Stefan Betge

Paclitaxel-eluting stents for the treatment of chronic total coronary occlusions: A strategy of extensive lesion coverage with drug-eluting stents

The recanalization of a chronic total coronary occlusion (CTO) is hampered by a high rate of lesion recurrence. The goal of the present study is to assess the effect of paclitaxel‐eluting stents in CTOs in a strategy of extensive stent coverage and the optional use of additional bare metal stents (BMSs). In 82 consecutive patients, a CTO (duration > 2 weeks) was successfully recanalized with implantation of one or more Taxus stents. These patients underwent a repeat angiography after 5.0 ± 1.5 months and were assessed by quantitative angiography. The patients were compared with 82 clinically and lesion‐matched patients from a consecutive series of 148 patients with CTOs treated by BMS in the preceding time period. In 21 of the 82 patients, additional lesions in the target artery not directly related to the original occlusion site were treated with BMSs (hybrid approach). The history of diabetes, extent of coronary artery disease, clinical symptoms, and angiographic features were similar in the Taxus and BMS group. Periprocedural adverse events were 3.3% with Taxus and 3.3% with BMS, but 12 months MACE was significantly lower in the group with exclusive use of Taxus (13.3% vs. 56.7%; P < 0.001), mainly due to a lower target lesion revascularization of 10.0% as compared to 53.4% (P < 0.001). There was only one late reocclusion with Taxus (1.7%) as compared to 21.7% with BMS (P < 0.05). However, in the hybrid group, the MACE rate was considerably higher, with 33.3%. Our data of a 80% reduction of target vessel failure as compared to BMS, with a lower risk of late reocclusions without increased acute adverse events, demonstrate the benefit of paclitaxel‐eluting stents in CTOs. However, diffuse atherosclerosis in CTOs should be covered completely by the drug‐eluting stents.

Determinants of target vessel failure in chronic total coronary occlusions after stent implantation: The influence of collateral function and coronary hemodynamics

OBJECTIVES The goal of this study was to assess the influence of collateral function, coronary hemodynamics, and the angiographic result on the risk of target vessel failure (TVF) after recanalization of a chronic total coronary occlusion (CTO). BACKGROUND Collaterals may have an adverse effect on TVF. METHODS In 111 consecutive patients, a CTO (duration >2 weeks) was successfully recanalized with stent implantation. Collateral function was assessed by intracoronary Doppler flow velocity and pressure recordings distal to the occlusion. Baseline collateral function was determined before the first balloon inflation, and recruitable collateral function after stenting during a balloon reocclusion. Finally, the coronary flow velocity reserve (CFVR) and the fractional flow reserve (FFR) were measured. RESULTS Angiographic follow-up after 5 +/- 4 months in 106 patients showed a reocclusion in 17% and a restenosis in 36%. The major determinants of TVF were the stent length (p < 0.01) and number of implanted stents (p < 0.01). No difference was observed in baseline or recruitable collateral function between patients with and without TVF; 52% of patients had a CFVR >or= 2.0, and only 18% a CFVR >or=2.5 after percutaneous transluminal coronary angioplasty, but neither cutoff-value predicted TVF. A low FFR discriminated patients with reocclusion (0.81 +/- 07 vs. 0.86 +/- 08, p < 0.05) but not with restenosis (0.87 +/- 0.06). CONCLUSIONS This study showed that there is no relation between a well-developed collateral supply and the risk of TVF in recanalized CTOs. This was rather determined by the stented segment length. There was also no adverse effect of the frequently observed impaired CFVR on TVF, whereas a low FFR was associated with a higher risk of reocclusion.

Combined magnetic resonance imaging of deep venous thrombosis and pulmonary arteries after a single injection of a blood pool contrast agent.

ObjectiveAgreement rate between magnetic resonance imaging (MRI) and Doppler ultrasound (DUS) for the detection of deep vein thrombosis (DVT) in the lower extremities was attempted by using the intravascular MRI contrast agent gadofosveset trisodium. The potential of this method to detect pulmonary embolism (PE) was also evaluated.Material and MethodsForty-three consecutive inpatients with ultrasound-confirmed DVT but no clinical signs of PE were prospectively enrolled in this feasibility study. MRI was performed after a single injection of gadofosveset trisodium. The pulmonary arteries were imaged using a 3D Fast Low Angle Shot (FLASH) gradient recalled echo sequence. Additionally, pulmonary arteries, abdominal veins, pelvic and leg veins were imaged using a fat-suppressed 3D gradient echo Volume Interpolated Breath-hold Examination (VIBE FS).ResultsGadofosveset trisodium-enhanced MRI detected more thrombi in the pelvic region, upper leg and lower leg than the initial DUS. In addition, PE was detected in 16 of the 43 DVT patients (37%).ConclusionThis study shows the feasibility of a combined protocol for the MRI diagnosis of DVT and PE using gadofosveset trisodium. This procedure is not only more sensitive in detecting DVT compared to standard DUS, but is also able to detect PE in asymptomatic patients.

Simulated temporary hypoxia triggers the release of CD31+/Annexin+ endothelial microparticles: A prospective pilot study in humans

INTRODUCTION Endothelial microparticles (EMP) are small membrane vesicles that originate from activated or apoptotic endothelial cells. Although the exact mechanism of EMP function is still relatively unknown, it has been shown that they modulate inflammatory processes, coagulation and vascular function. In this study we hypothesized that transient hypoxia may act as a trigger for the release of EMP into circulation. MATERIALS AND METHODS Fourteen healthy volunteers were subjected to transient normobaric hypoxia in an air-conditioned chamber simulating an oxygen concentration of a height of up to 5500 meters. Blood samples were evaluated for EMP using flow cytometry. RESULTS During the experiment oxygen concentration was adjusted to a value equivalent to a height of 5500 meters to achieve hypoxic conditions. Oxygen saturation decreased to 78% . At the final height a significant increase of CD31+/Annexin+ EMP levels was evident (increase from 0.03% ± 0.01% SEM to 0.12% ± 0.04% SEM, p = 0.0188). CONCLUSIONS These experimental results show that temporary hypoxic conditions can trigger the release of CD31+/ Annexin+ EMP also in healthy volunteers. In our previous studies we have shown that apoptotic bodies can confer pro-survival signals to cardiomyocytes during myocardial ischemia. Based on the experimental results of this current study we believe that the release of CD31+/Annexin+ EMP during hypoxia might act as an endogenous survival signal.

Magnetic resonance VIBE venography using the blood pool contrast agent gadofosveset trisodium—An interrater reliability study

PURPOSE In this study, image quality of leg veins and vena cava inferior was scored by independent raters using the new intravascular magnetic resonance imaging (MRI) contrast agent gadofosveset trisodium using fat-suppressed 3D gradient echo Volume Interpolated Breath-hold Examination. MATERIAL AND METHODS The leg venous system without clinical signs of deep venous thrombosis (DVT) and sonography-ruled out DVT were imaged using a fat-suppressed 3D gradient echo Volume Interpolated Breath-hold Examination (VIBE FS). Image interpretation was done independently by two experienced radiologists (raters) using a 5-point scoring system. RESULTS High diagnostic image quality with an overall mean visibility score of 4.8±0.1 was acquired in patients enrolled in the study using gadofosveset trisodium-enhanced MRI for the venous system of the leg. There were no cases with moderate, poor or nondiagnostic image quality. Additionally, an excellent interrater reliability was observed. CONCLUSIONS This study shows the feasibility of acquiring high resolution images with excellent image quality of the venous system of the leg using gadofosveset trisodium.

Recruitment of circulating dendritic cell precursors into the infarcted myocardium and pro-inflammatory response in acute myocardial infarction.

DC (dendritic cells) play an important role in the immune system. They invade peripheral tissues to detect harmful antigens, inducing a local immune response. Studies suggest that DCPs (dendritic cell precursors) might be reduced in AMI (acute myocardial infarction); however, the reason for their reduction is unknown yet. In the present study, circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs), tDCPs (total DCPs) and serum levels of TNFα (tumour necrosis factor α), IL (interleukin)-2, -4, -5, -6, -10 and -12 were analysed by flow cytometry in blood of patients with NSTEMI [non-STEMI (ST-segment elevation myocardial infarction)] (n=44) and STEMI (n=34) compared with controls with excluded CAD (coronary artery disease) (n=45). Post-mortem myocardial specimens of patients with AMI (n=12) and healthy myocardium of accident victims (n=10) were immunostained for mDCs (myeloid dendritic cells) T-cells and macrophages. Compared with controls, in patients with AMI a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.0001). The extent of the decrease was higher in STEMI than NSTEMI patients. Serum levels were significantly higher in patients with AMI compared with controls for IL-6, -10, -12 and TNFα (each P<0.03). Immunostaining revealed significantly higher number of DCs, T-cells and macrophages (each P<0.002) in infarcted than control myocardium. We show that circulating DCPs are significantly reduced in AMI, with a pronounced reduction in STEMI patients. This was accompanied by a significant increase of inflammatory serum cytokines in patients with AMI. Immunohistochemical analysis unravelled that the reduction of circulating DCPs might be due to recruitment into the infarcted myocardium.

The association between endothelial microparticles and inflammation in patients with systemic sclerosis and Raynaud's phenomenon as detected by functional imaging.

UNLABELLED Systemic sclerosis (SSc) is a systemic, autoimmune connective tissue disease characterized by vasculopathy and microvascular changes. Fluorescence Optical Imaging (FOI) is a technique used to assess inflammation in patients with arthritis; in this study FOI is used to quantify inflammation in the hand. Endothelial Microparticle (EMP) can reflect damage or activation of the endothelium but also actively modulate processes of inflammation, coagulation and vascular function. The aim of the present study was to quantify EMP and FOI, to determine an association between these microparticles and inflammation and to endothelial function. METHODS EMP were quantified in plasma samples of 25 patients (24 female, 1 male, age: 41 ± 9 years) with SSc using flow cytometry. EMP was defined as CD31+/CD42- MP, and CD62+ MP. Perivascular inflammation was assessed using fluorescence optical imaging (FOI) of the hand. Macrovascular endothelial function was non-invasively estimated using the Endopat system. RESULTS Plasma levels of CD31+/CD42- EMP and CD62+ EMP were lower in patients with SSc compared to controls (both p <  0.05). An impaired endothelial function with an increased hyperemia index was observed. A strong association could be demonstrated between CD62+ EMP and perivascular soft tissue inflammation as assessed by the FOI global score (Spearman, p = 0.002, r = 0.61). CONCLUSIONS EMP indicate molecular vascular damage in SSc; in this study a strong association between EMP and perivascular inflammation as quantified by FOI is demonstrated. Consequently EMP, using FOI, may be a potential marker benefitting the diagnosis and therapy monitoring of patients with SSc with associated Raynauds phenomenon.

Positive effect of eplerenone treatment on endothelial progenitor cells in patients with chronic heart failure

Background: Endothelial progenitor cells (EPCs) are known to play a significant role in reendothelialization and vascular repair. Recently, a mineralocorticoid receptor was demonstrated to be expressed by EPCs. The study aimed to evaluate a potential influence of eplerenone treatment on the total number of EPCs in patients with chronic heart failure. Methods: Eighty-seven male patients with chronic heart failure were included (age: 23–83 years; body mass index 29.1 ± 5.1 kg/m2; New York Heart failure classification (NYHA) I: 29 patients, NYHA II: 32 patients, NYHA III: 26 patients). Numbers of circulating EPCs were quantified immediately using flow cytometry. Twenty-eight patients received therapy with eplerenone. Patients were further characterized by echocardiography, spirometry and laboratory markers. Results: Patients with ongoing eplerenone administration showed higher levels of circulating cells expressing CD34+ (p<0.05) and CD34+KDR+ (p<0.05) and CD34+CD133+KDR+ cells (p<0.05). The effects of eplerenone treatment could be shown to be independent of NYHA status, genesis of the underlying cardiovascular morbidity, left ventricular function and co-medication. Conclusion: Patients with chronic heart failure treated with eplerenone show higher numbers of EPCs. The clinical benefit for treatment with eplerenone has been demonstrated even for patients with mild heart failure and might be partially mediated by EPCs.

Testosterone deficiency in male heart failure patients and its effect on endothelial progenitor cells.

Background: Endothelial progenitor cells (EPCs) are thought to contribute to reendothelialization and neoangiogenesis. Since it is known that EPCs express a testosterone receptor, we wanted to assess the prevalence of testosterone deficiency in patients with CHF and its impact on circulating EPCs. Methods: 137 male patients with chronic heart failure (CHF) were included (age 61 ± 13 years; BMI 29 ± 5 kg/m2; New York Heart Association classification (NYHA) I: n = 47, NYHA II: n = 51, NYHA III: n = 39). Numbers of different populations of circulating EPCs were quantified using flow cytometry. Levels of free testosterone and EPC-regulating cytokines were determined using ELISA. Results: The prevalence of testosterone deficiency in our University CHF clinic was 39%. However, there was no difference between patients with and without testosterone deficiency regarding their levels of EPCs. Testosterone levels were inversely correlated with age (R2 = −0.32, p = 0.001) and NYHA status (R2 = 0.28, p = 0.001) and correlated with cardiorespiratory capacity (R2 = 0.26, p = 0.03). Conclusion: Testosterone deficiency is frequent in male patients with CHF but does not appear to impact the regenerative EPCs.

Delayed recovery of left ventricular function after recanalization of a chronic coronary occlusion

An unusually prolonged course of recovery of severely impaired left ventricular (LV) function (EF 32%) was observed in a patient after recanalization of a chronically occluded LAD. Despite persistent vessel patency, LV function remained depressed for almost 2 years after the percutaneous transluminal coronary angioplasty until complete recovery (EF 82%) could be observed. The possibility of a delayed recovery should be considered when assessing new therapeutic strategies to improve LV function of chronically ischemic myocardium. Catheter Cardiovasc Interv 2003;60:491–495.