Analysis of endovascular therapy for peripheral arterial disease in all German hospitals.

Background: The quality of vascular care has significantly improved in part by the expansion of endovascular techniques for the treatment of symptomatic peripheral artery disease (PAD) in recent years. In Germany these are primarily provided by the three disciplines of vascular surgery, angiology, and interventional radiology (IR). However, the relative contribute of angiologists to the total number of cases performed is unknown. Patients and methods: In the present study, we analysed the respective contribution of vascular surgery, angiology, and IR to the delivery of endovascular revascularisations in symptomatic PAD in Germany based on the legally mandatory quality reports representative for the reporting year 2018. Results: Vascular surgery is the most common speciality reporting procedures in German hospitals (n=579; 25.1%), followed by IR (n=264; 11.5%), angiology (n=189; 8.2%) and cardiology (n=17; 0.7%). The combination of vascular surgery and IR was reported in 202 (8.8%), vascular surgery and angiology in 167 (7.2%) and angiology and IR in 65 (2.8%) hospitals, and 63 (2.7%) hospitals reported the combination of all three disciplines. Not every department performed catheter interventions. The analysis of procedures per centre revealed that angiology centres provided the highest numbers for both basic procedures and more complex techniques such as atherectomy, rotational thrombectomy, lithoplasty, selective thrombolysis or the use of re-entry devices. In total, angiology centres provided 24.4% of the total procedures or 23.9% of the so-called basic procedures as a surrogate for patient numbers. Conclusions: While each of the disciplines contribute significantly to the endovascular procedures, angiology centres perform more procedures per centre and more complex procedures than the other disciplines highlighting the important quantitative and qualitative contribution of angiology specialists to the care of vascular patients. The inpatient catheter interventional care of patients with PAD is still too rarely carried out in a multi-disciplinary manner in Germany.

Endovascular interventions in outpatient care.

Endovascular arterial revascularisations for the treatment of symptomatic peripheral arterial disease are constantly increasing in importance and number due to the changing age structure and high numbers of comorbidities in the German population. Patients with peripheral artery disease are often at increased risk for peri- and post-procedural complications including severe cardiovascular events. Due to limited financial and human resources and considerable risks of hospitalization, endovascular interventions that were previously reserved for hospitalized patients are now progressively considered to be performed as day case procedures. More than one third of these procedures are performed in Germany by internists with a specialization in angiology. In the current position paper the German Society of Angiology endorsed by the European Society of Vascular Medicine, summarizes the requirements and risk factors to be considered for the planning, safe performance and post procedural care of endovascular revascularizations in outpatients. The performance of endovascular procedures for peripheral artery disease both in hospitalised and outpatients should be accompanied by a mandatory quality assurance process that should not only capture procedural data, but also require documentation of complications and longterm outcome.

Stents With Torsional Strength for Superficial Femoral Artery Disease: The Prospective Q3-Registry.

PURPOSE: This postmarketing surveillance study aimed to assess effectiveness and safety of a peripheral self-expanding stent with high torsional strength (POLARIS stent) for the treatment of de novo superficial femoral artery (SFA) lesions in the routine clinical practice. MATERIALS AND METHODS: Consecutive patients with symptomatic de novo SFA occlusive disease who underwent POLARIS stent implantation were enrolled into the prospective, multicenter, observational postmarket surveillance study. Primary outcome measure was freedom from clinically driven target lesion revascularization (cdTLR) at 12 months. Main secondary outcomes were procedural success, primary clinical improvement, and freedom from major adverse cardiovascular and limb events (MACLE) throughout 24 months. RESULTS: A total of 199 participants (70±11 years, 70.4% men) were included in the study at 9 German sites from December 2014 to August 2018. Half of them (52.6%) were current smokers, 37.6% had diabetes, and 25.0% were obese. Most participants suffered from intermittent claudication (88.4%). Mean lesion length was 98±83 mm, 43.5% of lesions were occluded, and 27.3% were severely calcified. Freedom from 12 months cdTLR was 94.4% (95% confidence interval [CI], 90.6-98.2). At 24 months, freedom from cdTLR was 88.7% (95% CI, 83.0-94.4). Procedural success was achieved in 96.2% of participants. Primary clinical improvement occurred in 87.5% and 85.4% of participants at 12 and 24 months, respectively. Freedom from MACLE was 94.8% (95% CI, 91.4-98.1) and 93.8% (95% CI, 89.9-97.6) at 12 and 24 months, respectively. CONCLUSIONS: Treatment of SFA occlusive disease in a real-world setting using the POLARIS stent with high bidirectional torsional strength is efficacious and does not raise any safety concern in the medium term. The study is registered with ClinicalTrials.gov (Identifier: NCT02307292).

Influence of Macitentan on the Vascular Tone and Recruitment of Finger Capillaries Under Hypobaric Hypoxia in High Altitude.

Betge, Stefan, Stefan Drinda, Thomas Neumann, Laura Bäz, Alexander Pfeil, Christian Schulze, Ralf Mrowka, Christian Jung, and Marcus Franz. Influence of macitentan on the vascular tone and recruitment of finger capillaries under hypobaric hypoxia in high altitude. High Alt Med Biol. 21:336-345, 2020. Introduction: Acute normobaric (NH) and hypobaric hypoxia (HH) has effects on the vascular tone of larger arteries and may have effects on the microcirculation. These effects may be noninvasively detectable by automated devices. A part of these effects may be mediated by endothelin (ET) and should be influenced by macitentan (MAC), a dual endothelin receptor antagonist (ERA). Methods: We used photoplethysmographic sensors, fingertip volume sensors, nailfold capillaroscopy, and laser Doppler probes at rest and after a 5-minute forearm ischemia in healthy study subjects under NH, under HH, and under HH plus a single dose of MAC. Results: NH at simulated 4000 m led to increased heart rates (HR) and pulse wave velocities (PWV) and reduced augmentation index (AIX). The values for the AIX showed a high SD and differed between the used devices. At simulated 5500 m, only baseline mean value (BMV; EndoPAT) showed a further change, indicating less filled capillaries of the fingertips. HH (2978 m) increased HR, blood pressure values, and PWV. Focusing on the microcirculation of the fingertips, HH reduced the BMV and the nailfold capillary density and the postischemic capillary recruitment. MAC had no effect on the BMV, but antagonized the effects of HH on the nailfold capillaries and led to a strongly increased postischemic diameter of the arterial limbs. Concordantly, the postischemic blood flow velocity increment, measured through ultrasound Doppler, was increased at ALT+MAC. Conclusions: The BMV may be a parameter for changes of the microcirculation of the finger tips. A single dose of MAC blocked hypoxia-induced capillary rarefaction and enhanced postischemic hyperemia of the fingertips. These results indicate the importance of ET-1 for the regulation of the microcirculation under hypoxia. The German Registry of Clinical Studies (DRKS) ID: 00005459.

Effectiveness of the Pulsar-18 self-expanding stent with optional drug-coated balloon angioplasty in the treatment of femoropopliteal lesions - the BIOFLEX PEACE All-Comers Registry.

Background: Previous studies showed favorable results after treatment of femoropopliteal lesions with the Pulsar-18 self-expanding (SE) nitinol stent. The objective of this registry was to evaluate whether these results will be confirmed in a real-world setting with varying stenting strategies. Patients and methods: In this prospective, observational trial, 160 patients with 186 femoropopliteal lesions were treated with the Pulsar-18 SE nitinol stent at 9 German sites. Mean lesion length was 116 ± 103 mm, and 41.9 % of the lesions were moderately or heavily calcified. Eighty lesions were concomitantly treated with drug-coated balloon (DCB). Main effectiveness outcome was primary patency at 12 months, and main safety outcome was freedom from the composite of device or procedure related death, major target limb amputation, and clinically driven target lesion revascularization (TLR) at 30 days and 6 months. Results: Kaplan-Meier estimate of primary patency was 89.1 %, 67.3 %, and 57.1 % at 6, 12, and 24 months. Freedom from TLR was 95.5 %, 91.4 %, and 85.2 % at 6, 12, and 24 months, respectively. Lesions, which were additionally treated with DCB (plus DCB-group), were longer (150 versus 82 mm on average, p < 0.0001), and associated with lower primary patency estimates than those without DCB angioplasty (stent-only-group) (log-rank p = 0.006). However, there was no difference in freedom from TLR between groups (log-rank p = 0.542). Improvement by ≥ 1 Rutherford category was achieved in 84.8 %, 81.0 %, and 81.7 % of patients at 6, 12, and 24 months, respectively. Walking distance and patient-reported pain improved persistently through 24 months (p < 0.001). Hemodynamic improvement was achieved in 68.2 %, 73.7 %, and 70.7 % of the patients at 6, 12, and 24 months, respectively. Conclusions: The Pulsar-18 self-expanding nitinol stent with optional drug-coated balloon angioplasty can be considered an efficacious and safe therapy option for endovascular treatment of femoropopliteal artery disease.

Analysis of novel cardiovascular biomarkers in patients with peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) is a common form of manifestation of atherosclerosis. PAD has a considerable impact on morbidity, hospitalization rates and health-care costs. Biomarkers have been introduced in many cardiovascular disease entities over the last years. However, an analysis on the correlation of biomarker levels and PAD is still lacking. METHODS: A total of 106 patients were enrolled in this current study, 51 that were diagnosed with PAD and 55 with excluded coronary and peripheral artery disease as controls. During outpatient visits, plasma samples of all patients were obtained and analyzed for sST2 (hemodynamics and inflammation), galectin-3 (fibrosis and remodeling), GDF-15 (remodeling and inflammation), suPAR (inflammation), and fetuin-A (vascular calcification) by use of ELISA after informed consent. RESULTS: Compared with controls, patients with PAD showed significantly higher levels of sST2 (5248 vs. 7503 pg/mL, P<0.001), suPAR (2267 vs. 2414 pg/mL, P=0.02), galectin-3 (2795 vs. 4494 pg/mL, P<0.001), and GDF-15 (549 vs. 767 pg/mL, P<0.001). Fetuin-A showed a trend towards lower levels in patients with PAD (117 vs. 100 ng/mL, P=0.119). CONCLUSIONS: Circulating levels of sST2, suPAR, galectin-3, and GDF-15 were significantly elevated in PAD patients. In contrast, fetuin-A levels showed a decrease in PAD patients indicating increased vascular calcification. Thus, by incorporating different pathophysiological processes present in PAD, tested novel biomarkers facilitate a more precise diagnosis as well as a more accurate evaluation of disease severity and progression.

Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension.

Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg) is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague-Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose). There were three experimental groups: sham-treated controls (control group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13). ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys) was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg) compared to the control group (41 ± 15 mmHg, p = 0.002) accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001). Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01). Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006) and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022). PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH.

Acute effects of moderate altitude on biomarkers of cardiovascular inflammation and endothelial function and their differential modulation by dual endothelin receptor blockade.

BACKGROUND: Endothelial dysfunction is accompanied by the release of microparticles (MP). OBJECTIVE: We sought to investigate the effect of moderate hypoxia on circulatory levels of microparticles, biomarkers of cardiovascular function and inflammation and on echocardiographic parameters in healthy volunteers staying at an altitude of 2978 m. METHODS: Eighteen healthy volunteers were subjected to moderate hypoxia by staying at 2978 m above sea level for three days. Blood samples were evaluated for MP using flow cytometry. ELISA analysis was performed for sST2, H-FABP, suPAR and GDF-15. Moreover, the effect of dual endothelin-receptor blockade was investigated. RESULTS: Oxygen saturation decreased to 93%. A significant decrease of endothelial and platelet MP levels was found. These results were corroborated by a similar response in sST2 and suPAR plasma concentration. Endothelin-receptor blockade by macitentan only had a marginal influence on MP, sST2, H-FABP, suPAR and GDF-15 levels, though it led to a significant amelioration of echocardiographic parameters of right heart function. CONCLUSIONS: These experimental results show that moderate hypoxia due to altitude exposition led to a reduction in parameters of endothelial dysfunction as shown by a decrease in endothelial and platelet MP, sST2 and suPAR levels. A slight increase in pulmonary pressure at moderate altitude was decreased by dual endothelin receptor blockade.

Predictive value of the augmentation index derived vascular age in patients with newly diagnosed atherosclerosis.

Early detection of atherosclerosis, i.e., in occupational health screening programs could reduce the rate of cardiovascular events in the working population. Changes of the augmentation index (AIX) correlate with changes of the arterial stiffness induced by aging, atherosclerosis, or arterial hypertension and have a prognostic value for cardiovascular events. Their diagnostic yield should be increased by normalizing the AIX to age, in terms of a calculating the vascular age (VA). In this pilot study, 30 patients (mean age 65.3 ± 8.8 years, 21 male) with suspected coronary heart disease underwent a duplex ultrasound of the carotid arteries and a measurement of the ankle brachial index in addition to the coronary angiography. The AIX was recorded with a portable device (Vascular Explorer), and the VA was calculated. Atherosclerosis was found in 24 patients. They were older than the patients without atherosclerosis, but there was no age dependency found for the distribution pattern or severity of atherosclerosis. In patients with findings of atherosclerosis, the calculated VA was higher than the chronological age, and these differences were significant in patients below 65 years of age. Comparing patients in higher blood pressure classes with patients in lower classes, significantly higher AIX, VA, and differences to the chronological age were found. The VA, deduced from the noninvasively obtained AIX, is a promising candidate for screening programs for atherosclerosis, i.e., in occupational health screening programs.

Lung tissue remodelling in MCT-induced pulmonary hypertension: a proposal for a novel scoring system and changes in extracellular matrix and fibrosis associated gene expression.

Pulmonary hypertension (PH) is associated with vasoconstriction and remodelling. We studied lung tissue remodelling in a rat model of PH with special focus on histology and extracellular matrix (ECM) remodelling. After induction of PH by monocrotaline, lung tissue was analysed histologically, by gene expression analysis and immunofluorescence labelling of ED-A domain containing fibronectin (ED-A+ Fn), B domain containing tenascin-C (B+ Tn-C) as well as alpha-smooth muscle actin (α-SMA). Serum concentrations of ED-A+ Fn were determined by ELISA. Systolic right ventricular pressure (RVPsys) values were significantly elevated in PH (n = 18; 75 ± 26.4 mmHg) compared to controls (n = 10; 29 ± 19.3 mmHg; p = 0.015). The histological sum-score was significantly increased in PH (8.0 ± 2.2) compared to controls (2.5 ± 1.6; p < 0.001). Gene expression analysis revealed relevant induction of several key genes of extracellular matrix remodelling. Increased protein deposition of ED-A+ Fn but not of B+ Tn-C and α-SMA in lung tissue was found in PH (2.88 ± 3.19 area%) compared to controls (1.32 ± 0.16 area%; p = 0.030). Serum levels of ED-A+ Fn were significantly higher in PH (p = 0.007) positively correlating with RVPsys (r = 0.618, p = 0.019). We here present a novel histological scoring system to assess lung tissue remodelling in PH. Gene expression analysis revealed induction of candidate genes involved in collagen matrix turnover, fibrosis and vascular remodelling. The stable increased tissue deposition of ED-A+ Fn in PH as well as its dynamics in serum suggests a role as a promising novel biomarker and potential therapeutic target.

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 Raynaud's phenomenon.

Decrease in circulating dendritic cell precursors in patients with peripheral artery disease.

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. Inflammation is important for initiation and progression of the disease. Dendritic cells (DCs) as antigen-presenting cells play an important role in the immune system. Therefore, we hypothesize that, in patients with PAD, DCPs might be reduced in blood due to their recruitment into the vascular wall and induce a proinflammatory response. The numbers of myeloid DCPs, plasmacytoid DCPs, and total DCPs were analyzed by flow cytometry in blood of patients with PAD (n = 52) compared to controls (n = 60). Femoralis plaques (n = 12) of patients who underwent surgery were immunostained for CD209 and CD83 (mDCs) as well as CD304, CD123 (pDCs), and HLA-DR. In patients with PAD, a significant decrease in mDCPs, pDCPs, and tDCPs was observed. In immunostaining, markers indicative for mDCs (CD209: 16 versus 8 cells/0.1 mm(2), P = 0.02; CD83: 19 versus 5 cells/0.1 mm(2), P = 0.03) were significantly elevated in femoralis plaques compared to control vessels. We show for the first time that mDCPs, pDCPs, and tDCPs are significantly reduced in patients with PAD. Immunohistochemical analysis unraveled that the decrease in DCPs might be due to their recruitment into atherosclerotic plaques.

Investigation of bacterial translocation in chronic ischemic heart failure in the rat.

BACKGROUND: Increased markers of systemic inflammation had been found in patients with acute heart failure. These and other findings led to the hypothesis of an increased rate of bacterial translocation in severe or acute heart failure, leading to systemic inflammation. The present study examined if bacterial translocation occurs under physiological conditions in rats and if its rate and spectrum changes in chronic compensated ischemic heart failure. METHODS: Myocardial infarction (MI) was induced by proximal ligation of the left anterior descending coronary artery or a sham operation was performed. Rats were followed up for six months and mesenteric lymph nodes of the surviving animals with large MI were excised and bacterial translocation was quantified by cultivating viable bacteria. RESULTS: Induction of a large MI led to a significant cardiac remodelling, elevated levels of atrial natriuretic peptide, and pulmonary oedema. There was no difference in the spectrum or in the rate of bacterial translocation compared with controls, neither comparing all cultured bacteria nor predefined subgroups (e.g., intestinal bacteria). CONCLUSIONS: Bacterial translocation is a physiological process with no gradual increase in chronic compensated heart failure in rats.

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.

Late onset oral treatment with tranilast following large myocardial infarction has no beneficial effects on cardiac remodeling and mortality in rats.

Tranilast (Tra) reduces intracardiac interstitial fibrosis in the animal models of hypertensive heart failure and diabetic cardiomyopathy by inhibiting cardiac fibroblasts. The present study examined whether Tra has long-term effects on the cardiac remodeling in the remote area of the left ventricle (LV) following myocardial infarction (MI) in the rat. Treatment with Tra (n=40; 150 mg/kg twice daily) or placebo (Plac, n=36) was started at day 28 after induction of a large MI or sham-operation (ShO, n=18) in female Lewis rats. Collagen content was determined using high-performance liquid chromatography. Large MI led to a significant hypertrophy of the two ventricles, a severe dilatation of the LV and a shift of the chamber stiffness variables in the pressure volume curves. The six-month survival rates were Tra, 62.5%; Plac, 75%; and ShO, 100%. No significant difference was identified between Tra and Plac regarding survival rate and collagen content. Treatment with the anti-inflammatory and antifibrotic drug, Tra, started four weeks after the induction of a large MI in the rat, did not attenuate or positively influence remodeling in chronic ischemic heart failure and survival. Further studies are required to explore the effects of Tra on cardiac myocytes post-MI in more detail.

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/m(2); 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 (R(2) = -0.32, p = 0.001) and NYHA status (R(2) = 0.28, p = 0.001) and correlated with cardiorespiratory capacity (R(2) = 0.26, p = 0.03). CONCLUSION: Testosterone deficiency is frequent in male patients with CHF but does not appear to impact the regenerative EPCs.

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.

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.

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.

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

OBJECTIVE: Agreement 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 METHODS: Forty-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). RESULTS: Gadofosveset 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%). CONCLUSION: This 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.