Comparison of bolus versus continuous thermodilution derived indices of microvascular dysfunction in revascularized coronary syndromes.

Background: The assessment of coronary microvascular dysfunction (CMD) using invasive methods is a field of growing interest, however the preferred method remains debated. Bolus and continuous thermodilution are commonly used methods, but weak agreement has been observed in patients with angina with non-obstructive coronary arteries (ANOCA). This study examined their agreement in revascularized acute coronary syndromes (ACS) and chronic coronary syndromes (CCS) patients. Objective: To compare bolus thermodilution and continuous thermodilution indices of CMD in revascularized ACS and CCS patients and assess their diagnostic agreement at pre-defined cut-off points. Methods: Patients from two centers underwent paired bolus and continuous thermodilution assessments after revascularization. CMD indices were compared between the two methods and their agreements at binary cut-off points were assessed. Results: Ninety-six patients and 116 vessels were included. The mean age was 64 ± 11 years, and 20 (21 %) were female. Overall, weak correlations were observed between the Index of Microcirculatory Resistance (IMR) and continuous thermodilution microvascular resistance (Rµ) (rho = 0.30p = 0.001). The median coronary flow reserve (CFR) from continuous thermodilution (CFRcont) and bolus thermodilution (CFRbolus) were 2.19 (1.76-2.67) and 2.55 (1.50-3.58), respectively (p < 0.001). Weak correlation and agreement were observed between CFRcont and CFRbolus (rho = 0.37, p < 0.001, ICC 0.228 [0.055-0.389]). When assessed at CFR cut-off values of 2.0 and 2.5, the methods disagreed in 41 (35 %) and 45 (39 %) of cases, respectively. Conclusions: There is a significant difference and weak agreement between bolus and continuous thermodilution-derived indices, which must be considered when diagnosing CMD in ACS and CCS patients.

Changes in absolute flow, myocardial resistance and FFR after chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Randomised studies of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) have shown inconsistent outcomes, suggesting incomplete understanding of this cohort and their coronary physiology. To address this shortcoming, we designed a prospective observational study to measure the recovery of absolute coronary blood flow following successful CTO PCI Aims: We sought to identify patient and procedural characteristics associated with a favourable physiological outcome after CTO PCI. METHODS: Consecutive patients with a CTO subtending viable myocardium underwent PCI utilising contemporary techniques and the hybrid algorithm. Immediately after PCI, and at 3-month follow-up, physiological measurements were performed utilising continuous thermodilution. RESULTS: A total of 81 patients were included with a mean age of 63.6±8.9 years, and 66 (81.5%) were male. Physiological measurements of absolute coronary blood flow in the CTO vessel increased by 30% (p<0.001) and microvascular resistance reduced by 16% (p<0.001) from immediately post-CTO PCI to follow-up assessment. Fractional flow reserve increased by 0.02 (p=0.015) in the same period. Prior coronary artery bypass graft (CABG) and a higher estimated glomerular filtration rate (eGFR) were associated with a larger change in absolute flow. An extraplaque strategy was associated with a smaller change in absolute flow. CONCLUSIONS: Post-CTO PCI, there is a continued augmentation in absolute coronary blood flow and reduction in microvascular resistance from baseline to follow-up at 3 months. Prior CABG and a higher baseline eGFR were predictors of a larger change in absolute coronary flow, whilst an extraplaque final wire path strategy predicted a smaller change. Lastly, the patient characteristics and comorbidities had a larger influence than procedural factors on the observed change in absolute flow.

Novel application of intravascular lithotripsy in stent under-expansion: A single-center experience.

INTRODUCTION: Stent under-expansion due to calcification is associated with a less durable result. The development of intravascular lithotripsy (IVL) has provided clinicians with a readily available, simple-to-use treatment option for coronary calcification, but the use of IVL within a previously stented segment is currently off-license. There are, however, developing data suggesting that the use of IVL can be an effective treatment option for patients with calcific stent under-expansion. METHOD: This was a single-center study of all patients treated with IVL for calcific stent under-expansion between January 2019 and June 2021. The impact of IVL on quantitative coronary angiography (QCA) stenosis and on the minimal stent area (MSA) derived from intracoronary imaging were recorded. The presence of periprocedural complications and adverse cardiovascular events was obtained from the clinical record during the study timeframe. RESULTS: Thirty-nine patients underwent IVL for calcific stent under-expansion during the study time frame with one patient treated with more than one lesion in the same session. In all lesions, there was an improvement in the QCA stenosis with 37 (92.5%) having a residual stenosis of ≤30%. The mean QCA stenosis pre-IVL was 68 ± 21% and following IVL the mean QCA was 18 ± 9% (p < 0.001). In all lesions, there was an improvement in the MSA, with 26 (92.9%) achieving an MSA of more than 4.5 mm2 . The mean MSA pre-IVL was 3.88 ± 1.51 mm2 and following IVL the mean MSA was 7.41 ± 2.34 mm2 (p < 0.001). There were no major procedural complications. Over a mean follow-up of 506 ± 277 days, one patient died from ventricular arrhythmia but there were no other major adverse cardiovascular events. CONCLUSION: This single-center study demonstrates that IVL is a safe and effective treatment for calcific stent under-expansion with good medium-term results.

Morphological and Physiological Characteristics of Ruptured Plaques in Native Arteries and Neoatherosclerotic Segments: An OCT-Based and Computational Fluid Dynamics Study.

Background: Intravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure. Methods: We retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress. Result: Eighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 µm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model. Conclusion: We reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization.

Clinical effectiveness of thrombus aspiration during percutaneous coronary intervention for stent thrombosis in a contemporary setting.

OBJECTIVE: The impact of adjunctive manual thrombus aspiration (TA) in patients with stent thrombosis (ST) treated with percutaneous intervention has not been evaluated in the current era of potent P2Y12 agents and new-generation drug-eluting stents. We sought to assess the effect of TA using data from a large contemporary registry. METHODS: The study population was derived from the Essex ST Investigation Registry (ESTHIR), which contains all consecutive cases of angiographically determined definite ST undergoing interventional treatment in a tertiary cardiac centre between November 2015 and June 2018. Propensity score matching was performed to match patients who underwent TA (TA group) to those who did not (n-TA group). The study endpoints were final TIMI flow and survival free of cardiovascular death (CD) or target lesion revascularisation (TLR). RESULTS: A total of 128 ST patients were included in the present analysis. The mean age was 65 ± 11 years, and 84% were male. About 90% of the patients presented with STEMI, and 85% had very late ST. Seventy-two patients (56%) underwent TA. After propensity score matching, 30 patients were included in each study group. A higher rate of final TIMI III flow was observed in the TA group (TA vs n-TA group, 100% vs 83%), but this difference did not reach statistical significance (p = 0.052). At 1000 days of follow-up, survival free of CD or TLR was not different between the two groups (p = 0.8). CONCLUSION: In a propensity-matched population of ST patients undergoing PCI in a contemporary setting, TA was not associated with improved final TIMI flow or long-term cardiovascular outcomes.

Wall shear stress estimated by 3D-QCA can predict cardiovascular events in lesions with borderline negative fractional flow reserve.

BACKGROUND AND AIMS: There is some evidence of the implications of wall shear stress (WSS) derived from three-dimensional quantitative coronary angiography (3D-QCA) models in predicting adverse cardiovascular events. This study investigates the efficacy of 3D-QCA-derived WSS in detecting lesions with a borderline negative fractional flow reserve (FFR: 0.81-0.85) that progressed and caused events. METHODS: In this retrospective cohort study, we identified 548 patients who had at least one lesion with an FFR 0.81-0.85 and complete follow-up data; 293 lesions (286 patients) with suitable angiographic characteristics were reconstructed using a dedicated 3D-QCA software and included in the analysis. In the reconstructed models blood flow simulation was performed and the value of 3D-QCA variables and WSS distribution in predicting events was examined. The primary endpoint of the study was the composite of cardiac death, target lesion related myocardial infarction or clinically indicated target lesion revascularization. RESULTS: During a median follow-up of 49.4 months, 37 events were reported. Culprit lesions had a greater area stenosis [(AS), 66.1% (59.5-72.3) vs 54.8% (46.5-63.2), p<0.001], smaller minimum lumen area [(MLA), 1.66 mm2 (1.45-2.30) vs 2.10 mm2 (1.69-2.70), p=0.011] and higher maximum WSS [9.0 Pa (5.10-12.46) vs 5.0 Pa (3.37-7.54), p < 0.001] than those that remained quiescent. In multivariable analysis, AS [hazard ratio (HR): 1.06, 95% confidence interval (CI): 1.03-1.10, p=0.001] and maximum WSS (HR: 1.08, 95% CI: 1.02-1.14, p=0.012) were the only independent predictors of the primary endpoint. Lesions with an increased AS (≥58.6%) that were exposed to high WSS (≥7.69Pa) were more likely to progress and cause events (27.8%) than those with a low AS exposed to high WSS (7.4%) or those exposed to low WSS that had increased (12.8%) or low AS (2.7%, p<0.001). CONCLUSIONS: This study for the first time highlights the potential value of 3D-QCA-derived WSS in detecting, among lesions with a borderline negative FFR, those that cause cardiovascular events.

Impact of Intravascular Ultrasound on Chronic Total Occlusion Percutaneous Revascularization.

AIM: We sought to investigate the impact of IVUS use on chronic total occlusion (CTO) PCI using data from a contemporary registry of consecutive patients and applying a propensity score matching analysis. METHODS AND RESULTS: We evaluated 514 successful CTO-PCIs, median age: 67 years (IQR: 58-73), 83.5% males. IVUS-guided PCI was performed in 184 (35.8%) of cases. After using 1:1 propensity matching score analysis, two groups of 182 patients each (IVUS-guided vs. angiography-guided CTO-PCI group) were produced to form the study population. In the IVUS-guided group the median maximum stent diameter was larger and the median total stented segment was longer compared to the angiography-guided group [(3.5 mm, IQR: 3.0-4.0 vs. 3.2 mm, IQR: 3.0-3.5, p < 0.001) and (60.0 mm, IQR: 38.0-91.3 vs. 38.0 mm, IQR: 32.0-70.5, p < 0.001), respectively]. In the IVUS-guided group, retrograde recanalization was more frequently encountered compared to the angiography-guided PCI group (30.2% vs. 20.9%, p = 0.04). Procedural time was significantly longer in the IVUS-guided group, without any difference in fluoroscopy time, radiation dose and contrast volume. Multivariate linear regression analysis showed that IVUS use was the strongest independent factor associated with larger maximum diameter stents (p < 0.001) and a strong independent predictor for total stented segment length during CTO-PCI (p < 0.001). Up to 8 years follow-up, there was no difference in the incidence of the composite endpoint of all-cause death, cardiac death, myocardial infarction and target vessel revascularization between the IVUS-guided PCI and the angiography-guided PCI groups (hazard ratio: 13.7% vs. 15.9%, respectively, log-rank: p = 0.67, median follow-up time: 49.0 months, IQR: 33.0-67.0). CONCLUSIONS: Use of IVUS in CTO-PCI was associated with larger stent diameter and longer stented segments. Despite more frequent use of IVUS in retrograde CTO-PCI, there was no difference in long-term adverse events between IVUS and angiography CTO-PCI groups; nevertheless, the study was not powered to assess clinical outcomes.

Absolute microvascular resistance by continuous thermodilution predicts microvascular dysfunction after ST-elevation myocardial infarction.

AIMS: Continuous thermodilution using intracoronary saline infusion is a novel technique able to provide accurate measurements of absolute coronary blood flow and microvascular resistance (Rmicro). The aim of this study was to assess the ability of Rmicro, measured by continuous thermodilution, to predict microvascular dysfunction in patients with ST-elevation myocardial infarction. METHODS AND RESULTS: In this prospective observational study, continuous thermodilution was used to measure Rmicro in the culprit coronary artery of 32 patients with STEMI (mean age ± SD, 66 ± 10 years; 78% male) immediately post-primary percutaneous coronary intervention (PCI). Concomitant measurements of the index of microvascular resistance (IMR) and coronary flow reserve (CFR) were obtained by bolus thermodilution. Microvascular dysfunction was defined as an IMR > 40 or a CFR < 2. Rmicro was higher in patients with microvascular dysfunction based on the predefined thresholds; for IMR: 863 (IQR, 521-1079) vs 474 (IQR, 337-616) Wood units, p = .004 and for CFR: 633 (IQR, 455-1039) vs 474 (IQR, 271-579) Wood units, p = .02. Receiver-operator characteristic analysis demonstrated that Rmicro was predictive of microvascular dysfunction; area under curve (AUC) 0.800 (95% CI: 0.637-0.963, p = .005) for IMR-defined microvascular dysfunction and AUC 0.758 (95% CI: 0.593-0.924, p = .02) for CFR-defined microvascular dysfunction. An Rmicro threshold of greater than 552 Wood units was optimal for predicting microvascular dysfunction defined by IMR > 40. CONCLUSIONS: Rmicro is able to identify STEMI patients in whom IMR and CFR measurements suggest significant microvascular dysfunction at the end of primary PCI.

Recovery of Absolute Coronary Blood Flow and Microvascular Resistance After Chronic Total Occlusion Percutaneous Coronary Intervention: An Exploratory Study.

Background This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (PCI). Methods and Results In this pilot study, 25 patients scheduled for elective CTO PCI with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution. Measurements were performed immediately after successful CTO PCI and at short-term follow-up. In a subgroup of patients, physiological measurements were performed at the predominant donor vessel before CTO PCI, immediately afterwards, and at follow-up. Absolute coronary blood flow in the recanalized CTO artery increased from 148±53 mL/min immediately after PCI to 221±77 mL/min at follow-up (P<0.001). In agreement, absolute resistance in the myocardial territory perfused by the CTO artery, decreased from 545±255 Wood units immediately after the procedure to 387±128 Wood units at follow-up (P=0.014). There were no significant changes in the absolute coronary blood flow and resistance in the predominant donor between baseline and follow-up. Positive remodeling of the distal CTO vessel with an increase in lumen diameter was observed. Conclusions After successful CTO PCI, blood flow in the recanalized artery and microvascular function of the dependent myocardium are not immediately normal but recover over time.

CASTLE score versus J-CTO score for the prediction of technical success in chronic total occlusion percutaneous revascularisation.

AIMS: We sought to compare the efficiency of the novel EuroCTO (CASTLE) score with the commonly used Multicentre CTO Registry in Japan (J-CTO) score in predicting procedural success of percutaneous coronary intervention (PCI) for coronary chronic total occlusions (CTOs). METHODS AND RESULTS: We evaluated 660 consecutive CTO PCIs (mean age 66±11 years, 84% male). The mean J-CTO and EuroCTO (CASTLE) scores were 1.86±1.2 and 1.74±1.2, respectively. Antegrade wire escalation, antegrade dissection re-entry and retrograde approach were used in 82%, 14% and 37% of cases, respectively. Receiver operating characteristic analysis demonstrated equal overall discriminatory capacity between the two scores (AUC 0.698, 95% CI: 0.653-0.742, p<0.001 for J-CTO vs AUC 0.676, 95% CI: 0.627-0.725, p<0.001 for EuroCTO; AUC difference: 0.022, p=0.5). However, for more complex procedures (J-CTO ≥3 or EuroCTO [CASTLE] ≥4]), the predictive capacity of the EuroCTO (CASTLE) score appeared superior (AUC 0.588, 95% CI: 0.509-0.668, p=0.03 for EuroCTO [CASTLE] score vs AUC 0.473, 95% CI: 0.393-0.553, p=NS for the J-CTO score, AUC difference: 0.115, p=0.04). CONCLUSIONS: In this study, the novel EuroCTO (CASTLE) score was comparable to the J-CTO score in predicting CTO PCI outcome with a superior discriminatory capacity for the more complex cases.

Protected percutaneous coronary intervention with Impella CP in a patient with left main disease, severe left ventricular systolic dysfunction and established hemolysis.

The use of the Impella device in patients with left ventricular (LV) systolic impairment undergoing left main (LM) percutaneous coronary intervention (PCI) has been growing exponentially. Data from observational studies and registries demonstrate that Impella-assisted high-risk PCI is safe and effective with a low rate of peri-procedural complications. Hemolysis is a potential limitation of virtually all mechanical circulatory support devices and a small incidence of hemolysis has been associated with Impella use. The safety and feasibility of Impella use in patients with established hemolysis has not been previously evaluated. We report the first described case in the literature of Impella-assisted left main stem (LMS) PCI in a patient with severe LV systolic dysfunction and autoimmune hemolytic anemia (AIHA). Despite the patient's high bleeding risk (active hemolysis, thrombocytopenia, impaired renal function, use of steroids), Impella placement and PCI were successfully performed without complication. Haemoglobin, bilirubin and lactate dehydrogenase (LDH) levels were closely monitored peri-procedurally with no evidence of exacerbation of the patient's hemolysis. We briefly discuss the mechanism of Impella-induced hemolysis and factors that can exacerbate hemolysis.

Left ventricular twist mechanics and its relation with aortic stiffness in chronic kidney disease patients without overt cardiovascular disease.

BACKGROUND: Recent studies hypothesized left ventricular (LV) twist as a potential biomarker for evaluation of sub clinical myocardial disease, however its relationship with aortic stiffness has yet to be investigated. Chronic kidney disease (CKD) has been identified as a risk factor for both myocardial and arterial disease. As such we sought to explore the relationship between aortic stiffness and LV twist in CKD patients without known cardiovascular disease (CVD). METHODS: In this prospective, observational study we enrolled 106 CKD patients (Stages 1 to 5) with normal LVEF as assessed by conventional echocardiography. Aortic stiffness was measured using aortic pulse wave velocity (aPWV). We defined increased aPWV as ≥10 m/s. LV Twist was measured using two-dimensional speckle tracking echocardiography. RESULTS: Patients with increased aPWV had higher LV twist (p = 0.002) but similar LVEF (p = 0.486). Aortic PWV correlated crudely with age (p < 0.001), the presence of diabetes (p < 0.001), hypertension (p < 0.001), eGFR (p < 0.001), LVMI (p = 0.01), e/e' (p < 0.001) and LV twist (p = 0.003). In multivariable analyses after adjusting for age, gender, cardiovascular risk factors and hypertensive medication, aPWV was independently associated with LV twist (ß = 0.163, p = 0.025). CONCLUSIONS: Aortic stiffness independently associates with LV Twist in asymptomatic CKD patients. These findings suggest a close interaction between LV twist mechanics and arterial remodeling even before CVD becomes clinically relevant.

Everolimus-eluting stent platforms in percutaneous coronary intervention: comparative effectiveness and outcomes.

Despite the remarkable benefits obtained following the introduction of the first-generation drug-eluting stent (DES), concerns were raised over its long-term safety, particularly with regard to very late (beyond 1 year) stent thrombosis. Newer-generation DESs have been developed to overcome this limitation using novel stent platforms, new drugs, more biocompatible durable polymers, and bioabsorbable polymers or backbones. To date, new-generation DESs have virtually replaced the use of first-generation DESs worldwide. In this review article, we discuss in detail the design, pharmacology, and mechanism of action of the newer-generation permanent and bioresorbable everolimus-eluting platforms. Furthermore, we present and evaluate the current evidence on the performance and safety of these devices compared to those of other available stent platforms.

Early detection of subclinical left ventricular myocardial dysfunction in patients with chronic kidney disease.

AIMS: To identify subclinical left ventricular (LV) myocardial dysfunction using speckle tracking echocardiography (STE) in patients with chronic kidney disease (CKD), preserved LV ejection fraction (LVEF), and no cardiovascular history or symptoms. METHODS AND RESULTS: Cross-sectional comparisons of conventional and STE parameters were performed between controls and patients with different stages of CKD. CKD patients were followed up for major adverse cardiovascular events (MACEs). We recruited 106 CKD patients and 38 controls. Mean age was 54.4 ± 15.1 and 36.9 ± 11.5 years, respectively (P < 0.001), with 49.1 vs. 52.6% being female (P = 0.705). There were 29 (27.4%) patients with CKD stages 1/2, 38 (35.8%) with stage 3, and 39 (36.8%) with stages 4/5. Global longitudinal strain (GLS) was more impaired when moving from controls to CKD stages 4/5 (-20.67 ± 3.06, -20.39 ± 2.29, -18.33 ± 3.81, -18.01 ± 2.64, controls vs. CKD stages 1/2, vs. CKD stage 3, vs. CKD stages 4/5, respectively, Padjusted = 0.016), whereas LV twist (16.2 ± 4.8, 18.51 ± 4.36, 19.91 ± 5.35, 24.6 ± 5.35, Padjusted < 0.001) and LV twist rate (101.7 ± 30.3, 110.4 ± 30.1, 121 ± 31.4, 154.8 ± 36.7, Padjusted < 0.001) increased. Risk factor-adjusted GLS (standardized beta ß = -0.245, P = 0.025), strain rate (SR) [global longitudinal strain rates (GLSRs); ß = -0.236, P = 0.019], and early diastolic longitudinal strain rate (GLSRe; ß = 0.247, P = 0.019) were significantly associated with estimated glomerular filtration rate (eGFR), whereas LV twist (ß = -0.432, P < 0.001), LV twist rate (ß = -0.433, P < 0.001), and number of segments with diastolic dysfunction (ß = -340, P < 0.001) were inversely and independently associated with eGFR. Impaired GLS (more than -16%) was observed in almost a quarter of CKD patients and associated with a reduced estimated MACE-free survival at 12-month follow-up (88.5 vs 93.7%, Plogrank = 0.038). CONCLUSION: In CKD patients with no cardiovascular symptoms or history and preserved LVEF, STE can identify subclinical abnormalities of both systolic (decreased GLS and GLSR, increased LV twist, and twist rate) and diastolic (decreased GLSRe and increased number of segments with diastolic dysfunction) LV function.

Angiogenic mediators of the angiopoietin system are highly expressed by CD10-positive lymphoma cells in angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AILT) is a malignant disease of peripheral T-cell origin that is characterized by a prominent proliferation of high endothelial venules in the lymph node. To investigate angiogenic mechanisms in AILT we measured the angiogenic mediator gene expression levels in the lymph nodes of 54 non-Hodgkin lymphoma patients, by immunostaining and quantitative reverse transcription polymerase chain reaction. Angiogenic mediators angiopoietin (Ang) 1 (ANGPT1), Ang2 (ANGPT2) and their receptor, Tie2 (TEK), vascular endothelial growth factor (VEGF; VEGFA) and its receptor, VEGFR2 (KDR), and hepatocyte growth factor (HGF) and its receptor, c-Met (MET) were all more highly expressed in AILT lymph nodes (16 cases) than in B-cell lymphomas (24 cases). Moreover, significantly higher Ang1 and Tie2 expression was detected in AILT cases with CD10-positive neoplastic T-cells by comparison with unspecified peripheral T-cell lymphoma (14 cases). Immunostaining confirmed the expression of Ang1 and VEGF by both neoplastic T-cells and follicular dendritic cells. These results suggest that the angiopoietin system may play an important role in the development of high vascularity in AILT lymph nodes. Consequently, as neoplastic T-cells and follicular dendritic cells are both increased in AILT and may represent an important source of angiogenic mediators, targeting these cells with anti-angiogenic strategies might represent a novel therapy for AILT.