butterfly Network Inc., Guilford, CT, USA). The curriculum learning effects were assessed with a 10-point maximum skill test and a 40-point maximum knowledge test at pre-, immediate post-, and 8-week post-training. To determine the curriculum feasibility, we planned to recruit 6 pre-clinical medical students. We semi-quantitatively evaluated the curriculum feasibility in terms of recruitment rate, follow-up rate 8 weeks after training, instructional design of the curriculum, the effect size (ES) of the test score improvements, and participant satisfaction. To gather validity evidence of the skill test, interrater and test-retest reliability of 3 blinded raters were assessed. Results Six pre-clinical medical students participated in the curriculum. The recruitment rate was 100% (6/6 students) and the follow-up rate 8 weeks after training was 100% (6/6). ESs of skill and knowledge test score differences between pre- and immediate post-, and between pre- and 8-week post-training were large. The students reported high satisfaction with the curriculum. Both interrater and test-retest reliability of the skill test were excellent. Conclusions This pilot study confirmed the curriculum design as feasible with instructional design modifications including the hands-on training group size, content of the cardiac POCUS lecture, hands-on teaching instructions, and hand-held ultrasound usage. Based on the pilot study findings, we plan to conduct the definitive study with the primary outcome of long-term skill retention 8 weeks after initial training. The definitive study has been registered in ClinicalTrials.gov (Identifier: NCT04083924).

Recent development in artificial intelligence (AI) for cardiovascular imaging analysis, involving deep learning, is the start of a new phase in the research field. We review the current state of AI in cardiovascular field and discuss about its potential to improve clinical workflows and accuracy of diagnosis. In the AI cardiovascular imaging field, there are many applications involving efficient image reconstruction, patient triage, and support for clinical decisions. These tools have a role to support repetitive clinical tasks. Although they will be powerful in some situations, these applications may have new potential in the hands of echo cardiologists, assisting but not replacing the human observer. We believe AI has the potential to improve the quality of echocardiography. Someday AI may be incorporated into the daily clinical setting, being an instrumental tool for cardiologists dealing with cardiovascular diseases.

The key to understanding hemodynamics in heart failure (HF) is the relation between elevated left ventricular (LV) filling pressure and cardiac output. Some patients show abnormal response to stress in the relationship between LV filling pressure and cardiac output. In patients with preserved diastolic function, cardiac output can be increased without significantly elevated filling pressure during stress. In patients with HF, as long as the Frank-Starling mechanism operates effectively, cardiac output can increase while acquiring elevated filling pressure. In patients with decompensated HF, hemodynamic stress will lead to a much greater elevation in filling pressure and pulmonary venous hypertension.

There is a need to stratify patients who may develop heart failure because of the current "heart failure pandemic". We hypothesized that noninvasive assessment of diastolic electromechanical coupling by electrocardiography and Doppler echocardiography may be clinically useful for risk stratification of hypertensive patients who may develop heart failure.We measured the time from the peak to end of the T wave (TpTe) as an electrophysiological parameter, and peak early diastolic mitral flow (E) and lateral annular (e') velocities as mechanical parameters in 109 patients with hypertension. Relationships between these parameters and their association with the prognosis were evaluated.The e' was inversely correlated with TpTe (p 0.001) and QTc (p 0.014), whereas E/e' was positively correlated with TpTe (p 0.001) and QTc (p 0.001). The TpTe predicted patients with E/e' 12. There were 24 cardiovascular events during follow-up (57 ± 20 months), and Kaplan-Meier analysis showed that outcome was worse (p = 0.003) in patients with higher E/e' than lower E/e'; however, there was no difference between patients with longer TpTe (≧72 ms) and shorter TpTe ( 72 ms).The correlation of TpTe with e' and E/e' in hypertensive patients suggests that these parameters reflect diastolic ventricular electromechanical coupling. The E/e' predicted outcome, and an elevated E/e' should be suspected when TpTe is prolonged ( 72 ms). Noninvasive evaluation of diastolic electromechanical coupling is clinically useful in patients with hypertension for predicting their outcome.

BACKGROUND The coronary adventitia has recently attracted attention as a source of inflammation because it harbors nutrient blood vessels, termed the vasa vasorum (VV). This study assessed the link between local inflammation in adjacent epicardial adipose tissue (EAT) and coronary arterial atherosclerosis in fresh cadavers.Methods and Results:Lesion characteristics in the left anterior descending coronary artery of 10 fresh cadaveric hearts were evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), and the density of the VV and levels of inflammatory molecules from the adjacent EAT were measured for each of the assessed lesions. The lesions were divided into lipid-rich, lipid-moderate, and lipid-poor groups according to percentage lipid volume assessed by IB-IVUS. Higher expression of inflammatory molecules (i.e., vascular endothelial growth factor A [VEGFA] andVEGFB) was observed in adjacent EAT of lipid-rich (n=11) than in lipid-poor (n=11) lesions (7.99±3.37 vs. 0.45±0.85 arbitrary units [AU], respectively, forVEGFA; 0.27±0.15 vs. 0.11±0.07 AU, respectively, forVEGFB; P

At present, heart failure with preserved ejection fraction (HFpEF) is a commonly accepted condition in HF patients. In contrast to HF with reduced EF (HFrEF), HFpEF is strongly associated with aging, and vascular, metabolic, neurohormonal, and systemic inflammatory comorbidities. Two major hypotheses explain the pathophysiology of HFpEF (stages C,D in the American College of Cardiology Foundation/American Heart Association HF staging system): (1) impaired active relaxation and increased passive stiffness of the left ventricular (LV) myocardium during diastole (left atrial [LA]-LV coupling); and (2) LV and arterial stiffening during systole (LV-arterial coupling). Cardiac structural and functional abnormalities can be evaluated using non-invasive measures, such as 2-D, flow velocity Doppler, and tissue Doppler echocardiography, to estimate LV filling pressure and afterload mismatch. The clinical application of 2-D speckle-tracking echocardiography (2D-STE) is feasible for earlier diagnosis of functional abnormalities of the LA, LV, and elastic arteries in asymptomatic patients with cardiovascular risk factors (stages A,B). The goal of this review is to highlight the role of 2D-STE to detect impairment of LA-LV-arterial coupling beyond diastolic function earlier, because it may provide important information on the pathophysiology and prevention of HFpEF.

Background: The coagulation system is closely linked with vascular inflammation, although the underlying mechanisms are still obscure. Recent studies show that protease-activated receptor (PAR)-2, a major receptor of activated factor X, is expressed in both vascular cells and leukocytes, suggesting that PAR-2 may contribute to the pathogenesis of inflammatory diseases. Here we investigated the role of PAR-2 in vascular inflammation and atherogenesis. Methods: We generated apolipoprotein E-deficient ( ApoE -/- ) mice lacking systemic PAR-2 expression ( PAR-2 -/- ApoE -/- ). ApoE -/- mice, which lack or express PAR-2 only in bone marrow (BM) cells, were also generated by BM transplantation. Atherosclerotic lesions were investigated after 20 weeks on a Western-type diet by histological analyses, quantitative reverse transcription polymerase chain reaction, and Western blotting. In vitro experiments using BM-derived macrophages were performed to confirm the proinflammatory roles of PAR-2. The association between plasma activated factor X level and the severity of coronary atherosclerosis was also examined in humans who underwent coronary intervention. Results: PAR-2 -/- ApoE -/- mice showed reduced atherosclerotic lesions in the aortic arch ( P P P P P ApoE -/- mice. Systemic PAR2 deletion in ApoE -/- mice significantly decreased the expression of inflammatory molecules in the aorta. The results of BM transplantation experiments demonstrated that PAR-2 in hematopoietic cells contributed to atherogenesis in ApoE -/- mice. PAR-2 deletion did not alter metabolic parameters. In vitro experiments demonstrated that activated factor X or a specific peptide agonist of PAR-2 significantly increased the expression of inflammatory molecules and lipid uptake in BM-derived macrophages from wild-type mice compared with those from PAR-2–deficient mice. Activation of nuclear factor-κB signaling was involved in PAR-2–associated vascular inflammation and macrophage activation. In humans who underwent coronary intervention, plasma activated factor X level independently correlated with the severity of coronary atherosclerosis as determined by Gensini score ( P P Conclusions: PAR-2 signaling activates macrophages and promotes vascular inflammation, increasing atherosclerosis in ApoE -/- mice. This signaling pathway may also participate in atherogenesis in humans.

Background It has been recognized that a comprehensive cardiac rehabilitation (CR) program improves mortality in patients with chronic heart failure. On the other hand, the magnitude of the improvement in exercise capacity after CR differs among individuals. The aim of this study was to assess the echocardiographic determinants of responders to CR using preload stress echocardiography. Methods We prospectively enrolled 58 chronic heart failure patients with reduced left ventricular ejection fraction (aged 62 ± 11 years; 69% male; left ventricular ejection fraction 43% ± 7%) who had received optimized medical treatment in a CR program for 5 months. We performed preload echocardiographic studies using leg positive pressure (LPP) to assess the echocardiographic parameters during preload augmentation. We defined 41 patients as a development cohort to assess the predictive value of echocardiographic variables. Next, we validated results in the remaining 17 patients as a validation cohort. Results In the development cohort, significant improvement in peak oxygen uptake (VO2) (>10%) after CR was observed in 58% patients. In a multivariable logistic regression model, the significant predictor of improvement in exercise capacity was right ventricular (RV) strain during LPP (odds ratio: 3.96 per 1 standard deviation; P = 0.01). An RV strain value of −16% during LPP had a good sensitivity of 0.79 and a specificity of 0.71 to identify patients with improvement in peak VO2. In the validation cohort, an optimal cutoff value of RV strain value was the same (area under the curve: 0.77, sensitivity: 0.78, specificity: 0.65). Conclusions RV strain during LPP may be an echocardiographic parameter for assessing beneficial effects of CR.

Assessment of right ventricular (RV) function plays an important role in patients with cardiopulmonary disease, and current guidelines recommend parameters including tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic excursion velocity (RVS') to assess RV longitudinal function. We assessed the hypothesis that the previously undescribed motion of RV longitudinal rotation (RVLR) is an independent predictor of both TAPSE and RVS'.We assessed a series of 100 consecutive patients with pulmonary hypertension (PH) undergoing echocardiography. Patients with left ventricular (LV) dilation and dysfunction were excluded. Standard RV parameters were determined using established guidelines, while RVLR and right ventricular global longitudinal strain (RVGLS) measurements were performed using 2-dimensional (2D) speckle tracking technique.Mean peak RVLR measured -4.2±3.7 degrees. By convention, negative values implied clockwise motion. In a multiple linear regression model, TAPSE could be predicted from a combination of RVLR and RVGLS (R=0.56, P0.001). A similar relationship was found for RVS' which could also be predicted from a combination of RVLR and RVGLS (R=0.52, P0.001). While no association was found between RVLR and RV size, estimated RV systolic pressure (RVSP) or the presence of a pericardial effusion, a mild correlation was noted between RVLR and QRS duration (R=0.25, P=0.01).RVLR is an independent predictor of TAPSE and RVS'. Awareness of this motion should be considered in the interpretation of TAPSE and RVS' values as markers of RV systolic function, as abnormal RVLR may account for exaggerated values, particularly in patients with PH and RV dysfunction.