Rapidly Moving Vanishing Tumor of the Lung After Open-heart Surgery.

Vanishing tumor of the lung, also known as phantom tumor, is uncommonly observed in congestive heart failure. We report a case of a vanishing tumor that rapidly disappeared and reappeared in just a few minutes due to repositioning in a patient after open-heart surgery.

Discontinuation of Intravenous Catecholamine by Oral Ivabradine in a Patient with Decompensated Heart Failure with Low Cardiac Output Syndrome.

Ivabradine has been shown to improve heart failure with sinus tachycardia by reducing the heart rate without affecting left ventricular systolic function or blood pressure. Here we report a case of a catecholaminedependent patient, New York Heart Association (NYHA) class IV, LVEF of 18%, and low cardiac output, who was able to discontinue intravenous catecholamine by oral administration of ivabradine.

Successful introduction of robotic-assisted percutaneous coronary intervention system into Japanese clinical practice: a first-year survey at single center.

In Japan, a robotic-assisted PCI (R-PCI) system, the CorPath GRX System (Corindus Inc.), has been approved for clinical use in 2018, which is the first introduction of R-PCI into Japan. In this study, the clinical performance of the R-PCI system in the initial year at Kurume University Hospital was evaluated comparing with conventional manual PCI (M-PCI). A total of 30 R-PCI and 77 M-PCI procedures performed between April 2019 and March 2020, were retrospectively included. The primary outcome was the rate of clinical success defined as < 30% residual stenosis without in-hospital major adverse cardiovascular events (MACE). The secondary outcomes were fluoroscopy time, dose area product (DAP), amount of radiation exposure to operators and assistants, procedural time, and contrast volume. Propensity-matching technique was used to match each R-PCI lesion to the nearest M-PCI lesion without replacement. After propensity score matching, 30 R-PCI procedures in 28 patients and 37 M-PCI procedures in 35 patients were analyzed. Clinical success rate with R-PCI was favorable and comparable to M-PCI (93.3 vs. 94.6%, p = 0.97), without any in-hospital MACE. The operator radiation exposure was significantly lower in R-PCI (0 vs. 24.5 µSV, p < 0.0001). Radiation exposure to the patients was tended to be reduced by R-PCI (DAP: 77.6 vs. 100.2 Gycm2, p = 0.07). There were no statistically significant differences in radiation exposure to the assistant, fluoroscopy time, procedural time and contrast volume between the two groups (radiation exposure to the assistant: 10.5 vs. 10.0 µSV, p = 0.64, fluoroscopy time: 27.5 vs. 30.1 min, p = 0.55, procedural time: 72.4 vs. 61.6 min, p = 0.23, and contrast volume: 93.2 vs. 102.0 ml, p = 0.36). R-PCI in selected patients demonstrated favorable clinical outcomes with dramatical reduction of radiation exposure to operators.

Low ankle brachial index predicts poor outcomes including target lesion revascularization during the long-term follow up after drug-eluting stent implantation for coronary artery disease.

BACKGROUND: Peripheral arterial disease (PAD) frequently coexists with coronary artery disease (CAD). The ankle-brachial index (ABI) is widely used for the screening for PAD. Low ABI is associated with short-term clinical outcomes in patients receiving coronary drug-eluting stent (DES) implantation. However, there is no report to examine the relationship between lower ABI and long-term clinical outcomes after DES implantation. Thus, we investigated the clinical long-term impact of low ABI after DES implantation. METHODS: This retrospective analysis included 181 CAD patients treated with DES from April 2010 to March 2013 in our institute. Based on ABI values, we divided the subjects into the low-ABI group　(ABI<0.9, n=29) and the normal ABI group　(0.9≤ABI<1.4, n=152). The incidence of target lesion revascularization (TLR), all-cause mortality, and major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of cardiac death, myocardial infarction, stroke, and any repeat revascularization, were compared between the 2 groups. RESULTS: During the median follow-up period of 43 months, the incidences of TLR, all-cause mortality, and MACCE were significantly higher in the low ABI group than in the normal ABI group (TLR: 41.4% vs 9.9%, p<0.001, all-cause mortality: 31.0% vs 3.9%, p<0.001, MACCE: 48.3% vs 11.2%, p<0.001, respectively). CONCLUSIONS: Low ABI may predict poor long-term outcomes, including TLR, in CAD patients treated with DES.

In Vivo Translation of the CIRPI System: Revealing Molecular Pathology of Rabbit Aortic Atherosclerotic Plaques.

Thin-cap fibroatheroma (TCFA) are the unstable lesions in coronary artery disease that are prone to rupture, resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphologic and biologic features make early detection and risk assessment difficult. We tested our newly developed catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system in vivo to enable detection and characterization of vulnerable plaque structure and biology in rabbit abdominal aorta. Methods: The CIRPI system includes a novel optical probe combining circumferential radioluminescence imaging and photoacoustic tomography (PAT). The probe's CaF2:Eu-based scintillating imaging window captures radioluminescence images (360° view) of plaques by detecting ß-particles during 18F-FDG decay. A tunable laser-based PAT characterizes tissue constituents of plaque at 7 different wavelengths-540 and 560 nm (calcification), 920 nm (cholesteryl ester), 1040 nm (phospholipids), 1180 nm (elastin/collagen), 1210 nm (cholesterol), and 1235 nm (triglyceride). A single B-scan is concatenated from 330 A-lines captured during a 360° rotation. The abdominal aorta was imaged in vivo in both atherosclerotic rabbits (Watanabe Heritable Hyper Lipidemic [WHHL], 13-mo-old male, n = 5) and controls (New Zealand White, n = 2). Rabbits were fasted for 6 h before 5.55 × 107 Bq (1.5 mCi) of 18F-FDG were injected 1 h before the imaging procedure. Rabbits were anesthetized, and the right or left common carotid artery was surgically exposed. An 8 French catheter sheath was inserted into the common carotid artery, and a 0.035-cm (0.014-in) guidewire was advanced to the iliac artery, guided by x-ray fluoroscopy. A bare metal stent was implanted in the dorsal abdominal aorta as a landmark, followed by the 7 French imaging catheters that were advanced up to the proximal stent edge. Our CIRPI and clinical optical coherence tomography (OCT) were performed using pullback and nonocclusive flushing techniques. After imaging with the CIRPI system, the descending aorta was flushed with contrast agent, and OCT images were obtained with a pullback speed of 20 mm/s, providing images at 100 frames/s. Results were verified with histochemical analysis. Results: Our CIRPI system successfully detected the locations and characterized both stable and vulnerable aortic plaques in vivo among all WHHL rabbits. Calcification was detected from the stable plaque (540 and 560 nm), whereas TCFA exhibited phospholipids/cholesterol (1040 nm, 1210 nm). These findings were further verified with the clinical OCT system showing an area of low attenuation filled with lipids within TCFA. PAT images illustrated broken elastic fiber/collagen that could be verified with the histochemical analysis. All WHHL rabbits exhibited sparse to severe macrophages. Only 4 rabbits showed both moderate-to-severe level of calcifications and cholesterol clefts. However, all rabbits exhibited broken elastic fibers and collagen deposition. Control rabbits showed normal wall thickness with no presence of plaque tissue compositions. These findings were verified with OCT and histochemical analysis. Conclusion: Our novel multimodality hybrid system has been successfully translated to in vivo evaluation of atherosclerotic plaque structure and biology in a preclinical rabbit model. This system proposed a paradigm shift that unites molecular and pathologic imaging technologies. Therefore, the system may enhance the clinical evaluation of TCFA, as well as expand our understanding of coronary artery disease.

Pulmonary artery dysfunction in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Unresolved thromboemboli in the pulmonary arteries (PA) is known to cause chronic thromboembolic pulmonary hypertension (CTEPH). However, it remains unknown if vascular dysfunction in pulmonary arteries exists in patients with CTEPH. METHODS AND RESULTS: We enrolled 7 female patients with CTEPH in this study, who have stable pulmonary hemodynamics after balloon pulmonary angioplasty (age; 73.6 ± 3.0 years old, mean right atrial pressure; 4.1 ± 0.4 mm Hg, mean pulmonary arterial pressure; 29.4 ± 2.7, mean pulmonary artery wedge pressure; 8.1 ± 1.2, pulmonary vascular resistance; 397.3 ± 51.7 dynes, cardiac index; 3.1 ± 0.2 L/min/m2). Pulmonary artery vascular function was evaluated by measuring pulmonary artery vasomotion in response to acetylcholine (Ach) at 10-month follow-up after balloon pulmonary angioplasty. All pulmonary vasoactive drugs were discontinued on the day of the procedures. The endothelium-dependent vasomotor response was evaluated by intra-pulmonary artery infusion of Ach at the dose of 10- 8 mol/l, and the vaso-spastic response was at 10- 6 mol/l. We evaluated vasomotor responses at the same segment in each patient, by measuring % changes of luminal area detected by quantitative pulmonary arterial optical frequency-domain imaging (OFDI), where OFDI catheter was fixed during the procedure. Endothelial dysfunction was observed at the dose of Ach at 10- 8 mol/l and vasoconstriction was also confirmed at the dose of Ach at 10- 6 mol/l in the diseased pulmonary arteries in CTEPH. CONCLUSIONS: These results indicated that the pulmonary artery dysfunction exists in patients with CTEPH, which may be involved in the pathogenesis and progression of CTEPH.

Successful Endovascular Treatment of Aortoiliac Bifurcation Stenosis Using an Empirically Based T and Protrude-Stenting with Self- and Balloon-Expandable Stents.

A 73-year-old woman with arteriosclerosis obliterans (ASO) was underwent a crossover stenting for an aortoiliac bifurcation from the right common iliac artery (CIA) with a self-expandable bare-metal stent (SE-BMS); however, a new stenosis later occurred just behind the bifurcation of the left CIA. An ex vivo experiment demonstrated that culotte-stenting by additional implantation of a balloon-expandable bare-metal stent (BE-BMS) through stent struts of the SE-BMS would be empirically infeasible. Although we had initially planned a T-stenting for the additional implantation of a BE-BMS in the left CIA, we finally deployed the stent in the CIA with the proximal end protruding into the previously-implanted SE-BMS through the stent struts to avoid incomplete coverage of the stenosis by reference to the ex vivo experiments. The patient has had no recurrence for 36 months.

Interleukin-1ß is associated with coronary endothelial dysfunction in patients with mTOR-inhibitor-eluting stent implantation.

Implantation of mammalian target of rapamycin (mTOR)-inhibitor drug-eluting stents (DESs) impairs coronary endothelial function. There are no known non-invasive biomarkers of coronary endothelial dysfunction. We aimed to assess the association between serum interleukin-1beta (IL-1ß) and coronary endothelial dysfunction in patients with mTOR-inhibitor DES implantation and to investigate the association between the mTOR pathway and IL-1ß. We enrolled 35 patients who had implanted DESs for coronary artery disease. At a 10-month follow-up, peripheral venous blood samples were collected to measure IL-1ß levels. Coronary endothelial dysfunction was evaluated by intracoronary infusion of incremental doses of acetylcholine. Serum IL-1ß levels were significantly associated with the magnitude of vasoconstriction to acetylcholine at the segment distal (P < 0.05) but not proximal to the stent. Serum IL-1ß levels were positively correlated with stent length (P < 0.05). To examine the direct effects of mTOR inhibition on IL-1ß release, sirolimus was incubated in cultured human umbilical vein endothelial cells (HUVECs) or coronary artery smooth muscle cells (CASMCs). Sirolimus directly increased IL-1ß mRNA expression (P < 0.01) and enhanced IL-1ß release into the culture media (P < 0.01) in CASMCs, but not in HUVECs. Inhibition of mTOR triggers IL-1ß release through transcriptional activation in CASMCs. Serum IL-1ß levels are a potential biomarker for mTOR-inhibitor DES-associated coronary endothelial dysfunction.

Serial changes of coronary endothelial function and arterial healing after paclitaxel-eluting stent implantation.

Several studies have shown coronary endothelial dysfunction and delayed arterial healing associated with first-generation drug-eluting stents. However, it remains unclear whether those issues persist for a longer term. We thus evaluated serial changes in endothelial function and intra-stent condition after paclitaxel-eluting stents (PES) implantation. Eight patients with stable effort angina were assessed at 9 and over 24 months (1st and 2nd follow-up) after PES implantation. Endothelial function was evaluated with intracoronary infusion of acetylcholine (Ach). Vascular responses were quantitatively measured. Intra-stent condition was evaluated using angioscopy. We assessed (1) the degree of neointimal coverage over the stent (grade 0: no coverage to grade 3: full coverage); (2) presence of yellow intima inside the stent, and (3) existence of in-stent thrombus. Vasomotions proximal to the stent at 2nd follow-up significantly improved compared with 1st follow-up (p = 0.04), whereas vascular responses at the distal segment did not differ between 1st and 2nd follow-up (p = 0.19). From the angioscopic study, the average of coverage grading was comparable between the 2 points (0.9 ± 0.8 vs. 1.3 ± 1.0, p = 0.20). In addition, the incidence of yellow intima and in-stent thrombus did not differ between 1st and 2nd follow-up (yellow intima; 50 vs. 37.5 %, p = 1.0, thrombus; 75 vs. 50 %, p = 0.61). Endothelial dysfunction and delayed healing with PES could attenuate gradually, but these issues may persist over 24 months in some patients.

FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs.

The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4KD-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4KD-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs.

Platelet-derived microparticles augment the adhesion and neovascularization capacities of circulating angiogenic cells obtained from atherosclerotic patients.

OBJECTIVE: The neovascularization-related capacities of circulating angiogenic cells (CACs) are impaired in atherosclerotic patients, which may explain the unsatisfactory effects of therapeutic angiogenesis with atherosclerotic patient-derived CACs. Platelet-derived microparticles (PMPs) were reported to augment the re-endothelialization capacity of CACs. Accordingly, we investigated whether PMPs could augment the neovascularization-related capacities of atherosclerotic patient-derived CACs in vitro and in vivo and if so, the associated mechanisms. METHODS AND RESULTS: We isolated mononuclear cells and PMPs from atherosclerotic patient-derived peripheral blood and generated PMP-pretreated CACs (PMP-CACs) by co-culture of the mononuclear cells and PMPs. Although the migration capacity of PMP-CACs was similar to that of CACs, the adhesion capacity of PMP-CACs was greater. PMPs released RANTES into the culture medium, and the receptors were similarly expressed on the surfaces of CACs and PMP-CACs. Intravenous injection of PMP-CACs to rats with hindlimb ischemia augmented neovascularization of the ischemic limbs more than the injection of CACs. The number of PMP-CACs incorporated into the capillaries of the ischemic limbs was greater than that of incorporated CACs. The augmented adhesion and neovascularization capacities by PMP-CACs were canceled out by a RANTES neutralizing antibody. CONCLUSIONS: PMP-secreted RANTES may play a role in the augmenting adhesion and neovascularization capacities of CACs. Injection of PMP-CACs may be a new strategy to augment the effects of therapeutic angiogenesis for limb ischemia in atherosclerotic patients.

Coronary endothelial dysfunction distal to stent of first-generation drug-eluting stents.

OBJECTIVES: This study sought to evaluate the relationship between coronary endothelial function and neointimal coverage after drug-eluting stent (DES) implantation. BACKGROUND: The mechanisms of endothelial dysfunction after DES implantation remain to be fully elucidated. We hypothesized that poor neointimal coverage after DES implantation may be associated with endothelial dysfunction distal to the stent site. METHODS: Sixty-six stable angina patients treated with a first-generation DES were enrolled. At 9-month follow-up, coronary endothelial function was evaluated with intracoronary infusion of incremental doses of acetylcholine (10(-8), 10(-7), and 10(-6) mol/l) and nitroglycerin (200 µg). Vascular responses at the segments proximal and distal to the stent site were angiographically and quantitatively measured. At the same time, the degree of neointimal coverage was evaluated using coronary angioscopy and classified into 4 grades: 0 (no coverage) to 3 (full coverage). RESULTS: We divided the subjects into poor-coverage (grades 0 to 1, n = 33) and good-coverage (grades 2 to 3, n = 33) groups. Acetylcholine induced dose-dependent coronary vasoconstrictions in both groups. At the segment distal to the stent, the magnitude of vasoconstriction to acetylcholine in the poor-coverage group was significantly greater than in the good-coverage group (p < 0.001), whereas vasomotor responses proximal to the stent and vasodilation by nitroglycerine were similar between the 2 groups. CONCLUSIONS: Coronary endothelial dysfunction distal to the stent was associated with poor neointimal coverage after DES implantation.

Ultrasound stimulation restores impaired neovascularization-related capacities of human circulating angiogenic cells.

AIMS: Unsatisfactory effects of therapeutic angiogenesis in critical limb ischaemia may be ascribed to use of circulating angiogenic cells (CACs) derived from atherosclerotic patients with impaired neovascularization-related capacities. We tested whether ultrasound cell stimulation can restore the impaired capacities. METHODS AND RESULTS: During culture of human peripheral blood-derived mononuclear cells for 4 days to achieve CACs, we stimulated the cells in culture daily with low-intensity pulsed ultrasound stimulation (LIPUS). Application of LIPUS to cells in culture derived from healthy volunteers augmented the generation and migration capacities of CACs, increased concentrations of angiopoietin 2 and nitrogen oxides in the culture medium, and increased the expression of phosphorylated-Akt and endothelial nitric oxide synthase in CACs on western blotting. Application of LIPUS to cells in culture derived from atherosclerotic patients also augmented the generation and migration capacities of CACs. Although neovascularization in the ischaemic hindlimb of athymic nude mice was impaired after intramuscular injection of CACs derived from atherosclerotic patients compared with that using CACs derived from healthy volunteers, LIPUS of the cells in culture derived from atherosclerotic patients restored the neovascularization capacities. CONCLUSION: Therapeutic angiogenesis with LIPUS-pre-treated CACs may be a new strategy to rescue critical limb ischaemia in atherosclerotic patients.