Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.

BACKGROUND: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. METHODS: We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. RESULTS: CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. CONCLUSIONS: For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.

Aterectomía rotacional complicada en una paciente anciana con enfermedad coronaria multivaso. Reporte de caso

La aterectomía rotacional es un procedimiento específico utilizado para el manejo de lesiones coronarias complejas, especialmente cuando existe calcificación de las arterias coronarias (CAC). Esta técnica fue muy utilizada hasta la última década del siglo pasado; actualmente, aunque es poco usada, juega un papel importante en pacientes que podrían ser candidatos a revascularización quirúrgica pero que, por diferentes patologías ―como la enfermedad ateromatosa difusa, en la que se requieren estents largos, reestenosis in-stent, lesiones ostiales calcificadas y oclusiones totales crónicas―, se rechaza la opción quirúrgica. La aterectomía rotacional es un método que utiliza una fresa recubierta de diamante para reducir el volumen de las placas ateroescleróticas y la calcificación de los vasos. Este dispositivo dispersa la placa en microfragmentos, con lo que se consigue un aumento del diámetro luminal. Estos fragmentos, que tienen un diámetro mínimo, pasan predominantemente a la circulación capilar y luego son absorbidos por el sistema reticuloendotelial. Dentro de las complicaciones de esta técnica destacan la disección arterial, el atrapamiento del dispositivo, la bradicardia y la microperforación de arterias coronarias. Esta última puede ser corregida con el uso de trombina, de grasa subcutánea o de perlas. Este artículo reporta el caso de una paciente anciana con enfermedad coronaria multivaso asociada a calcificación extensa de todas las arterias coronarias, por una historia de radioterapia recibida en años anteriores por cáncer de mama y que, al no ser candidata a terapia quirúrgica por cirugía cardiovascular, requirió manejo con aterectomía rotacional que se vio complicada por microperforación de una arteria coronaria, pero que posteriormente evolucionó de manera satisfactoria.

Rotational atherectomy is a specific procedure for managing complex coronary artery lesions, especially when there is coronary artery calcification (CAC). This technique was widely used until the last decade of the 20th century; however, although it is rarely used, it currently plays an important role in patients who could be candidates for surgical revascularization but reject surgeries due to different pathologies-such as diffuse atheromatous disease requiring long stents, in-stent restenosis, calcified ostial lesions and chronic total occlusions. Rotational atherectomy is a method that uses a diamond-coated burr to reduce the volume of atherosclerotic plaques and calcification of vessels. This device breaks up plaque into microfragments, leading to an increase in lumen diameter. These fragments, which have a tiny diameter, pass predominantly into the capillary circulation and are then absorbed by the reticuloendothelial system. Among the complications of this technique are arterial dissection, device entrapment, bradycardia and microperforation of coronary arteries. The latter can be corrected with the use of thrombin, subcutaneous fat or beads. This article reports the case of an elderly female patient with multivessel coronary artery disease associated with extensive calcification of all the coronary arteries secondary to radiotherapy received in previous years for breast cancer. The patient, not being a candidate for cardiovascular surgery, required a rotational atherectomy that resulted in a microperforation of a coronary artery but with good subsequent progress.

Uso de aterectomia rotacional para tratamento de reestenose intra-stent com subexpansão de dupla malha de stents coronarianos. Relato de caso / Use of rotational atherectomy for treatment of in-stent restenosis with coronary double-mesh stent underexpansion. Case report

O tratamento de lesões reestenóticas intra-stent, principalmente as calcificadas, com subexpansão do stent, geralmente requer o uso de técnicas mais complexas para sua execução, como a aterectomia rotacional. O caso se trata de um paciente do sexo masculino com lesão reestenótica focal intra-stent de 99% na origem do primeiro ramo diagonal, local onde foram implantados dois stents há 14 anos. Após falha da angioplastia apenas com balões, realizou-se a ablação da placa e de parte das hastes dos stents pela técnica de aterectomia rotacional, o que possibilitou o implante de novo stent com sua expansão total.

Treatment of in-stent restenosis lesions, especially calcified lesions, with stent underexpansion, generally requires more complex techniques, such as rotational atherectomy. The case reported is a male patient with a 99% in-stent focal restenosis lesion at the origin of the first diagonal branch, where two stents were implanted 14 years ago. After failure of balloon angioplasty alone, ablation of the plaque and part of the stent struts was performed using the rotational atherectomy technique, which allowed the implantation of a new stent which was totally expanded.

Orbital Atherectomy and Heavily Calcified Saphenous Vein Graft Intervention.

Percutaneous coronary intervention in the diseased saphenous vein graft differs significantly from that in the diseased native coronary artery. After being exposed to arterial pressures over time, vein grafts have substantially different plaque characteristics, with more inflammatory cells, more diffuse disease, and less calcification. Severe calcification of saphenous vein grafts, although uncommon, poses a high risk of stent underexpansion. Orbital atherectomy for treatment of de novo calcified coronary lesions has been associated with better outcomes at 5-year follow-up. However, there are no published data on the use of orbital atherectomy to treat severely calcified saphenous vein graft lesions. We present the case of a 77-year-old woman with non-ST-segment-elevation myocardial infarction who underwent successful orbital atherectomy to prepare a severely calcified saphenous vein graft lesion for stent implantation.

Emergent Percutaneous Rotational Atherectomy to Bailout Surgical Transapical Aortic Valve Implantation: A Successful Case of Heart Team Turnaround / Aterectomia Rotacional Percutânea Emergencial para Dar Suporte ao Implante Cirúrgico Transapical da Válvula Aórtica: Um Caso Bem Sucedido de Reviravolta da Equipe Cardíaca

Abstract Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis (AS) in patients with elevated surgical risk. Concomitant coronary artery disease affects 55-70% of patients with severe AS. Percutaneous coronary intervention in patients with TAVI can be challenging. We report a case of acute coronary obstruction immediately following transapical TAVI deployment requiring emergent rotational atherectomy.

Resumo O implante valvar aórtico transcateter (TAVI) é um tratamento estabelecido para estenose aórtica grave (EA) em pacientes com risco cirúrgico elevado. Doença arterial coronariana concomitante afeta 55-70% dos pacientes com EA grave. A intervenção coronária percutânea em pacientes com TAVI pode ser um desafio. Relatamos um caso de obstrução coronariana aguda imediatamente após o implante de TAVI transapical, exigindo aterectomia rotacional emergencial.

Cost-effectiveness of orbital atherectomy compared to rotational atherectomy in treating patients with severely calcified coronary artery lesions in Japan.

Compared to rotational atherectomy (RA), orbital atherectomy (OA) has been shown to decrease procedure failure and reintervention rates in the treatment of severely calcified coronary artery lesions. Our objective was to explore the cost-effectiveness of OA compared to RA in the Japanese healthcare system. A decision-analytic model calculated reintervention rates and consequent total 1-year costs. Effectiveness inputs were therapy-specific target lesion revascularization (TLR) rates and all-cause mortality, pooled from clinical studies. Index and reintervention costs were determined based on claims data analysis of n = 33,628 subjects treated in 2014-2016. We computed incremental cost-effectiveness in Japanese Yen (JPY) per life year (LY) gained based on differences in 1-year cost and projected long-term survival, assuming OA device cost between JPY 350,000 and ​JPY 550,000. OA was found to be associated with improved clinical outcomes (12-month TLR rate 5.0 vs. 15.7%) and projected survival gain (8.34 vs. 8.16 LYs (+0.17), based on 1-year mortality of 5.5 vs. 6.8%). Total 1-year costs were lower for device cost of JPY 430,000 or less, and reached a maximum ICER of JPY 753,445 per LY at the highest assumed device cost, making OA dominant or cost-effective across the tested range, at ICERs substantially below the willingness-to-pay threshold. In conclusion, orbital atherectomy for the treatment of severely calcified coronary artery lesions, compared to rotational atherectomy, is a cost-effective treatment approach in the Japanese healthcare system due to improved clinical performance.

Safety and efficacy of coronary rotational atherectomy in elderly patients with coronary heart disease / 中华老年医学杂志

Objective To analyze the safety and efficacy of coronary rotational atherectomy in elderly patients with coronary heart disease.Methods A total of 107 consecutive patients with coronary artery disease receiving rotational atherectomy from January 2012 to December 2016 were retrospectively analyzed.Patients were divided into an ≥75 years group(n=44)and a ＜75 years group (n=63).We compared the characteristics of rotational atherectomy,peri-procedural complications,instant procedure success rates and 1-year cardiovascular events,including angina,re-infarction,hospitalization due to heart failure,repeat revascularization and cardiac death.Results There was no significant difference in the target coronary vessel,reference vessel diameter,maximal diameter of the burr and ratio of maximal diameter of the burr to reference vessel diameter between the two groups(all P＞0.05).Compared with ＜75 years patients,more ≥75 years patients used 2 burrs(10 cases or 22.7％ vs.4 cases or 6.3％,P =0.013),while there was no significant difference in terms of burr size,rotational time,maximal rotational speed,pre-and post-dilation pressure between the two groups (all P＞0.05).The incidence of peri-procedural complications had no significant difference between the ≥75 years group and the ＜75 years group(8 cases or 18.2％ vs.13 cases or 20.6％,P =0.753).One case of burr entrapment occurred in each group with successful retrieval.The procedure success rate was 96.8％(61 cases)in the ＜75 years group and 100％ in the ≥75 years group(P=0.640).No acute or sub-acute stent thrombosis or urgent coronary artery bypass graft occurred in the two groups during hospitalization.No cardiac death occurred in either group.Conclusions Coronary rotational atherectomy is effective and safe in elderly patients with coronary disease with a high instant procedure success rate.

Managing Stenotic Septal Perforator Branches.

Coronary artery disease of the septal perforator branches can lead to clinical ischemia and conduction abnormalities. Performing interventional procedures in these vessels is frequently impossible because they are small, which makes it difficult to approach them and to select appropriate equipment. Larger septal perforator branches have been treated percutaneously in a few patients; however, the clinical effectiveness and long-term outcomes are not known. We present our experience in managing obstructive septal perforator branch stenosis in 4 patients.

Incidence, Determinants, and Outcomes of Coronary Perforation During Percutaneous Coronary Intervention in the United Kingdom Between 2006 and 2013: An Analysis of 527 121 Cases From the British Cardiovascular Intervention Society Database.

BACKGROUND: As coronary perforation (CP) is a rare but serious complication of percutaneous coronary intervention (PCI) the current evidence base is limited to small series. Using a national PCI database, the incidence, predictors, and outcomes of CP as a complication of PCI were defined. METHODS AND RESULTS: Data were prospectively collected and retrospectively analyzed from the British Cardiovascular Intervention Society data set on all PCI procedures performed in England and Wales between 2006 and 2013. Multivariate logistic regressions and propensity scores were used to identify predictors of CP and its association with outcomes. In total, 1762 CPs were recorded from 527 121 PCI procedures (incidence of 0.33%). Patients with CP were more often women or older, with a greater burden of comorbidity and underwent more complex PCI procedures. Factors predictive of CP included age per year (odds ratio [OR], 1.03; 95% confidence intervals, 1.02-1.03; P<0.001), previous coronary artery bypass graft (OR, 1.44; 95% confidence intervals, 1.17-1.77; P<0.001), left main (OR, 1.54; 95% confidence intervals, 1.21-1.96; P<0.001), use of rotational atherectomy (OR, 2.37; 95% confidence intervals, 1.80-3.11; P<0.001), and chronic total occlusions intervention (OR, 3.96; 95% confidence intervals, 3.28-4.78; P<0.001). Adjusted odds of adverse outcomes were higher in patients with CP for all major adverse coronary events, including stroke, bleeding, and mortality. Emergency surgery was required in 3% of cases. Predictors of mortality in patients with CP included age, diabetes mellitus, previous myocardial infarction, renal disease, ventilatory support, use of circulatory support, glycoprotein inhibitor use, and stent type. CONCLUSIONS: Using a national PCI database for the first time, the incidence, predictors, and outcomes of CP were defined. Although CP as a complication of PCI occurred rarely, it was strongly associated with poor outcomes.

Rotational Atherectomy through Inner Guiding Catheter System for 1.25 mm Rotational Burr Non-Crossable Heavily Calcified Coronary Stenosis

Among the various kinds of percutaneous coronary intervention techniques for balloon non-crossable severe calcified coronary stenosis, rotational atherectomy (RA) is known to be a therapy of choice. We describe a case in which a 1.25 mm RA burr non-crossable heavily calcified stenosis was successfully treated by the RA through '6 in 8 child-mother' guiding technique.

Identificação de genes envolvidos na síntese de proteínas de células musculares lisas com expressão aumentada em placas ateromatosas associados a hiperplasia neointimal após implante de stents não-farmacológicos: estudo GENESIS-R / Identification of genes involved in smooth muscle cell protein synthesis with increased expression in atheromathous plaques associated to neointim al hyperplasia after bare-metal stenting: GENESISI-R Study

Introdução: A reestenose coronária é um fenômeno pouco compreendidoe que permanece como um desafio mesmo na era dos stents farmacológicos. Este estudo tem como objetivo identificar genes envolvidos na síntese de proteínas estruturais e funcionais de células musculares lisas com expressão aumentada em placas ateromatosas de humanos associadosa hiperplasia neointimal após o implante de stents não-farmacológicos. Métodos: Placas ateromatosas foram obtidasmediante aterectomia direcionada, previamente ao implante do stent. A análise da expressão dos genes foi realizada utilizando-se o sistema Affymetrix GeneChip. Os pacientes foramsubmetidos a ultrassom intracoronário 6 meses após o procedimento para análise volumétrica intrastent. Foi avaliada a correlação entre a expressão gênica de placas ateromatosas e o porcentual de hiperplasia intimal intrastent. Resultados: A maioria dos pacientes era do sexo masculino (85,7%), com60,2 ± 11,4 anos de idade, 35,7% eram diabéticos e o porcentual de hiperplasia intimal intrastent foi de 29,9 ± 18,7%.Não houve variação do porcentual de hiperplasia intimal intrastent entre os pacientes com ou sem diabetes (29,5% vs. 30,7%; P = 0,89). Não houve correlação entre a extensão do stent e o porcentual de hiperplasia intimal intrastent (r = -0,26; P = 0,26) ou entre o diâmetro do stent e o porcentual dehiperplasia intimal intrastent (r = 0,14; P = 0,56). Oito genes envolvidos na síntese de proteínas estruturais e funcionais de células musculares lisas apresentaram correlação positiva como porcentual de hiperplasia intimal intrastent. Conclusões: As lesões coronárias de novo apresentam expressão aumentada de genes relacionados com a síntese de proteínas estruturais e funcionais de células musculares lisas associados a futurahiperplasia neointimal intrastent significativa, surgindo como novos alvos terapêuticos.

Long-Term Outcomes after Treatment of Diffuse In-Stent Restenosis with Rotational Atherectomy Followed by Beta-Radiation Therapy with a 188Re-MAG3-Filled Balloon

BACKGROUND AND OBJECTIVES: Intracoronary radiation therapy for in-stent restenosis has been demonstrated to reduce restenosis and major adverse cardiac events. However, the long-term angiographic and clinical outcomes after beta radiation therapy have not been sufficiently evaluated. SUBJECTS AND METHODS: The long-term angiographic and clinical outcomes of 50 consecutive patients who had received beta-radiation therapy with an 188Re-MAG3-filled balloon after rotational atherectomy for diffuse in-stent restenosis (lesion length>10 mm) in native coronary arteries were evaluated. The radiation dose was 15 Gy at a depth of 1.0 mm into the vessel wall. RESULTS: The mean lesion length was 25.6+/-12.7 mm. Radiation was delivered successfully to all patients, without any procedural or in-hospital complications. At the 6-month angiogram, the restenosis rate was 10% (5/50). There were no major adverse cardiac events (MACE), such as death, myocardial infarction or target lesion revascularization (TLR), by the 6-month follow-up. Long-term clinical data were obtained from all patients during 30.1+/-4.5 months of follow-up. No myocardial infarction and one noncardiac death occurred during follow-up. A two-year follow-up angiogram was performed in 26 (58%) of 45 patients that showed a patent radiation segment at the 6-month angiogram. Significant narrowing of the diameter stenosis greater than 50% occurred in 6 (23%) of 26 patients between 6- and 24-months after the beta-radiation. Late TLR was performed in 6 patients. The rate of 30-month death-free survival and MACE-free survival were 98.0+/-2.0 and 86.9+/-5.0%, respectively. CONCLUSION: Beta-radiation using an 188Re-MAG3-filled balloon after rotational atherectomy is associated with favorable long-term angiographic and clinical outcomes.

Clinical Aspects of Coronary Artery Perforation during Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: Coronary artery perforation is a rare, but potentially deadly, complication of percutaneous coronary intervention (PCI). The purpose of this study was to analyze the clinical characteristics, and outcome, of coronary artery perforation. SUBJECTS AND METHODS: We retrospectively reviewed 3,782 consecutive PCIs, performed between January, 1994 and May, 2002 at the Samsung Medical Center, from the database records. The medical records and angiograms of the patients were also reviewed. The coronary artery perforations were classified according to Ellis' classification. RESULTS: A coronary artery perforation was noted in 24 patients (0.6%). It was most commonly observed during PCI of the right coronary artery (46%) and a chronic total occlusion intervention (42%). The number of the patients with Ellis'classes I, II and III were 11, 8 and 5, respectively. The most frequent causes of the perforation were guidewire, followed by balloon (11 and 8 cases, respectively). The interventional modality with the highest risk of perforation in this study was rotational atherectomy, (4 out of 157, 2.6%). Five patients had cardiac tamponade, of which four occurred during a rotablator procedure. Pericardiocentesis was performed in 5 patients, while 3 patients with class III perforations received emergent coronary artery bypass surgery. There were no in-hospital mortalities, although the duration of the hospital stay for the class III patients was longer than those with classes I or II perforations. CONCLUSION: A coronary artery perforation during percutaneous coronary intervention is a potentially serious complication. However, the immediate and adequate management results in a fairly good prognosis.