Aim: Wide volume scan (WVS) coronary computed tomography angiography (CCTA) enables aortic arch visualization. This study assessed whether the thoracic aortic plaque burden (TAPB) score can predict ...major cardiovascular adverse events (MACE) in addition to and independently of other obstructive coronary artery disease (CAD) attributes.Methods: This study included patients with suspected CAD who underwent CCTA (n=455). CCTA-WVS was used to assess CAD and the prognostic capacity of TAPB scores. Data analysis included the coronary artery calcification score (CACS), CAD status and extent, and TAPB score, calculated as the sum of plaque thickness and plaque angle at five thoracic aortic segments. The primary endpoint was MACE defined as a composite event comprised of ischemic stroke, acute coronary syndrome, and cardiovascular death. Results: During a mean follow-up period of 2.8±0.9 years, 40 of 455 (8.8%) patients experienced MACE. In the Cox proportional hazards model adjusted for clinical risks (Suita cardiovascular disease risk score), we identified TAPB score (T3) as a predictor of MACE independent of CACS ＞400 (hazards ratio HR, 2.91; 95% confidence interval CI, 1.26–6.72; p=0.012) or obstructive CAD (HR, 2.83; 95% CI, 1.30–6.18; p=0.009). The area under the curve for predicting MACE improved from 0.75 to 0.795 (p value=0.008) when TAPB score was added to CACS ＞400 and obstructive CAD. Conclusions: We found that comprehensive non-invasive evaluation of TAPB and CAD has prognostic value in MACE risk stratification for suspected CAD patients undergoing CCTA.
Objectives The aim of this study was to determine the predictive value of the napkin-ring sign on coronary computed tomography angiography (CTA) for future acute coronary syndrome (ACS) events in ...patients with coronary artery disease. Background Recent studies have reported a close association between the napkin-ring sign on coronary CTA and thin-cap fibroatheroma. Methods The subjects of this prospective study were 895 consecutive patients who underwent coronary CTA examination and were followed for >1 year. The primary endpoint was an ACS event (cardiac death, nonfatal myocardial infarction, or unstable angina pectoris). The coronary CTA analysis included the presence of obstructive plaque, positive remodeling (PR), low-attenuation plaque (LAP), and the napkin-ring sign. The napkin-ring sign was defined by the following criteria: 1) the presence of a ring of high attenuation around certain coronary artery plaques; and 2) attenuation of the ring presenting higher than those of the adjacent plaque and no >130 Hounsfield units. Results Of the 12,727 segments, 1,174 plaques were observed, including plaques with PR in 130 segments (1.0%), LAP in 107 segments (0.8%), and napkin-ring signs in 45 segments (0.4%). Thirty-six of the 45 plaques with napkin-ring signs (80%) overlapped with those showing either PR or LAP. During the follow-up period (2.3 ± 0.8 years), 24 patients (2.6%) experienced ACS events, and plaques developed in 41% with a napkin-ring sign. Segment-based Cox proportional hazards models analysis showed that PR (p < 0.001), LAP (p = 0.007), and the napkin-ring sign (p < 0.0001) were independent predictive factors for future ACS events. Kaplan-Meier analysis demonstrated that plaques with napkin-ring signs showed a higher risk of ACS events compared with those without a napkin-ring sign. Conclusions The present study demonstrated for the first time that the napkin-ring sign demonstrated on coronary CTA was strongly associated with future ACS events, independent of other high-risk coronary CTA features. Detection of the napkin-ring sign could help identify coronary artery disease patients at high risk of future ACS events.
Abstract Background Remote ischemic conditioning (RIC) by repeated treatment of transient limb ischemia is a clinically applicable method for protecting the heart against injury at the time of ...reperfusion. In this study, we investigated the effects of repeated RIC on cardiac dysfunction after myocardial infarction (MI). Methods and results At 4 weeks after MI, rats were separated into the untreated (UT) group or the RIC-treated group. RIC treatment was performed by 5 cycles of 5 min of bilateral hindlimb ischemia and 5 min of reperfusion once a day for 4 weeks. Despite comparable MI size, left ventricular (LV) ejection fraction (LVEF) was significantly improved in the RIC group compared with the UT group. Furthermore, the LVEF in the RIC group was improved, although not significantly, after treatment. RIC treatment also prevented the deterioration of LV diastolic function. MI-induced LV interstitial fibrosis in the boundary region and oxidant stress were significantly attenuated by RIC treatment. MicroRNA-29a (miR-29a), a key regulator of tissue fibrosis, was highly expressed in the exosomes and the marginal area of the RIC group. Even in the differentiated C2C12-derived exosomes, miR-29a expression was significantly increased under hypoxic condition. As well as miR-29a, insulin-like growth factor 1 receptor (IGF-1R) was highly expressed both in the exosomes and remote non-infarcted myocardium of the RIC group. IGF-1R expression was also increased in the C2C12-derived exosomes under hypoxic conditions. Conclusions Repeated RIC reduces adverse LV remodeling and oxidative stress by MI. Exosome-mediated intercellular communication may contribute to the beneficial effect of RIC treatment.
Arterial stiffness is a significant predictor of cardiovascular disease (CVD), the risk of which is modified by medications for atherosclerotic risk factors and life-style changes. Cardio-ankle ...vascular index (CAVI) provides noninvasive, objective information on arterial stiffness, independent of blood pressure. This study aimed to investigate changes in CAVI after management of atherosclerotic risk factors, and the impact of these changes on future CVD outcomes in patients with coronary artery disease (CAD). The study consisted of 211 CAD patients (65 ± 10 years, 118 men) with impaired CAVI. CAVI examination was repeated 6 months later. Impaired CAVI was defined as greater than the mean plus 1 s.d. of the age- and gender-specific normal CAVI values, according to results obtained in 5188 healthy subjects. All patients were followed for > 1 year or until the occurrence of a CVD event. Of the 211 patients, CAVI improved in 106 (50%) patients after 6 months, but remained high in 105 (50%) patients. During follow-up (2.9 ± 1.0 years), CVD events occurred in 28 (13%) patients. Persistently impaired CAVI was an independent predictor of future CVD events (P = 0.01), independent of baseline CAVI. CVD outcomes were worse in patients with persistently impaired CAVI than in those with improved CAVI (P < 0.001). Among patients with a normalized CAVI after treatment (n = 22) only one suffered a CVD event. This study was the first to demonstrate that persistent impairment of arterial stiffness was an independent risk factor of future CVD events. Serial measurements of CAVI provide important prognostic information regarding patients with CAD in clinical practice.
Abstract Background Previous pathohistological studies demonstrated that cholesterol crystals (CCs) are frequently observed in atherosclerotic plaques, and are usually present abundantly in ...vulnerable plaques. However, the role of CCs in plaque destabilization, as well as their origin and composition, is unknown. Optical coherence tomography (OCT) imaging system is a high-resolution imaging device, which allows the in vivo identification of CCs accumulating within atherosclerotic plaques. The aim of this study was to investigate the relationship between the presence of CCs, other plaque morphologies assessed by OCT, and patients’ clinical characteristics including acute coronary syndrome (ACS). Methods and results Preinterventional OCT images of 173 patients with either ACS or stable angina pectoris were studied. Of 173 lesions in the patients, 66 (38%) had CCs within the culprit lesion segment and 107 (62%) had non-CC lesions. Multivariate analysis revealed that low high-density lipoprotein cholesterol levels, diabetes mellitus, the presence of plaque rupture, intimal vasculature, and thrombus were independent factors associated with CCs. Moreover, the frequency of CCs increased in proportion to the accumulation of the number of components of their vulnerable plaque features within the culprit lesion segment. Compared with the plaques without thrombus, CCs were present at shallower locations in those with thrombus. Conclusions This study demonstrates the potential correlation between the clinical metabolic disorder and vulnerable morphological features of culprit lesions to the presence of CCs in patients with stable and unstable coronary syndromes. These observations of CCs by using in vivo plaque imaging could provide incremental value to OCT evaluation of atherosclerotic plaques.
Pirfenidone (5-methyl-1-phenyl-2-(1)H-pyridone) is an effective drug for idiopathic interstitial pneumonia that can prevent and reverse tissue fibrosis in several organs. Therefore, we investigated ...whether pirfenidone has a potential role in preventing angiotensin II (Ang II)-induced cardiac hypertrophy. A cardiac hypertrophic mouse model was created using an Ang II infusion (200 ng kg(-1) min(-1)) in wild-type mice for 2 weeks. Mice were divided into the following three groups: a saline-infused (control) group, an Ang II infusion (vehicle) group and an Ang II infusion+pirfenidone-treated (PFD) group, which received pirfenidone (300 mg kg(-1) per day) by gastric gavage during the Ang II infusion. At 2 weeks, we assessed hemodynamics and cardiac function and investigated tissue fibrosis of the myocardium histologically and genetically. Blood pressure in the vehicle group was significantly increased compared to the control group. Although blood pressure was not different between the vehicle and PFD groups, heart weight was significantly decreased in the PFD group. Echocardiography revealed that left ventricular hypertrophy was significantly increased in the vehicle group vs. the control group. Interestingly, pirfenidone significantly inhibited this effect. Continuous infusion of Ang II increased the perivascular and interstitial tissue fibrosis, and pirfenidone inhibited these fibrotic changes. Pirfenidone also inhibited Ang II-induced hypertrophy. In the vehicle group, the mRNA expressions of atrial natriuretic peptide, brain natriuretic peptide and transforming growth factor-β1 were increased, which was significantly inhibited by pirfenidone. Furthermore, the expression of mineralocorticoid receptors was attenuated by pirfenidone. These results indicate that pirfenidone might be effective as an antifibrotic drug in the treatment of cardiac hypertrophy induced by hypertension.
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 m2who 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 m2) or a non-CKD group (eGFR ≥60 ml/min/1.73 m2). 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. (Circ J 2016; 80: 196–201)
Obesity is related to left ventricular (LV) diastolic dysfunction, although its pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) is an ectopic fat with paracrine effects ...on coronary circulation and myocardium. We hypothesized that left ventricle–specific (periventricular) EAT may deteriorate diastolic function by impairing coronary microcirculation.
In protocol 1, 74 patients without obstructive narrowing of the left anterior descending artery on multidetector computed tomography (MDCT) underwent coronary flow reserve (CFR) examination to evaluate the relationship between EAT and coronary microcirculation. In protocol 2, 372 patients who underwent both MDCT and serial transthoracic Doppler echocardiographic (TTDE) examinations were enrolled to investigate the impact of periventricular EAT on changes in diastolic function. EAT volume was measured by MDCT. CFR and diastolic function were assessed by TTDE. Deterioration of LV diastolic function was defined as a ≥ 20% decrease in early diastolic mitral annular velocity.
CFR was significantly correlated with periventricular EAT volume (r = −0.37; P = 0.001), but not with total EAT volume (r = −0.21; P = 0.071). Periventricular EAT volume (P = 0.010) was significantly associated with CFR independent of cardiovascular risk factors. Among the 372 patients who had serial TTDE examinations, the frequency of deteriorated LV diastolic function was lowest in the lower tertile of periventricular EAT, intermediate in the middle tertile, and highest in the upper tertile (12.9%, 21.0%, and 25.8%, respectively; P = 0.037). Age, diabetes mellitus, and periventricular EAT volume were significantly associated with deterioration of LV diastolic function (all P < 0.05).
This study demonstrated the close association of periventricular EAT with impaired CFR and deteriorated LV diastolic function.
L’obésité est liée à une dysfonction diastolique du ventricule gauche (DDVG), même si l’on méconnaît son mécanisme physiopathologique. Le tissu adipeux épicardique (TAE) est un tissu graisseux ectopique qui a des effets paracrines sur la circulation coronaire et le myocarde. Nous avons postulé que la présence de TAE autour du ventricule gauche (périventriculaire) pouvait détériorer la fonction diastolique en altérant la microcirculation coronaire.
Dans le cadre du protocole 1, 74 patients exempts de sténose obstructive de l’artère descendante antérieure gauche à la tomographie à multidétecteurs (TGMD) ont été soumis à un examen de la réserve coronaire pour évaluer le lien entre le TAE et la microcirculation coronaire. Dans le cadre du protocole 2, 372 patients, ayant subi une TGMD et une échocardiographie doppler transthoracique à balayage séquentiel, ont été inscrits à l’étude pour évaluer les effets du TAE périventriculaire sur les changements de la fonction diastolique. Le volume du TAE a été mesuré par TGMD. La réserve coronaire et la fonction diastolique ont été évaluées par échocardiographie doppler transthoracique. La détérioration de la fonction diastolique du ventricule gauche a été définie comme une diminution de ≥ 20 % de la vélocité annulaire mitrale diastolique précoce.
On a observé une corrélation significative entre la réserve coronaire et le volume du TAE périventriculaire (r = −0,37; p = 0,001), mais aucune corrélation avec le volume total de TAE (r = −0,21; p = 0,071). Le volume du TAE périventriculaire (p = 0,010) a été associé de façon significative à la réserve coronaire sans égard aux facteurs de risque cardiovasculaire. Parmi les 372 patients soumis à des examens périodiques par échocardiographie doppler transthoracique, la fréquence de détérioration de la fonction diastolique du ventricule gauche était la plus faible dans le tertile inférieur du TAE périventriculaire, intermédiaire dans le tertile moyen, et la plus élevée dans le tertile supérieur (12,9 %, 21,0 % et 25,8 %, respectivement; p = 0,037). L’âge, le diabète et le volume du TAE périventriculaire étaient significativement associés à une détérioration de la fonction diastolique du ventricule gauche (p < 0,05 dans tous les cas).
Cette étude a montré l’existence d’un lien étroit entre le TAE périventriculaire et l’altération de la réserve coronaire et la détérioration de la fonction diastolique du ventricule gauche.
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).BackgroundDiabetes 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).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.MethodsWe 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.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.ResultsThe 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.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.ConclusionsThis study demonstrated that DM, rather than MetS, is a predictor of coronary events independent of high-risk plaque volume in patients who underwent CCTA.
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