Low-Attenuation Coronary Plaque Volume and Cardiovascular Events in Patients with Distinct Metabolic Phenotypes with or without Diabetes.

Background: Diabetes mellitus (DM) plays a key role in the pathophysiology of metabolic syndrome (MetS). This study aimed to investigate the association among DM, low-attenuation plaque (LAP) volume, and cardiovascular outcomes across metabolic phenotypes in patients with suspected coronary artery disease (CAD) who underwent coronary computed tomography angiography (CCTA). Methods: We included 530 patients who underwent CCTA. MetS was defined as the presence of a visceral adipose tissue area ≥ 100 cm 2 in patients with DM (n = 58) or two or more MetS components excluding DM (n = 114). The remaining patients were categorised as non-MetS patients with DM (n = 52) or without DM (n = 306). A CCTA-based high-risk plaque was defined as a LAP volume of > 4%. The primary endpoint was the presence of a major cardiovascular event (MACE), which was defined as a composite of cardiovascular death, acute coronary syndrome, and coronary revascularization. Results: The incidence of MACE was the highest in the non-MetS with DM group, followed hierarchically by the MetS with DM, MetS without DM, and non-MetS without DM groups. In the multivariable Cox hazard model analysis, DM as a predictor was associated with MACE independent of LAP volume > 4% (hazard ratio, 2.68; 95% confidence interval, 1.16-6.18; p = 0.02), although MetS did not function as an independent predictor. A LAP volume > 4% functioned as a predictor of MACE, independent of each metabolic phenotype or DM. Conclusions: This study demonstrated that DM, rather than MetS, is a predictor of coronary events independent of high-risk plaque volume in patients who underwent CCTA.

Usefulness of pre- and post-stent optical frequency domain imaging findings in the prediction of periprocedural cardiac troponin elevation in patients with coronary artery disease.

Cholesterol crystals (CCs) are frequently found in high-risk plaques, such as thin-capped fibroatheromas. The purpose of this study was to investigate the associations of CCs, plaque morphologies, and post-stent optical frequency domain imaging (OFDI) findings with periprocedural cardiac troponin (cTn) elevation in patients treated with percutaneous coronary intervention (PCI). This study consists of 119 patients with stable coronary artery disease (CAD) with normal cTn levels who underwent OFDI-guided PCI. Periprocedural cTn elevation was defined as an elevation of cTn ≥ × 5 times the upper reference limit after PCI. Pre- and post-stent OFDI findings, including fibrous cap thickness (FCT), presence of CCs, and parameters for lipid and calcification were analyzed. A total of 37 (31%) patients were classified into the periprocedural cTn elevation group. Compared with lesions without CCs, lesions exhibiting CCs had thinner FCT, larger lipid arc, and longer lipid length, and were more likely to have irregular protrusion and in-stent thrombus (all p < 0.05). For pre-stent OFDI features, FCT < 82 µm [odds ratio (OR) 4.11; p = 0.003] and CCs (OR 3.23; p = 0.017) were associated with periprocedural cTn elevation. For post-stent OFDI features, in-stent dissection (OR 3.08; p = 0.035) and in-stent thrombus (OR 7.98; p = 0.002) were independent predictors of cTn elevation. The combination of CCs and FCT < 82 µm showed increased risk of periprocedural cTn elevation (OR 7.22; p = 0.002). OFDI-guided PCI provides unique insight into the mechanism for periprocedural cTn elevation in CAD patients.

Prognostic significance of renal dysfunction and its change pattern on outcomes in patients with acute coronary syndrome treated with emergent percutaneous coronary intervention.

Renal dysfunction and its change pattern are associated with short- and long-term mortality. However, it remains to be investigated whether or not worsening renal function (WRF) defined by baseline renal function identified from different time points would provide prognostic implication on outcomes in acute coronary syndrome (ACS) patients. This study consists of 334 ACS patients (mean age 68 ± 11 years, 75% male) treated with emergent percutaneous coronary intervention (PCI). Estimated glomerular filtration rate (eGFR) was evaluated on baseline, during hospitalization, at discharge, and at 3-month follow-up. WRF was defined as a relative decrease of eGFR > 20% at 3 months using baseline eGFR identified from different time points. The primary end point was a composite event of major cardiovascular events (MACE), including all-cause death, ACS, and heart failure hospitalization. The associations of chronic kidney disease (CKD), acute kidney injury (AKI), and WRF with MACE were evaluated. During a mean follow-up of 3.3 ± 1.7 years, a total of 64 MACE were observed. Multivariable analysis revealed that CKD (hazard ratio 2.16; p = 0.018) and AKI (hazard ratio 1.95; p = 0.030) were independent predictors of MACE, but WRF did not remain as an independent predictor of MACE (p = 0.208). The highest risk was observed in AKI patients with CKD when stratified by the presence or absence of CKD and AKI. In ACS patients treated with emergent PCI, this study demonstrated that CKD and AKI were independent predictors of MACE, while there was no independent relationship between WRF and MACE.

Clinical significance of discrepant mid-wall late gadolinium enhancement in patients with nonischemic dilated cardiomyopathy.

A drawback of visual assessment for late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is the subjectivity and reproducibility of the results. The aim of this study was to investigate the relationship between left ventricular (LV) reverse remodeling in response to optimal pharmacotherapies and the definite or discrepant mid-wall LGE with visual assessment in patients with dilated cardiomyopathy (DCM). A total of 65 patients who had been hospitalized with newly diagnosed DCM and had undergone CMR, were enrolled. When the visual assessment of the presence or absence of mid-wall LGE was confirmed by the two observers, patients were classified into either the positive- (n = 20) or negative-LGE (n = 29) groups. If there was discordance between the diagnoses of the two observers, patients were classified into the discrepant-LGE (n = 16) group. LV reverse remodeling was defined as an increase in LV ejection fraction by at least 10% concomitant with a decrease in the LV end-diastolic dimension by at least 10%. Among the three groups, the frequency of early LV reverse remodeling within a 1-year follow-up was significantly different (p = 0.0068). The frequency of LV reverse remodeling within a 1-year follow-up was 59, 31, and 15%, and over 2 years was 83, 62, and 40%, in patients with negative-, discrepant-LGE, and positive-LGE, respectively. The survival rate for composite end-points of cardiovascular mortality, sustained ventricular tachycardia, appropriate cardioverter-defibrillator discharge, or rehospitalization for decompensated heart failure was lower in positive-LGEs than in negative-LGEs (p =0.0011), whereas, there were no significant differences between both negative- and discrepant-LGEs, and discrepant- and positive-LGEs. This study showed that the discordance for LGE visual assessment occupied an intermediate position between positive and negative for LGE in LV reverse remodeling in patients with DCM.

Associations of sensitive cardiac troponin-I with left ventricular morphology, function and prognosis in end-stage renal disease patients with preserved ejection fraction.

Sensitive cardiac troponin I (cTnI) predicts all-cause and cardiovascular mortality in various clinical settings. However, its clinical significance in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF) has not been fully elucidated. This study investigated the association of cTnI with LV morphology and function, and its long-term outcome in HD patients with preserved LVEF. This prospective study consists of 96 HD patients with preserved LVEF (69 ± 8 years and 63% male) who underwent two-dimensional echocardiographic examination and biomarker tests including cTnI, brain natriuretic peptide, and high-sensitive C-reactive protein. The primary endpoint was all-cause death and secondary endpoint was cardiovascular death. Factors independently associated with cTnI were systolic blood pressure (ß = - 0.239, p = 0.011), heart rate (ß = 0.216, p = 0.021), LV mass index (ß = 0.231, p = 0.020), and E to e' ratio (ß = 0.237, p = 0.016). During a mean follow-up of 3.6 years, primary and secondary endpoints were observed in 23 (24%) and 18 (19%) patients, respectively. In the multivariate Cox proportional hazard analysis, the upper cTnI tertile has significantly increased risk of all-cause mortality [hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.139-6.386; p = 0.024] and that of cardiovascular death (HR, 4.56; 95% CI 2.021-16.968; p = 0.006) independent of echocardiographic measures and other serum biomarkers. In HD patients with preserved LVEF, serum cTnI levels were significantly associated with diastolic function and risk of mortality independent of echocardiographic variables and other biomarkers.

Association between duration of coronary occlusion and high-intensity signal on T1-weighted magnetic resonance imaging among patients with angiographic total occlusion.

OBJECTIVES: To evaluate the association between duration of the coronary occlusion and high-intensity signal (HIS) on noncontrast T1-weighted imaging using a 1.5-T magnetic resonance imager among patients with angiographic coronary total occlusion. METHODS: The signal intensity of the coronary target area divided by the signal intensity of the left ventricular muscle near the target area at each site (TMR) was measured. Areas with a TMR >1.0 were defined as HIS. Thirty five lesions from 33 patients were divided into the following three groups: subacute occlusion (up to 3 months; n = 7), short-duration chronic total occlusion (SD-CTO: 3-6 months; n = 9) and long-duration CTO (LD-CTO: ≥6 months; n = 19). RESULTS: All subacute occlusion lesions showed a HIS within the occlusion site. Among patients with CTO, the frequency of a HIS within the occlusion site was significantly higher in SD-CTO than in LD-CTO lesions (p = 0.013). In multivariate analyses, only an occlusion duration of less than 6 months was an independent factor associated with the presence of HIS (odds ratio 7.6, 95% CI 1.1-54.5; p = 0.044). CONCLUSIONS: The presence of a HIS in the occlusion site was associated more with SD-CTO than with LD-CTO among patients with CTO. KEY POINTS: • All subacute occlusion lesions show a high-intensity signal on T1-weighted imaging. • HIS within occlusion sites is associated with subacute or short-duration total occlusion. • T1-weighted imaging for coronary total occlusion may be useful for intervention strategy.

High-sensitive cardiac troponin T as a novel predictor for recurrence of atrial fibrillation after radiofrequency catheter ablation.

AIMS: We aimed to determine whether elevated serum high-sensitive cardiac troponin T (hs-TnT) levels predict atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). METHODS AND RESULTS: We included 125 consecutive patients with AF (paroxysmal, n = 79; persistent, n = 46) who underwent first-time PVI. Serum hs-TnT, high-sensitive C-reactive protein (hs-CRP), atrial natriuretic peptide, and plasma B-type natriuretic peptide levels were measured in venous samples collected before PVI. Elevated hs-TnT was diagnosed in patients with levels ≥0.014 µg/L. All patients underwent multidetector computed tomographic examinations before PVI to measure left atrial volume (LAV) and left ventricular (LV) mass, which were indexed to body surface area. Arrhythmia recurrence was defined as AF/atrial tachycardia episodes lasting for ≥30 s after a 2-month blanking period from the PVI procedure. Elevated hs-TnT levels were observed in 22 (17.6%) patients. Age, diabetes mellitus, LV mass index, estimated glomerular filtration rate, and hs-CRP were independently associated with serum hs-TnT levels (all P < 0.05). During a mean follow-up of 12.9 ± 8.5 months after a single PVI procedure, the clinical recurrence rate was 33% (n = 41). Multivariate Cox proportional hazard analysis revealed that a greater LAV index (P = 0.01) and elevated serum hs-TnT level (P = 0.01) were significant predictors of AF recurrence after PVI. CONCLUSION: This study demonstrated that elevated serum hs-TnT levels are associated with AF recurrence independent of traditional risk factors and left atrial enlargement.

Coronary plaque rupture with subsequent thrombosis typifies the culprit lesion of non-ST-segment-elevation myocardial infarction, not unstable angina: non-ST-segment-elevation acute coronary syndrome study.

Recently, unstable angina pectoris (UAP) and non-ST-segment-elevation myocardial infarction (NSTEMI) have been considered together because they exhibit indistinguishable clinical and electrocardiogram features, and constitute non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). However, no optical coherence tomography (OCT) studies have reported the association between vulnerable plaque morphology and clinical characteristics in NSTE-ACS patients based on assessment of clinical symptoms and myocardial necrosis. The aim of this study was to investigate the differences in clinical characteristics and plaque morphology assessed by OCT between patients with UAP and NSTEMI. Preinterventional OCT images of 84 NSTE-ACS patients were studied, 19 with NSTEMI and 65 with UAP, according to levels of high-sensitivity troponin T. The frequency of plaque rupture and thrombus in patients with NSTEMI was higher than in UAP patients with either class I or II + III (rupture: NSTEMI, 68 %; UAP classes II + III, 30 %; UAP class I, 19 %, thrombus: NSTEMI, 73 %; UAP classes II + III, 22 %; UAP class I, 14 %). In NSTEMI patients, the frequency of occurrence of both thrombus and rupture was the highest. Conversely, patients with UAP class I or those with UAP classes II + III most frequently had no thrombus and rupture, and the frequencies of the presence of thrombus were only 14 and 22 %, respectively. Multivariate analysis revealed that thrombus and plaque rupture were independently associated with NSTEMI. This study demonstrates that the morphological features of culprit lesions could be related to clinical severity in NSTE-ACS patients.

Epicardial Adipose Tissue Accumulation Is Associated With Renal Dysfunction and Coronary Plaque Morphology on Multidetector Computed Tomography.

BACKGROUND: Chronic kidney disease (CKD) is strongly associated with coronary artery disease (CAD), although the underlying pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) has recently been recognized as an important source of various pro-inflammatory cytokines causing coronary atherosclerosis. This study investigated the relationship between CKD and EAT volume in association with high-risk plaque. METHODS AND RESULTS: The study included 275 patients with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m(2)who underwent multidetector computed tomography (MDCT) for the evaluation of CAD. Patients were classified, according to eGFR, into a CKD group (30≤eGFR<60 ml/min/1.73 m(2)) or a non-CKD group (eGFR ≥60 ml/min/1.73 m(2)). MDCT was used to assess coronary plaque morphology and EAT volume. One hundred and ten patients with CKD were more likely to be older, have higher prevalence of hypertension, lower serum HDL-C, higher serum CRP, and larger EAT volume, than those without CKD (all P<0.01). On multivariate analysis age, hypertension, and EAT volume were significantly associated with eGFR (all P<0.01). EAT volume was associated with the presence of high-risk plaque, independent of traditional CAD risk factors (P=0.003). CONCLUSIONS: Patients with CKD had significantly increased EAT volume, which could be associated with the presence of high-risk plaque.

Characteristic patterns of the longitudinal and circumferential distribution of calcium deposits by parent coronary arteries observed from computed tomography angiography.

Many investigators have reported that the total amount of coronary calcium correlates with the overall magnitude of atherosclerotic plaque burden in the entire coronary tree and is a powerful predictor of future cardiovascular events. However, the development and spatial distribution of coronary calcifications remain unclear. We investigated the spatial distribution of calcifications throughout the coronary tree during coronary artery evaluation using coronary computed tomography angiography (CTA). A further aim was to assess the progression of existing calcifications and the development of new deposits in a follow-up study. The study population consisted of 287 patients for the cross-sectional study using CTA to evaluate the spatial distribution of calcifications by parent coronary arteries. Next, we analyzed a CTA dataset of 57 patients who had undergone two CTA examinations. In this group, the two CTA images were used for assessing the progression of existing calcifications and the development of new deposits. The coronary calcifications tended to be clustered within the proximal and middle portions. Moreover, in the proximal left anterior descending coronary artery (LAD), small calcifications were located more toward the inner pericardial side. Finally, new calcium deposits developed within the proximal and middle portions of the LAD and left circumflex coronary artery, but those in the right coronary artery were likely to appear evenly from the proximal to the distal portion. This study shows the characteristic patterns of the longitudinal and circumferential distribution of calcifications by parent coronary arteries.

New insights into spotty calcification and plaque rupture in acute coronary syndrome: an optical coherence tomography study.

Although recent optical coherence tomography (OCT) studies have focused on spotty calcification, whether there were any characteristics in the concomitant existence of calcification and plaque rupture remains unknown. The aim of the present study was to investigate the characteristics of spotty calcification in acute coronary syndrome (ACS) patients with or without plaque rupture, using OCT. This study enrolled 98 consecutive patients with ACS. OCT image acquisitions were performed in the culprit lesions, and patients were divided into the plaque rupture group (n = 38) and the non-rupture group (n = 60). The frequency of spotty calcification (p = 0.006), thin-capped fibroatheroma (p = 0.012), macrophage infiltration (p = 0.022), and the number of spotty calcification per patient (p < 0.001) were significantly higher and the largest arc and the minimum depth of spotty calcification from the luminal surface were significantly smaller in the rupture group. Moreover, in the rupture group, most of the spotty calcifications in the site nearest to the minimum lumen area were observed in the proximal portion of that site, and tended to be located near the plaque rupture. Multivariate analysis revealed that the presence of spotty calcification (OR 3.19, 95 % CI 1.12-9.76, p = 0.030) and age (OR 1.08, 95 % CI 1.02-1.14, p = 0.008) were independent predictive factors for plaque rupture. This study demonstrates the characteristics of spotty calcification in ACS patients with plaque rupture and the positional relationship between spotty calcification and plaque rupture. These detailed observations could impact on treatment strategies for the prevention of ACS.

The Clinical Value of High-Intensity Signals on the Coronary Atherosclerotic Plaques: Noncontrast T1-Weighted Magnetic Resonance Imaging.

Over the past several decades, significant progress has been made in the pathohistological assessment of vulnerable plaques and in invasive intravascular imaging techniques. However, the assessment of plaque morphology by invasive modalities is of limited value for the detection of subclinical coronary atherosclerosis and the subsequent prediction or prevention of acute cardiovascular events. Recently, magnetic resonance (MR) imaging technology has reached a sufficient level of spatial resolution, which allowed the plaque visualization of large and static arteries such as the carotids and aorta. However, coronary wall imaging by MR is still challenging due to the small size of coronary arteries, cardiac and respiratory motion, and the low contrast-to-noise ratio between the coronary artery wall and the surrounding structures. Following the introduction of carotid plaque imaging with noncontrast T1-weighted imaging (T1WI), some investigators have reported that coronary artery high-intensity signals on T1WI are associated with vulnerable plaque morphology and an increased risk of future cardiac events. Although there are several limitations and issues that need to be resolved, this novel MR technique for coronary plaque imaging could influence treatment strategies for atherothrombotic disease and may be useful for understanding the pathophysiological mechanisms of atherothrombotic plaque formation.

Cardio-ankle Vascular Index Associated with Coronary Plaque Burden not Plaque Morphology.

Background Cardio-ankle vascular index (CAVI) is a marker that reflects the overall stiffness of the aorta, femoral artery, and tibial artery. Several previous reports have shown the usefulness of CAVI for coronary artery disease (CAD) presence and severity. According to coronary angiography (CAG) and intracoronary imaging such as optical coherence tomography (OCT), coronary plaque burden and morphology as predictors of all-cause and cardiovascular mortality were previously evaluated. The aim of our study was to assess the correlation between CAVI value and Gensini's score for the coronary plaque burden as well as CAVI value and plaque morphology by using OCT. Methods A total of 548 consecutive patients who underwent CAG were enrolled in this study. CAVI value was evaluated in all patients, and OCT was performed in 89 of the 548 patients. CAVI ratio is calculated as CAVI/CAVIex (expected normal value of CAVI, which is calculated using patient age and sex). Results On multivariable analysis, sex, age, hypertension, diabetes mellitus, and CAVI were significantly correlated with logarithmized Gensini's score. CAVI values were significantly higher in the groups with CAD, which were 1 vessel disease (VD), 2VD, and 3VD, than in the OVD group (p<0.001). However, there was no statistical significance between CAVI ratio and OCT findings in terms of plaque morphology. Conclusions CAVI might be useful as a routine test for the detection of CAD and the evaluation of atherosclerotic plaque burden but not coronary plaque vulnerability.

Comparison of effects of sitagliptin and voglibose on left ventricular diastolic dysfunction in patients with type 2 diabetes: results of the 3D trial.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor (DPP-4i) attenuates postprandial hyperglycemia (PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes. METHODS: We conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin (50 mg/day) or voglibose (0.6 mg/day). The primary endpoints were changes in the e' velocity and E/e' ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers. RESULTS: The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e' velocity and E/e' ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e' and E/e' ratio. Among patients not using pioglitazone, e' increased and the E/e' ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group (4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (-0.7 ± 0.6 % vs. -0.3 ± 0.4, p < 0.005; -1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups. CONCLUSIONS: Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes. TRIAL REGISTRATION: Registered at http://www.umin.ac.jp under UMIN000003784.

Percutaneous carbon dioxide mist treatment has protective effects in experimental myocardial infarction.

Percutaneous treatment with carbon dioxide (CO2) mist, CO2 gas dissolved in water, contributes to improved cardiac function after myocardial infarction (MI). In this study, we investigated the effects of repeated pretreatment with CO2 mist on cardiac dysfunction after MI. The CO2 mist was generated by a dry mist production unit. The whole body of rats below the axilla was wrapped in a polyethylene bag, which was sealed and filled with the CO2 mist in the draft cabinet for 30 min daily for 7 days. MI was induced by ligation of the coronary artery in untreated (UT), CO2 gas-pretreated (CG), and CO2 mist-pretreated (CM) rats. The infarct size and the increase in oxidative stress due to MI were significantly smaller in the CM rats than in the UT rats. Furthermore, the expression of inflammation-related genes, such as monocyte chemoattractant protein-1, and fibrosis-related genes, such as transforming growth factor-ß1, was significantly suppressed in the CM rats. The CM rats had a better left ventricular ejection fraction than the UT rats 7 days after MI. These parameters in the CG rats were the same as in the UT group. Thus, CO2 mist preparative treatment may be potentially useful for the reduction of MI.

Clinical Characteristics of Late Gadolinium Enhancement in Patients with Cardiac Sarcoidosis.

BACKGROUND: The presence of cardiac involvement in sarcoidosis, a multisystem granulomatous disease of unknown etiology, is associated with very poor prognosis. Therefore, early detection of cardiac sarcoidosis (C-sar) is very important for effective treatment. Recently, the value of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), which allows visualization of even minute amounts of myocardial damage, has been emphasized in diagnosing C-sar. Although the presence of LGE has been added as a minor criterion for diagnosing C-sar in the most recent Japan Ministry of Health and Welfare (JMHW) guidelines, its clinical utility remains unknown. METHODS: A total of 17 patients with biopsy-proven extracardiac sarcoidosis, who underwent CMR and examinations using a sufficient number of modalities to diagnose or exclude C-sar in accordance with the JMHW diagnostic criteria, were retrospectively enrolled in this study. Among these 17 patients, 7 patients were diagnosed with C-sar and 10 with non-C-sar. We investigated the clinical performance of LGE in the detection of cardiac involvement, compared the distribution of LGE with perfusion defects of iodine-123-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) or thallium-201 (201Tl) scintigraphy, and evaluated the prognostic value of LGE on CMR in identifying adverse clinical events. RESULTS: All patients diagnosed with C-sar were positive for LGE and all diagnosed with non-C-sar patients were negative. Evaluation of LGE revealed a broader range of abnormalities than the evaluation of the defects shown by either BMIPP or 201Tl scintigraphy. All adverse events occurred in the C-sar patients with LGE. CONCLUSIONS: This study showed that LGE is useful for the detection of cardiac involvement, and it might be a promising tool for determining the prognosis of patients with biopsy-proven extracardiac sarcoidosis.

Vascular Functional and Morphological Alterations in Smokers during Varenicline Therapy.

BACKGROUND: Varenicline has been reported to achieve high rates of smoking cessation. It remains undetermined whether varenicline therapy improves vascular function in smokers. METHODS: Consecutive Seventy-two smokers (age 57 ± 12 years) who succeeded in complete smoking cessation and 46 normal healthy volunteers (age 24 ± 3 years) with no cardiovascular risk factors were enrolled into this study. Vascular function and structure were assessed by flow-mediated dilation (FMD), nitroglycerin-induced vasodilation, and brachial artery intima-media thickness (baIMT) at baseline and 20 weeks after the initiation of varenicline therapy in smokers. FMD and baIMT were measured simultaneously using a semi-automatic vessel wall-tracking software program. 75 µg dose of a nitroglycerin tablet were sublingually administered for the nitroglycerin-induced vasodilation measurement. RESULTS: Exhaled-carbon monoxide concentration decreased significantly (20.0 ± 11.1 ppm at baseline vs 1.9 ± 1.5 ppm after 20 weeks, p < 0.001). FMD was significantly improved after 20 weeks (4.09% ± 1.83% at baseline vs 4.77% ± 2.33% after 20 weeks, p = 0.010), whereas nitroglycerin-induced vasodilation and baIMT were not significantly changed. CONCLUSIONS: Smoking cessation with varenicline therapy significantly increased FMD without significant changes of nitroglycerin-induced vasodilation or baIMT from baseline to 20 weeks. It appears to improve vascular function in smokers, which depends on endothelial function rather than on vascular smooth muscle function or changes in vascular structure.

DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study.

BACKGROUND: Alpha glucosidase inhibitor (GI) attenuates postprandial hyperglycemia (PPH) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes. Dipeptidyl peptidase 4 (DPP-4) inhibitors also attenuate PPH. PPH is one of the factors leading to endothelial dysfunction which is an early event in the pathogenesis of atherosclerosis. Furthermore, DPP-4 inhibitors protect endothelial function through a GLP-1-dependent mechanism. However, the impact of these two types of drugs on endothelial dysfunction in patients with type 2 diabetes has not been fully elucidated. We compared the effects of sitagliptin, a DPP-4 inhibitor, and voglibose, an alpha GI, on endothelial function in patients with diabetes. METHODS: We conducted a randomized prospective multicenter study in 66 patients with type 2 diabetes who did not achieve the treatment goal with sulfonylurea, metformin or pioglitazone treatment; 31 patients received sitagliptin treatment and 35 patients, voglibose treatment. The flow-mediated dilatation (FMD) of the brachial artery was measured in the fasting state at baseline and after 12 weeks of treatment. The primary endpoint was a change in FMD (ΔFMD) from the baseline to the end of follow-up. The effects of sitagliptin and voglibose on FMD were assessed by ANCOVA after adjustment for the baseline FMD, age, sex, current smoking, diabetes duration and body mass index. Secondary efficacy measures included changes in HbA1c, GIP, GLP-1, C-peptide, CD34, lipid profile, oxidative stress markers, inflammatory markers and eGFR and any adverse events. RESULTS: ΔFMD was significantly improved after 12 weeks of treatment in both groups, and there was no significant difference in ΔFMD between the two groups. There were no significant differences in changes in HbA1c, GIP, GLP-1, C-peptide, lipid profile, oxidative stress marker, inflammatory marker and eGFR between the two groups. Compared with voglibose, sitagliptin significantly increased the circulating CD34, a marker of endothelial progenitor cells. Adverse events were observed in 5 patients in only the voglibose group (diarrhea 1, nausea 1, edema 2 and abdominal fullness 1). CONCLUSIONS: Sitagliptin improved endothelial dysfunction just as well as voglibose in patients with type 2 diabetes. Sitagliptin had protective effects on endothelial function without adverse events. TRIAL REGISTRATION: registered at http://www.umin.ac.jp/ctrj/ under UMIN000003951.

Serum n-3 to n-6 polyunsaturated fatty acids ratio correlates with coronary plaque vulnerability: an optical coherence tomography study.

A low ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) has been demonstrated to be associated with a higher risk of cardiovascular events. Optical coherence tomography (OCT) is useful for the assessment of coronary plaque vulnerability. The purpose of this study was to evaluate the association between EPA/AA ratio and coronary plaque vulnerability. This study involved 58 patients with stable angina pectoris undergoing percutaneous coronary intervention. OCT image acquisition was performed before the procedure in the culprit lesions. We assessed lipid-rich plaque length and arc, fibrous cap thickness, frequency of thin-cap fibroatheroma (TCFA), thrombus, ruptured plaque, macrophage infiltration, and microvessels using OCT. Patients were divided into two groups according to the median value of serum EPA/AA ratio: a low-EPA/AA group (n = 29, EPA/AA ratio <0.36) and a high-EPA/AA group (n = 29, EPA/AA ratio ≥0.36). In qualitative analyses, TCFA (35.4 vs 6.9 %, P = 0.0095), macrophage infiltration (48.3 vs 13.8 %, P = 0.0045), and microvessels (44.8 vs 10.3 %, P = 0.0033) were more frequently observed in the low-EPA/AA group. In quantitative analyses, the low-EPA/AA group had wider maximum lipid arc (114.0 ± 94.8° vs 56.4 ± 66.0°, P = 0.0097), longer lipid length (4.8 ± 4.5 vs 1.6 ± 2.6 mm, P = 0.0037), and thinner fibrous cap (69.3 ± 28.3 vs 113.3 ± 46.6 µm, P = 0.005) compared with the high-EPA/AA group. EPA/AA ratio was positively correlated with fibrous cap thickness (r = 0.46, P = 0.007). In a multivariate model, an EPA/AA ratio <0.36 was associated with the presence of TCFA (odds ratio 6.41, 95 % confidence interval 1.11-61.91, P = 0.0371). In our detailed OCT analysis, lower EPA/AA ratio was associated with higher vulnerability of coronary plaques to rupture.