Cardiac rupture during the course of treatment for acute purulent pericarditis caused by Staphylococcus aureus: a case report.

Background: Purulent pericarditis is rare in the modern era of antibiotics. However, it is a rapidly progressive, life-threatening disease with complications, including cardiac tamponade and left ventricular pseudoaneurysm. Case summary: A 44-year-old female was admitted with a pontine haemorrhage. On the 25th day of admission, she developed a fever along with chest pain and dyspnoea. Transthoracic echocardiography and computed tomography revealed a large pericardial effusion, leading to the diagnosis of cardiac tamponade. Pericardiocentesis was performed, resulting in the drainage of 750 mL of blood-stained fluid. Blood and pericardial fluid cultures were positive for Staphylococcus aureus; therefore, ceftriaxone was administered. On the 49th day, she became febrile again, and computed tomography showed increased pericardial effusion. Transthoracic echocardiography confirmed the large pericardial effusion and revealed a pseudoaneurysm on the inferior of the left ventricular wall, with blood flowing from the pseudoaneurysm into the pericardial space. Urgent surgical intervention was performed to repair a myocardial defect as a left ventricular pseudoaneurysm had ruptured in the pericardium. The patient recovered and was transferred to another hospital for rehabilitation after 108 days of hospitalization. Discussion: Purulent pericarditis can be a lethal complication; therefore, careful follow-up and strict adherence to therapeutic strategies, including the use of imaging technologies such as echocardiography, are important.

Coronary air embolism during transcatheter patent foramen ovale closure for platypnea-orthodeoxia syndrome in a patient with severe respiratory disorder: a case report.

Background: Coronary air embolism (CAE) is a rare and life-threatening complication of endovascular procedures, mostly due to procedure-related causes. Case summary: A 70-year-old man with severe respiratory disorder presented with patent foramen ovale (PFO)-related platypnea-orthodeoxia syndrome (POS). Transcatheter PFO closure was performed under local anaesthesia and intracardiac echocardiographic guidance. After a 5-Fr catheter was passed through the PFO via a 7-Fr femoral vein sheath, the patient suddenly coughed and breathed deeply. Thereafter, intracardiac echocardiography showed massive microbubbles in all cardiac chambers and the ascending aorta, and an electrocardiogram showed ST-segment elevations in the anterior and inferior leads. Emergency coronary angiography confirmed occlusion of the mid-left anterior descending artery, suggesting CAE. As the intracoronary infusion of saline, nitroglycerine, and nicorandil was ineffective, we performed air aspiration using a thrombectomy device, achieving coronary blood flow improvement and ST-segment resolution. Thereafter, positive pressure support using manual bag-valve-mask ventilation under intravenous sedation supported successful transcatheter PFO closure without further air embolization. Discussion: In this case with severe respiratory dysfunction, spontaneous deep breathing (spontaneous Valsalva manoeuvre) caused negative intrathoracic pressure and large drops in intravascular pressure. This phenomenon might have induced air contamination during device advancement, either by entrapping or leaving residual air in the gaps between the catheter and the sheath. Additionally, PFO with right-to-left shunts is more likely to cause paradoxical air embolization. Thus, the spontaneous Valsalva manoeuvre should be avoided with appropriate respiratory management to prevent paradoxical air embolization, including CAE, during transcatheter PFO closure under local anaesthesia in severe respiratory dysfunction patients.

Prediction of the debulking effect of rotational atherectomy using optical frequency domain imaging: a prospective study.

This study determined the predictive accuracy of optical frequency domain imaging (OFDI) on debulking effects of rotational atherectomy (RA) and compared the predictive accuracy of OFDI catheter-based with Rota wire-based prediction methods. This prospective, single-center, observational study included 55 consecutive patients who underwent OFDI-guided RA. On pre-RA OFDI images, a circle, identical to the Rota burr was drawn at the center of the OFDI catheter (OFDI catheter-based prediction method) or wire (wire-based prediction method). The area overlapping the vessel wall was defined as the predicted ablation area (P-area). The actual ablated area (A-area) was measured by superimposing the OFDI images before and after RA. The overlapping P-area and A-area were defined as overlapped ablation area (O-area), and the predictive accuracy was evaluated by %Correct area (O-area/P-area) and %Error area (A-area - O-area/A-area). The median %Correct and %Error areas were 47.8% and 41.6%, respectively. Irrelevant ablation (low %Correct-/high % Error areas) and over ablation (high %Correct-/high % Error areas) were related to deep vessel injury and intimal flap outside the P-area. The predictive accuracy was better in the OFDI catheter-based prediction method than the wire-based prediction method in the cross sections where the OFDI catheter and wire came in contact. However, it was better in the latter than the former where the OFDI catheter and wire were not in contact. OFDI-based simulation of the RA effect is feasible though accuracy may be affected by the OFDI catheter and wire position. OFDI-based simulation of RA effect might reduce peri-procedural complications during RA.

Optical Coherence Tomography Fractional Flow Reserve and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome.

BACKGROUND: Optical coherence tomography-derived fractional flow reserve (OCT-FFR) correlates strongly with wire-based FFR; however, its clinical significance remains uncertain. OBJECTIVES: This study sought to investigate the relationship between post-percutaneous coronary intervention (PCI) OCT-FFR and long-term clinical outcomes in acute coronary syndrome (ACS). METHODS: This retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent OCT-guided emergency PCI. We analyzed post-PCI OCT images and calculated OCT-FFR to identify independent factors associated with target vessel failure (TVF) after PCI. RESULTS: Among 364 enrolled patients, 54 experienced TVF during a median follow-up of 36 (IQR: 26-48) months. Vessel-level OCT-FFR was significantly lower in the TVF group than in the non-TVF group (0.87 vs 0.94; P < 0.001). In the multivariable Cox regression analysis, low vessel-level OCT-FFR (HR per 0.1 increase: 0.38; 95% CI: 0.29-0.49; P < 0.001) and thin-cap fibroatheroma in the nonculprit lesion were independently associated with TVF. The TVF rate of vessels with both low vessel-level OCT-FFR (<0.90) and thin-cap fibroatheroma in the nonculprit lesion was 8.1 times higher than that of all other vessels (69.3% vs 12.4%; HR: 8.13; 95% CI: 4.33-15.25; log-rank P < 0.001). Furthermore, adding vessel-level OCT-FFR to baseline characteristics and post-PCI OCT findings improved discriminatory and reclassification ability in identifying patients with subsequent TVF. CONCLUSIONS: Vessel-level OCT-FFR was an independent factor associated with TVF after PCI in patients with ACS. Adding the OCT-FFR measurement to post-PCI OCT findings may enable better discrimination of patients with subsequent TVF after PCI for ACS. (Relationship between Intracoronary Optical Coherence Tomography Derived Virtual Fractional Flow Reserve and cardiovascular outcome on Acute coronary syndrome; UMIN000043858).

Kounis syndrome leading to triple-vessel coronary artery ischaemia due to simultaneous coronary spasm, plaque erosion, and multiple stent thrombosis: a case report.

Background: Kounis syndrome (KS) is an acute coronary syndrome (ACS) induced by allergic reactions. Currently, there are three variants of KS based on the mechanism and onset of ACS. We report a rare case of KS, wherein ACS was caused by all KS variants. Case summary: A 68-year-old man with a history of percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction of the left anterior descending artery 16 days ago underwent a staged PCI for the mid-left circumflex artery (LCx) stenosis under optical coherence tomography (OCT) guidance using low-molecular-weight dextran (LMWD). During OCT examination, the LMWD induced an anaphylactic reaction. The patient was immediately administered medications to manage the anaphylaxis; however, he complained of chest discomfort. Coronary angiography and subsequent intravascular ultrasound revealed a newly developed coronary thrombus in the proximal LCx. Furthermore, coronary spasm or multiple stent thromboses occurred sequentially in all coronary arteries, resulting in triple-vessel coronary artery ischaemia. Balloon angioplasty was performed under intra-aortic balloon pumping, which could rescue the patient. The patient was discharged without any complications 11 days post-KS, under a 7-day anti-histamine regimen. No further cardiovascular events had occurred by 1-year follow-up. Discussion: This case documented the clinical course of KS caused by LMWD, wherein all KS variants occurred sequentially. Early recognition of KS and appropriate management with anaphylaxis medication and balloon angioplasty under mechanical circulatory support effectively prevent vascular morbidity. Interventionalists should be aware of this rare and serious complication of PCI.

Cholesterol uptake capacity: A new measure of high-density lipoprotein functionality as a predictor of subsequent revascularization in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: High-density lipoprotein (HDL) functionality is an important determinant of coronary artery disease (CAD) development. We recently developed cholesterol-uptake capacity (CUC), a rapid cell-free assay system that directly evaluates the capacity of HDL to accept additional cholesterol. We aimed to evaluate the association between CUC and revascularization in patients who have undergone percutaneous coronary intervention (PCI). METHODS: We retrospectively reviewed patients who underwent PCI with subsequent revascularization or coronary angiography (CAG) without revascularization. The patients who had frozen blood samples for which CUC were measurable at the index PCI and follow-up were enrolled. RESULTS: We finally enrolled 74 patients who underwent subsequent revascularization and 183 patients who underwent follow-up CAG without revascularization. The serum CUC level at the index PCI was significantly lower in the revascularization group than that in the non-revascularization group (84.3 [75.2-98.9] vs. 92.0 [81.6-103.3 A U.]; p = 0.004). Multivariate logistic regression analysis revealed that decreased serum CUC level at the index PCI was independently associated with subsequent revascularization (odds ratio, 0.98; 95% confidence interval, 0.969-1.000). After adjusting for 16 cardiovascular risk factors, the serum CUC level at the index PCI and follow-up and the absolute change in serum CUC level from the index PCI to follow-up were significantly lower in the revascularization group than those in the non-revascularization group. CONCLUSIONS: Serum CUC level at index PCI was independently associated with subsequent revascularization after PCI. Continuous assessment of HDL functionality by CUC might help predict subsequent revascularization after PCI.

Progression from normal vessel wall to atherosclerotic plaque: lessons from an optical coherence tomography study with follow-up of over 5 years.

The initial process of atherosclerotic development has not been systematically evaluated. This study aimed to observe atherosclerotic progression from normal vessel wall (NVW) to atherosclerotic plaque and examine local factors associated with such progression using > 5-year long-term follow-up data obtained by serial optical coherence tomography (OCT). A total of 49 patients who underwent serial OCT for lesions with NVW over 5 years (average: 6.9 years) were enrolled. NVW was defined as a vessel wall with an OCT-detectable three-layer structure and intimal thickness ≤ 300 µm. Baseline and follow-up OCT images were matched, and OCT cross sections with NVW > 30° were enrolled. Cross sections were diagnosed as "progression" when the NVW in these cross sections was reduced by > 30° at > 5-year follow-up. Atherogenic progression from NVW to atherosclerotic plaque was observed in 40.8% of enrolled cross sections. The incidence of microchannels in an adjacent atherosclerotic plaque within the same cross section (6.7 vs. 3.3%; p = 0.046) and eccentric distribution of atherosclerotic plaque (25.0 vs. 12.6%; p < 0.001) at baseline was significantly higher in cross sections with progression than in those without. Cross sections with progression exhibited significantly higher NVW intimal thickness at baseline than cross sections without progression (200.1 ± 53.7 vs. 180.2 ± 59.6 µm; p < 0.001). Multivariate analysis revealed that the presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness at baseline were independently associated with progression at follow-up. The presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness were potentially associated with initial atherosclerotic development from NVW to atherosclerotic plaque.

Association Between Visit-to-Visit Variability in Low-Density Lipoprotein Cholesterol and Plaque Rupture That Leads to Acute Coronary Syndrome.

Background: The effect of intraindividual variability in lipid levels on the onset of acute coronary syndrome (ACS) remains uncertain. We evaluated the relationship between intraindividual variability in lipid levels and culprit lesion morphologies by optical coherence tomography (OCT). Methods and Results: Seventy-four consecutive patients with ACS whose cholesterol levels were assessed ≥3 times during outpatient visits before the onset of ACS were enrolled in the study; 222 patients without significant stenotic lesions were used as a control group. Based on OCT findings of culprit lesions, ACS patients were categorized into a plaque rupture ACS (PR-ACS) group (n=44) or a non-plaque rupture ACS (NPR-ACS) group (erosion or calcified nodule; n=30). Visit-to-visit variability in lipid levels was evaluated using the corrected variability independent of the mean (cVIM). Patients with ACS had significantly higher low-density lipoprotein cholesterol (LDL-C) levels and cVIM in LDL-C than the control group. The PR-ACS group had significantly higher mean LDL-C levels and greater cVIM in LDL-C than the control group. The PR-ACS group had a significantly higher cVIM than the NPR-ACS group, despite similar mean LDL-C levels. Multivariate analysis revealed that higher cVIM of LDL-C was an independent predictor of PR-ACS (odds ratio 1.06; P=0.018). Conclusions: In addition to the LDL-C level, greater visit-to-visit variability in LDL-C levels may be associated with the onset of ACS induced by plaque rupture.

Morphological Plaque Characteristics and Clinical Outcomes in Patients With Acute Coronary Syndrome and a Cancer History.

Background Although patients with a cancer history have a 2 to 3 times higher risk for acute coronary syndrome (ACS), the morphological characteristics of ACS culprit plaque in those patients and their relations with clinical outcomes remain unknown. Methods and Results This retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent optical coherence tomography-guided emergent percutaneous coronary intervention. Patients were categorized into those without a cancer history, those with a cancer history, and those currently receiving cancer treatment. ACS culprit lesions were classified as plaque rupture, plaque erosion, or calcified nodule using optical coherence tomography. Plaque erosion frequency was significantly higher in culprit lesions of patients with current cancer and patients with cancer history than in those of patients without cancer history (56.3% versus 61.7% versus 36.5%). Calcified nodule incidence was significantly higher in patients without cancer history than in patients with current cancer and patients without cancer history (patients with current cancer: 12.4% versus patients without cancer history: 25.5% versus patients without cancer history: 12.6%, P<0.001). Cancer history was independently associated with nonplaque rupture (plaque erosion or calcified nodule) in ACS culprit lesions (odds ratio, 4.00; P<0.001). Cancer history was independently associated with major adverse cardiovascular events (hazard ratio [HR], 1.98; P=0.002). Nonplaque rupture in ACS culprit lesions was independently associated with major adverse cardiovascular events (HR, 1.60; P=0.011). Conclusions Patients with a cancer history had significantly worse clinical outcomes after ACS than those without a cancer history. Those with a cancer history had significantly higher plaque erosion and calcified nodule incidences in the ACS culprit lesions, which might partly explain their worse clinical outcomes. Registration URL: www.umin.ac.jp/ctr/index.htm. Unique Identifier: UMIN000038442.

Relationship among clinical characteristics, morphological culprit plaque features, and long-term prognosis in patients with acute coronary syndrome.

Culprit lesions of acute coronary syndrome (ACS) could be classified as plaque rupture (PR), erosion, or calcified nodule (CN). We aimed to determine the relationship among clinical characteristics, morphological plaque features, and long-term prognosis in ACS. Patients with ACS, who underwent pre-intervention optical coherence tomography between April 2013 and July 2018 were retrospectively enrolled, and classified into the three groups based on the culprit lesion morphology. In the 436 patients enrolled, incidences of PR, erosion, and CN in ACS culprit lesions were 46.1, 39.9, and 14.0%, respectively. Plaque erosion was more frequent in men aged < 60 years and CN was more frequent in older adults in both sexes (≥ 80 years) (P < 0.001). Patients with CN had a higher incidence of hemodialysis treatment (P < 0.001) and diabetes (P = 0.003). Multivariate analysis revealed that ST elevation myocardial infarction (STEMI) (P = 0.049) and presence of thin-cap fibroatheroma (TCFA) at the culprit lesion were independently associated with PR; in younger patients (< 60 year), preserved left ventricular ejection fraction and lower incidence of TCFA were correlated with plaque erosion; and older age, non-STEMI, or unstable angina pectoris, higher serum brain natriuretic peptide levels, and lower incidence of TCFA were independently associated with CN. Multivariable analysis revealed that CN (odds ratio [OR] 1.990, P = 0.005), male sex (OR 2.012, P = 0.004), and older age (OR 1.036, P < 0.001) were independently associated with future adverse events during a median follow-up of 757 days. Different patient characteristics and morphological features were associated with the type of culprit lesion in patients with ACS.

Prediction of the debulking effect of rotational atherectomy using optical frequency domain imaging.

Whether predicting the rotational atherectomy (RA) effect based on the position of optical frequency domain imaging (OFDI) is accurate remains uncertain. The aim of this study was to evaluate the predictive accuracy of OFDI in identifying RA location and area. Twenty-five patients who underwent RA with OFDI were included. On pre-RA OFDI images, a circle with the dimension of a Rota burr was drawn at the center of the OFDI catheter. The area where the circle overlapped with the vessel wall was defined as the predicted ablation area (P-area), and the actual ablated area (A-area) was measured. The predictive accuracy of OFDI was evaluated as follows: overlapped ablation area (O-area: overlapping P- and A-areas) divided by P-area = %Correct-area, and A-area - O-area divided by A-area = %Error-area. Cross-sections were separated into four categories based on the median values of %Correct- and %Error-area. Among 334 cross-sections, RA effects were confirmed in the predicted location in 87% of them. The median %Correct- and %Error-areas were 43.1% and 64.2%, respectively. Floppy wire, narrow lumen area, OFDI catheter close to the intima, and large arc of calcium were independently associated with good prediction (high %Correct-/low %Error-areas). Non-left anterior descending lesions, OFDI catheter far from the wire, and OFDI catheter and wire far from the intima were associated with irrelevant ablation (low %Correct-/ high %Error-areas). The accuracy of the OFDI-based predictions for RA effects was acceptable with regard to location, but not high with regard to area. Wire types, target vessels, and OFDI catheter and wire positions are important determinants for accurately predicting RA effect using pre-procedural OFDI.

Efficacy of optical frequency domain imaging in detecting peripheral artery disease: the result of a multi-center, open-label, single-arm study.

Optical frequency domain imaging (OFDI) is a high-resolution intracoronary imaging modality with fast automated longitudinal pullback. We aimed to evaluate the ability of performing OFDI from the superficial femoral artery (SFA) to the below-knee (BK) artery. This clinical trial was a multi-center, single-arm, open-label study. The primary endpoint was to obtain a clear image of the intra-vascular lumen from the SFA to the BK artery, specifically > 270° visualization of the blood vessel lumen with > 16/21 cross sections. The proportion of the clear image (≥ 85%) was regarded as confirmatory of the ability of OFDI to visualize the vessel lumen. Overall, 20 patients were enrolled. The proportion of the primary endpoint was 90% (18/20), and the pre-specified criterion was successfully attained. The proportion of the clear image assessed by the operator was 100% (20/20), and an additional statistical analysis for the proportion of the visualization, > 270°, of the blood vessel lumen revealed a significantly higher cut-off value than that for the pre-specified criterion, 85% (p = 0.0315). There were three adverse events not related to OFDI. OFDI achieved acceptable visualization of the vessel lumen without any adverse event related to it. After regulatory approval based on the present study, OFDI will be available as a new option of endovascular imaging for peripheral artery diseases in daily practiceTrial registration: This study was registered in the Japanese Registry of Clinical Trials (jRCT 2052190025, https://jrct.niph.go.jp/latest-detail/jRCT2052190025 ).

Feasibility of morphological assessment of coronary artery calcification with electrocardiography-gated non-contrast computed tomography: a comparative study with optical coherence tomography.

To investigate the feasibility of pre-procedural morphological assessment of coronary artery calcification in severely calcified lesions with electrocardiography (ECG)-gated non-contrast computed tomography (CT). Severely calcified coronary arteries in patients who underwent ECG-gated non-contrast CT prior to optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) were studied retrospectively. CT and OCT data were co-registered by marking landmark structures such as side branches and reviewed side by side with cross-sectional images. The maximum calcium angle (MCA) and presence of nodular calcification (NC) were evaluated. A total of 496 cross-sections in 16 lesions were included in this analysis. The Pearson correlation coefficient between CT- and OCT-derived MCA was 0.92 (p < 0.001). Bland-Altman plots of OCT-derived MCA in relation to CT-derived MCA showed a mean bias of 4.8 degrees with 95% limits of agreement of - 69.7 to 79.4 degrees. Sensitivity, specificity, and positive and negative predictive values of CT in identifying MCA > 270 degrees were 90.3%, 79.7%, 92.1%, and 97.4%, respectively. Sensitivity, specificity, and positive and negative predictive values of CT in identifying NC were 73.3%, 97.5%, 47.8%, and 99.2%, respectively. ECG-gated non-contrast coronary CT might be helpful to obtain detailed information of severe coronary artery calcification before PCI.

Concomitant Use of Rosuvastatin and Eicosapentaenoic Acid Significantly Prevents Native Coronary Atherosclerotic Progression in Patients With In-Stent Neoatherosclerosis.

BACKGROUND: In-stent neoatherosclerosis (NA) is a risk for future cardiovascular events through atherosclerotic progression in non-stented lesions. Using optical coherence tomography, this study assessed the efficacy of intensive therapy with 10 mg/day rosuvastatin plus 1,800 mg/day eicosapentaenoic acid (EPA) vs. standard 2.5 mg/day rosuvastatin therapy on native coronary plaques in patients with NA.Methods and Results:This was a subgroup analysis of the randomized LINK-IT trial, which was designed to compare changes in the lipid index in NA between intensive and standard therapy for 12 months. In all, 42 patients with native coronary plaques and NA were assessed. Compared with standard therapy, intensive therapy resulted in greater decreases in serum low-density lipoprotein cholesterol concentrations and greater increases in serum 18-hydroxyeicosapentaenoic acid concentrations, with significantly greater decreases in the lipid index and macrophage grade in both NA (-24 vs. 217 [P<0.001] and -15 vs. 24 [P<0.001], respectively) and native coronary plaques (-112 vs. 29 [P<0.001] and -17 vs. 1 [P<0.001], respectively) following intensive therapy. Although there was a greater increase in the macrophage grade in NA than in native coronary plaques in the standard therapy group, in the intensive therapy group there were comparable reductions in macrophage grade between NA and native coronary plaques. CONCLUSIONS: Compared with standard therapy, intensive therapy prevented atherosclerotic progression more effectively in native coronary plaques in patients with NA.

Correction to: Efficacy of optical frequency­domain imaging in detecting peripheral artery disease: a single­center open­label, single­arm study protocol.

In the original publication of the article, the author group was published without full names and one of the co-authors' name was published incorrectly. The full names of author group and correct co-authors' name are given in this Correction.

Efficacy of optical frequency-domain imaging in detecting peripheral artery disease: a single-center open-label, single-arm study protocol.

Intravascular optical coherence tomography is a high-resolution intracoronary imaging modality, providing a microscopic image of intravascular features. However, it has lower penetration depth than intravascular ultrasound. Recently, a second-generation optical frequency-domain imaging (OFDI) technique has been developed to provide greater penetration depth and faster pullback speed. However, there is little evidence supporting the efficacy of OFDI in patients with peripheral artery disease (PAD) undergoing endovascular treatment (EVT). We aimed to evaluate the ability of OFDI to visualize vessel walls from the superficial femoral artery (SFA) to the below-knee (BK) arteries, as well as the coronary arteries. This clinical trial is a single-center, single-arm, open-label study to be conducted in Japan. A total of 20 patients will be enrolled in this study. The primary endpoint is to obtain a clear image of the intravascular features of the SFA and BK arteries, specifically the visualization of ≥ 270° of the vessel lumen in ≥ 16 out of 21 cross sections. Obtaining clear images in ≥ 85% of cases will be regarded as confirmation of the ability of OFDI to visualize vessel walls from the SFA to the BK arteries. This is the first clinical trial to be conducted accordance with good clinical practice to expand the indications of OFDI for PAD patients undergoing EVT in Japan. The result of this study will help provide another imaging option during EVT in daily practice.

Efficacy of alirocumab for reducing plaque vulnerability: Study protocol for ALTAIR, a randomized controlled trial in Japanese patients with coronary artery disease receiving rosuvastatin.

BACKGROUND: Although a recent clinical trial demonstrated that alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, significantly reduces the incidence of acute coronary events, the impact of alirocumab on plaque stabilization remains uncertain. The Efficacy of ALirocumab for Thin-cap fibroatheroma in patients with coronary Artery disease estImated by optical coherence tomogRaphy (ALTAIR) study will investigate the effect of alirocumab on thin-cap fibroatheroma (TCFA) in Japanese patients who underwent recent percutaneous coronary intervention (PCI). METHODS AND DESIGN: ALTAIR is a phase IV, open-label, randomized, parallel-group, single-center study involving blinded optical coherence tomography (OCT) image analysis in Japanese adults hospitalized for PCI and having suboptimal control of low-density lipoprotein cholesterol (LDL-C) levels (>70mg/dL) despite statin therapy. Patients will be randomized (1:1) to the alirocumab arm (alirocumab 75mg every 2 weeks added to rosuvastatin 10mg/day) or the standard-of-care arm (rosuvastatin 10mg/day, with initiation and/or dose adjustment of non-statin lipid-lowering to achieve an LDL-C target of <70mg/dL). OCT imaging will be conducted at baseline and at week 36 (post-treatment). The primary objective is to compare the alirocumab and standard-of-care arms regarding the change in TCFA fibrous-cap thickness after 9 months of treatment. CONCLUSION: The outcomes of ALTAIR (ClinicalTrials.gov identifier: NCT03552432) will provide insights into the effect of alirocumab on plaque vulnerability following PCI in patients with suboptimal LDL-C control despite stable statin therapy.

Effect of Alirocumab and Rosuvastatin or Rosuvastatin Alone on Lipid Core Plaque in Coronary Artery Disease Seen on Near-Infrared Spectroscopy Intravascular Ultrasound (ANTARES).

Background: Despite evidence of the effects of alirocumab on the incidence of acute coronary events, its impact on plaque stabilization remains uncertain. The present study will investigate the effect of alirocumab on fibroatheroma in patients who underwent recent percutaneous coronary intervention (PCI). Methods and Results: This phase IV, open-label, randomized, blinded near-infrared spectroscopy plus intravascular ultrasound (NIRS-IVUS) analysis, parallel-group, single-center study will enroll Japanese adults recently hospitalized for PCI with suboptimal low-density lipoprotein cholesterol (LDL-C) control (>70 mg/dL) despite stable statin therapy. Thirty patients will be randomized to receive either alirocumab or standard of care. The alirocumab group will receive alirocumab 75 mg every 2 weeks plus 10 mg rosuvastatin per day. The standard-of-care group will receive 10 mg rosuvastatin per day with dose adjustment to achieve LDL-C <70 mg/dL. Post-treatment NIRS-IVUS will be performed at week 36. The primary endpoint is the change in maximum lipid core burden index in 4-mm pullback compartments (maxLCBI[4 mm]) between baseline and week 36. Secondary endpoints include change in LCBI (lesion), angle of lipid core, plaque burden, and serum lipids and biomarkers related to atherosclerosis and inflammation. Conclusions: The study will clarify the effects of alirocumab on thin-cap fibroatheroma in patients who underwent recent PCI and who have suboptimal LDL-C control with stable statin therapy.

Improvement of ectoine productivity by using sugar transporter-overexpressing Halomonas elongata.

We successfully enhanced the productivity of ectoine with Halomonas elongata by improvement of the transport of sugar. First, we carried out screening for sugar transporters capable of improving glucose and xylose consumption. We found two transporters: b3657 from Escherichia coli, which is capable of improving glucose consumption, and HEO_0208 from H. elongata, which is capable of improving xylose consumption. Using transporter-overexpressing strains, the productivity of ectoine was improved. These results indicate that sugar consumption is important for efficient ectoine production. As result of phenotypic analysis of a HEO_0208 deletion strain, we discovered that HEO_0208 is the major xylose transporter in H. elongata. This is the first report demonstrating improvement of ectoine productivity by enhancing the transport of sugar.