Kenta Ito

Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo

BACKGROUNDnThe importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined.nnnMETHODS AND RESULTSnEach animal received a sirolimus-eluting stent (SES) and a biolimus A9-eluting stent (BES), one in the left anterior descending and another in the left circumflex coronary arteries in a randomized manner (n=18). After 1, 3 and 6 months, coronary vasomotion was examined. At 1 month, coronary vasoconstriction to serotonin was significantly enhanced at the SES edges as compared with the BES edges (SES, 52±7% vs. BES, 22±3%, P<0.01), which was equally prevented by a selective Rho-kinase inhibitor, hydroxyfasudil. A significant difference in vasoconstriction between SES and BES was sustained for 6 months. A micro-CT showed VV augmentation at the SES site, extending to the proximal and distal edges. Immunostainings demonstrated that VV formation, macrophage infiltration in the adventitia and Rho-kinase expressions/activation were significantly enhanced at the SES edges as compared with the BES edges.nnnCONCLUSIONSnThe DES with durable polymers enhances VV formation and inflammation in the adventitia, associating with the pathogenesis of DES-induced coronary hyperconstriction through Rho-kinase activation in pigs in vivo.

Increased Coronary Perivascular Adipose Tissue Volume in Patients With Vasospastic Angina

BACKGROUNDnRecent studies have suggested that coronary perivascular adipose tissue (PVAT) impairs coronary vasomotion, so we examined whether PVAT is increased at the spastic coronary segment in patients with vasospastic angina (VSA).nnnMETHODSANDRESULTSnPVAT volume in the left anterior descending (LAD) coronary arteries on CT coronary angiography was significantly increased in 48 VSA patients with LAD spasm compared with 18 controls (30.7±2.0 vs. 21.0±3.2 cm(3), P=0.01), whereas that of total epicardial adipose tissue was comparable between the 2 groups.nnnCONCLUSIONSnThe results suggested an important role of PVAT in the pathogenesis of coronary spasm. (Circ J 2016; 80: 1653-1656).

Enhanced Adventitial Vasa Vasorum Formation in Patients With Vasospastic Angina: Assessment With OFDI.

Coronary artery spasm plays important roles in the pathogenesis of a wide range of ischemic heart disease. Recent studies have demonstrated that coronary spasm is frequently noted in Caucasians as in Asians [(1)][1]. We previously demonstrated that vascular smooth muscle cell hypercontraction

Accuracy of Optical Frequency Domain Imaging for Evaluation of Coronary Adventitial Vasa Vasorum Formation After Stent Implantation in Pigs and Humans – A Validation Study –

BACKGROUNDnCoronary adventitia harbors a wide variety of components, such as inflammatory cells and vasa vasorum (VV). Adventitial VV initiates the development of coronary artery diseases as an outside-in supply route of inflammation. We have recently demonstrated that drug-eluting stent implantation causes the enhancement of VV formation, with extending to the stent edges in the porcine coronary arteries, and also that optical frequency domain imaging (OFDI) is capable of visualizing VV in humans in vivo. However, it remains to be fully validated whether OFDI enables the precise measurement of VV formation in pigs and humans.nnnMETHODS AND RESULTSnIn the pig protocol, a total of 6 bare-metal stents and 12 drug-eluting stents were implanted into the coronary arteries, and at 1 month, the stented coronary arteries were imaged by OFDI ex vivo. OFDI data including the measurement of VV area at the stent edge portions were compared with histological data. There was a significant positive correlation between VV area on OFDI and that on histology (R=0.91, P<0.01). In the human protocol, OFDI enabled the measurement of the VV area at the stent edges after coronary stent implantation in vivo.nnnCONCLUSIONSnThese results provide the first direct evidence that OFDI enables the precise measurement of the VV area in coronary arteries after stent implantation in pigs and humans.

Plasma concentration of serotonin is a novel biomarker for coronary microvascular dysfunction in patients with suspected angina and unobstructive coronary arteries

Aims Although the importance of coronary microvascular dysfunction (CMD) has been emerging, reliable biomarkers for CMD remain to be developed. We examined the potential usefulness of plasma concentration of serotonin to diagnose CMD in patients with suspected angina and unobstructive coronary arteries. Methods and results We enrolled 198 consecutive patients (M/F 116/82, 60.2u2009±u200913.3 years old) who underwent acetylcholine provocation test and measured plasma serotonin concentration. Coronary microvascular dysfunction was defined as myocardial lactate production without or prior to the occurrence of epicardial coronary spasm during acetylcholine provocation test. Although no statistical difference in plasma concentration of serotonin [median (inter-quartile range) nmol/L] was noted between the vasospastic angina (VSA) and non-VSA groups [6.8 (3.8, 10.9) vs. 5.1 (3.7, 8.4), Pu2009=u20090.135], it was significantly higher in patients with CMD compared with those without it [7.7 (4.5, 14.2) vs. 5.6 (3.7, 9.3), Pu2009=u20090.008]. Among the four groups classified according to the presence or absence of VSA and CMD, serotonin concentration was highest in the VSA with CMD group. Importantly, there was a positive correlation between plasma serotonin concentration and baseline thrombolysis in myocardial infarction frame count (Pu2009=u20090.001), a marker of coronary vascular resistance. The classification and regression trees analysis showed that plasma serotonin concentration of 9.55u2009nmol/L was the first discriminator to stratify the risk for the presence of CMD. In multivariable analysis, serotonin concentration greater than the cut-off value had the largest odds ratio in the prediction of CMD [odds ratio (95% confidence interval) 2.63 (1.28–5.49), Pu2009=u20090.009]. Conclusions Plasma concentration of serotonin may be a novel biomarker for CMD in patients with angina and unobstructive coronary arteries.

Focal Vasa Vasorum Formation in Patients With Focal Coronary Vasospasm – An Optical Frequency Domain Imaging Study –

Coronary adventitia has attracted much attention as a source of inflammation because it harbors nutrient blood vessels, oronary artery spasm plays important roles in the pathogenesis of a wide range of ischemic heart disease, not only in vasospastic angina (VSA) but also in other forms of ischemic heart disease.1 Although VSA is believed to be more prevalent in Asian compared with Caucasian subjects,2 it has been recently suggested that the prevalence of VSA could be similar in both populations.3 Thus, coronary spasm is an emerging issue in the world. Furthermore, given C

Usefulness of Testing for Coronary Artery Spasm and Programmed Ventricular Stimulation in Survivors of Out-of-Hospital Cardiac Arrest

Background—Optimal therapy for patients resuscitated from out-of-hospital cardiac arrest (OHCA) who are not found to have structural heart disease remains to be established, especially regarding the use of implantable cardioverter-defibrillators. Coronary artery spasm (CAS) and lethal ventricular arrhythmias are important causes of OHCA. Methods and Results—In 47 consecutive OHCA survivors without structural heart disease who had fully recovered (M/F 44/3, 43±13 years.), we performed dual induction tests, including acetylcholine provocation test first followed by programmed ventricular stimulation after 1 to 2 weeks. Patients with CAS were treated with calcium channel blocker–based antianginal medications; implantable cardioverter-defibrillators were implanted in all patients. The results of the dual induction tests defined 4 groups: CAS alone (n=7), inducible ventricular arrhythmias alone (n=13), both positive (n=24), and both negative (n=3). During a median follow-up period of 38 months, ventricular fibrillation recurred in all groups except the both-negative group. Of the 16 patients with a type I Brugada ECG, 2 had CAS alone, 8 had ventricular arrhythmias alone, and 6 had both positive. No ventricular fibrillation episodes were observed in the CAS-alone patients who did not also have Brugada syndrome. Kaplan–Meier analysis showed that the CAS-alone group was at lower risk for OHCA recurrence as compared with the Brugada syndrome group (log-rank test; P=0.036). Conclusions—Among OHCA survivors without structural heart disease, provokable CAS and ventricular arrhythmias are common and can be seen in Brugada syndrome. CAS alone without Brugada syndrome who are treated for CAS may be a lower-risk group.

Absence of adventitial vasa vasorum formation at the coronary segment with myocardial bridge - An optical coherence tomography study

BACKGROUNDnMyocardial bridge (MB) is a myocardial bundle through which coronary segment tunnels and could compress coronary arteries causing myocardial ischemia. However, the characteristic structural findings of MB remain to be fully elucidated. Recently, we demonstrated that optical coherence tomography (OCT) enables us to visualize adventitial vasa vasorum (VV) formation in humans. In this study, we examined adventitial VV formation at the coronary segment with MB in humans using OCT.nnnMETHODSnWe examined 15 consecutive patients with suspected angina pectoris and MB in the left anterior descending (LAD) coronary arteries but no angiographic coronary stenosis. MB was detected on coronary angiography as a segment with milking effect. We performed intracoronary OCT imaging along the entire LAD. Morphometric analysis was performed at MB and proximal/distal segments at every 1mm.nnnRESULTSnOCT examination showed the absence of adventitial VV formation at MB in the LAD, while VV was clearly noted at both the proximal and distal reference segments. Adventitial VV area was significantly less at MB compared with the proximal or distal references.nnnCONCLUSIONSnThese results with OCT imaging indicate that coronary segments with MB lack adventitial VV formation in humans, suggesting that MB could influence morphological and functional changes of the coronary artery.