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Aims: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a noninvasive biomarker for pericoronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between PCAT attenuation and endothelial dysfunction assessed using flow-mediated dilation (FMD). Methods: A total of 119 outpatients who underwent both coronary CTA and FMD measurements were examined. PCAT attenuation values were assessed at the proximal 40-mm segments of all three major coronary arteries on coronary CTA. Endothelial function was assessed using FMD. Patients were then classified into two groups: those with endothelial dysfunction (FMD ＜4%, n=44) and those without endothelial dysfunction (FMD ≥ 4%, n=75). Results: In all three coronary arteries, PCAT attenuation was significantly higher in patients with endothelial dysfunction than in those without endothelial dysfunction. Multivariate logistic regression analysis revealed that PCAT attenuation in the right coronary artery (odds ratio [OR]=1.543; 95% confidence interval [CI]=1.004–2.369, p=0.048) and left anterior descending artery (OR=1.525, 95% CI=1.004–2.369, p=0.049) was an independent predictor of endothelial dysfunction. Subgroup analysis of patients with adverse CTA findings (significant stenosis and/or high-risk plaque) and those with coronary artery calcium score ＞100 showed that high PCAT attenuation in all three coronary arteries was a significant predictor of endothelial dysfunction. Conclusion: High PCAT attenuation was significantly associated with FMD-assessed endothelial dysfunction in patients with suspected coronary artery disease. Our results suggest that endothelial dysfunction is one of the pathophysiological mechanisms linking pericoronary inflammation to cardiac mortality.

Purpose: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) has emerged as a marker for pericoronary inflammation. We investigated the prognostic value of PCAT attenuation in patients with non-alcoholic fatty liver disease (NAFLD).Methods: We enrolled 232 patients with NAFLD and suspected coronary artery disease who underwent coronary CTA. NAFLD was defined by abdominal computed tomography (CT) as a ratio of hepatic attenuation to spleen attenuation of Results: During a median follow-up of 4.9 years, 17 patients experienced CV events. LAD-PCAT attenuation in patients with CV events was higher than that without CV events (−66.9±7.0 versus −70.5±6.6; p=0.032), while RCA-PCAT attenuation was not. LAD-PCAT attenuation and high-risk plaque features were independent predictors of CV events. The addition of LAD-PCAT attenuation to high-risk plaque features increased the C-statistics and global chi-square from 0.66 to 0.75 (p=0.042) and 6.8 to 12.7 (p=0.015), respectively. The net reclassification achieved by adding LAD-PCAT attenuation to the high-risk plaque features was 0.494 (p=0.041).Conclusion: High LAD-PCAT attenuation was an independent predictor of CV events in patients with NAFLD regardless of CTA-verified high-risk plaque features. Additionally, LAD-PCAT attenuation had incremental prognostic value over high-risk plaque features.

Background Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main limitation of its clinical application. Purpose The present study investigated the potential protective effect of sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, against DOX-induced cardiotoxicity in rats and H9c2 cells, and whether the underlying mechanism for any such protection involves its antioxidant activity. Methods Male Sprague-Dawley rats were randomly divided into four groups: DOX (1.5 mg/kg/day intraperitoneally for 10 days), DOX+valsartan (31 mg/kg/day by gavage from day 1 to day 18), DOX+sacubitril/valsartan (68 mg/kg/day by gavage from day 1 to day 18), and control (saline intraperitoneally for 10 days). There were 15 rats in each group. At the end of the treatment period, samples were collected and analysed. Cardiac function, tissue morphology, and reactive oxygen species (ROS) were evaluated in rats. Serum levels of Malondialdehyde (MDA) and cardiac troponin T were also measured. Mitochondrial ROS production and cell viability were evaluated in H9c2 cells. Results DOX-induced cardiac dysfunction was not prevented by valsartan and sacubitril/valsartan in this model. However, the serum level of cardiac troponin T on day 18 was increased in the DOX group (0.046±0.006 ng/mL, p Conclusions Sacubitril/valsartan protected rat hearts from DOX-induced cardiotoxicity in vivo and in vitro by decreasing oxidative stress. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This work was supported by Novartis Pharma K.K.

Background For the prevention of future cardiovascular events, control of residual risks such as triglyceride rich lipoproteins and HDL-cholesterol is an emerging problem beyond LDL-cholesterol. Triglyceride to HDL-cholesterol ratio (TG/HDL ratio) has been reported to be useful for risk classification of cardiovascular diseases. Meanwhile, several studies showed that high-risk plaque characteristics evaluated with coronary CT angiography (cCTA) was associated with the incidence of acute coronary syndrome. However, the relationship of TG/HDL ratio with coronary plaque characteristics and its impact of this association on future coronary events have not been fully elucidated. Purpose The aim of this study was to evaluate the association between TG/HDL ratio and high-risk plaque detected by cCTA and its impact on future coronary events. Methods A total of 944 patients suspected stable coronary artery disease who underwent cCTA at our institution were analyzed (mean 64-year-old, 55% male). Patients were divided into two groups by the median value of TG/HDL ratio (higher TG/HDL: TG/HDL ratio ≥2.0, lower TG/HDL: TG/HDL ratio 1.1) and spotty calcification. Cardiovascular event was defined as cardiovascular death, acute coronary syndrome, and late coronary revascularization after 30 days of CT acquisition. Results The higher TG/HDL ratio was significantly associated with male gender (63% vs. 48%, P Conclusion TG/HDL ratio is involved in the vulnerability of CT-verified coronary plaque characteristics. This association may play an important role in the prognostic impact of TG/HDL ratio on future cardiovascular events. Funding Acknowledgement Type of funding source: None

Background Abdominal aortic aneurysm (AAA) is a life-threatening disease, while effective and preventive medical treatments remain unestablished. Purpose The aim of this study was to evaluate the effect of selective peroxi- some proliferator-activated receptor alpha (PPARα) modulator pemafibrate on AAA formation in mice. Methods AAA was induced by subcutaneous infusion of angiotensin II (AngII) in apolipoprotein E-deficient mice for 4 weeks. Treatment by pemafibrate or vehicle was started one week before AngII infusion. Oxidative stress was evaluated by dihydroethidium (DHE) staining. Results Prognosis after AngII infusion in pemafibrate-treated mice was significantly better than that in vehicle-treated mice (log-rang test, p=0.035) by reducing the occurrence of fatal AAA rupture. Meanwhile pemafibrate did not significantly reduce maximal diameter of the aorta. Histological findings demonstrated that the expression of collagen in adventitia in pemafibrate-treated mice was significantly greater than that in vehicle-treated mice (p Conclusion Pemafibrate reduced the rupture of AAA in this murine model, which is associated with anti-oxidative stress via catalase induction. Funding Acknowledgement Type of funding source: None

There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians.

Background Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients. Methods This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio Results Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82–10.44, p 2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p Conclusions NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events.

To select the best revascularization strategy a correct understanding of the ischemic territory and the coronary anatomy is crucial. Stress myocardial perfusion single photon emission computed tomography (SPECT) is the gold standard to assess ischemia, however, SPECT has important limitations such as lack of coronary anatomical information or false negative results due to balanced ischemia in multi-vessel disease. Angiographic scores are based on anatomical characteristics of coronary arteries but they lack information on the extent of jeopardized myocardium. Cardiac computed tomography (CCT) has the ability to evaluate the coronary anatomy and myocardium in one sequence, which is theoretically the ideal method to assess the myocardial mass at risk (MMAR) for any target lesion located at any point in the coronary tree. In this study we analyzed MMAR of the three main coronary arteries and three major side branches; diagonal (Dx), obtuse marginal (OM), and posterior descending artery (PDA) in 42 patients with normal coronary arteries using an algorithm based on the Voronoi method. The distribution of MMAR among the three main coronary arteries was 44.3 ± 5.6 % for the left anterior descending artery, 28.2 ± 7.3 % for the left circumflex artery, and 26.8 ± 8.6 % for the right coronary artery. MMAR of the three major side branches was 11.3 ± 3.9 % for the Dx, 12.6 ± 5.2 % for the OM and 10.2 ± 3.4 % for the PDA. Intra- and inter-observer analysis showed excellent correlation (r = 0.97; p

High diagnostic performance of noninvasive fractional flow reserve computed from CT (FFR-CT) was recently reported in prospective multicenter trials. The aims of this study were to evaluate the diagnostic accuracy of FFR-CT in clinical practice and to examine the lesion characteristics showing a mismatch between FFR-CT and invasive FFR. A total of 20 patients (29 vessels) with suspected coronary artery disease were included. All patients underwent invasive coronary angiography and invasive FFR according to coronary artery CT angiography (CCTA) findings. The same raw data used for CCTA were used to evaluate FFR-CT. Results from FFR-CT were compared with invasively measured FFR. A positive ischemia was defined as FFR

Background: The myocardial mass at risk (MMAR), representing volume of myocardium distal to culprit lesion, is one of important factors for predicting adverse cardiac event in ischemic heart disease. However, current non-invasive cardiac imaging fails to quantify MMAR in patients with stable coronary artery disease. We have developed a new software calculating MMAR of any designated coronary artery by reconstructing the 3-dimensional-volume-data of cardiac computed tomography (CCT). The novel index, ratio of MMAR to whole left ventricular volume (%LV-MMAR), calculated with this software would be appealing to obtain MMAR objectively. This study aims to compare the %LV-MMAR with Bypass Angioplasty Revascularization Investigation (BARI) and modified Albert Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores, both of which are invasive angiographic methods widely used to estimate MMAR, in patients with single-vessel disease. Methods: Between April 2008 and March 2014, patients suspected of effort angina pectoris without history of previous myocardial infarction were assessed with CCT and invasive coronary angiography. Of those, 48 patients who were revealed single-vessel disease (left anterior descending artery (LAD): n=22, left circumflex artery (LCX): n=11 and right coronary artery (RCA): n=15) were included in this study. %LV-MMAR was calculated on the software. BARI and modified APPROACH score were calculated and compared with %LV-MMAR. Results: Mean %LV-MMAR was 27.6 [18.2-37.1] %. BARI and APPROACH scores showed a significant correlation (r=0.92, p Conclusions: This study revealed %LV-MMAR, calculated from CCT data on novel software, to be a promising index for estimating perfusion territory noninvasively in good agreement with BARI and modified APPROACH score.

The aim of the present study was to evaluate the factors related to poor prognosis of out-of-hospital cardiac arrest patients in one local area of Japan. From May 1, 2002 to April 30, 2008, a total of 442 patients with cardiopulmonary arrest were transferred for resuscitation to the National Hospital Organization, Iwakuni Clinical Center. Of 325 patients with cardiopulmonary arrest of cardiac etiology, 126 patients were witnessed by a bystander. However, only 37 received bystander cardiopulmonary resuscitation, 13 had shockable cardiac rhythm, 3 survived 1 month, and 2 had a good neurological discharge. Multivariate analysis of overall cardiac arrest showed that 1-month survival and neurologically favorable discharge were associated with bystander cardiopulmonary resuscitation (P = 0.049 and 0.013) and initial shockable cardiac rhythm (P = 0.001 and 0.007). In this region, the survival rate for patients with cardiopulmonary arrest was lower than that reported in other areas, probably because fewer patients received bystander CPR or had shockable cardiac rhythm. This may result from CPR being less popularized in this region than in other areas, suggesting that raising the awareness of CPR would improve the survival rate.

The myocardial mass at risk (MMAR), representing volume of myocardium distal to culprit lesion, is important in predicting adverse cardiac event. However, non-invasive cardiac imaging fails to quantify MMAR in patients with stable coronary artery disease. We have developed a new software based on