De la recommandation d'un dépistage à son (non) implantation: le cas de l'anévrisme de l'aorte abdominale. [From guidelines for screening to their (poor) implementation: the case of the abdominal aortic aneurysm].

Suite à des essais cliniques randomisés démontrant l'efficacité du dépistage de l'anévrisme de l'aorte abdominale (AAA) par échographie, plusieurs recommandations ont été publiées dans de nombreux pays en faveur du dépistage dans une partie de la population générale. De plus, au-delà de la rupture aortique, le dépistage d'un petit AAA semble être une bonne occasion d'appliquer les stratégies de prévention secondaire, permettant une amélioration globale du pronostic cardiovasculaire du patient. Ces recommandations sont cependant peu suivies; les campagnes de dépistage systématique sont rares, laissant la responsabilité du dépistage au médecin généraliste. Cet article se propose de discuter les raisons de la non-implantation du dépistage de l'AAA. [Abstract] Following the evidence of benefits of ultrasound screening for abdominal aorta aneurysms (AAA), several guidelines support this screening in population. Beyond the prompt diagnosis of AAA prior to its rupture of grim vital prognosis, small AAA can beconsidered as a prognostic marker for cardiovascular diseases (CVD). Yet, its detection is an opportunity for secondary prevention to reduce CVD mortality. Despite, these guidelines are poorly applied: systematic screening campaigns are infrequent, making the screening of family physicians responsibility. While the major benefit from this screening strategy is to reduce AAA-related death (but only trivial effect on long-term total mortality), this explains only partially the lack of guidelines implementation. The reasons of the poor implementation of these guidelines are discussed herein.

Renal arteries: navigator-gated balanced fast field-echo projection MR angiography with aortic spin labeling: initial experience.

A cardiac-triggered free-breathing three-dimensional balanced fast field-echo projection magnetic resonance (MR) angiographic sequence with a two-dimensional pencil-beam aortic labeling pulse was developed for the renal arteries. For data acquisition during free breathing in eight healthy adults and seven consecutive patients with renal artery disease, real-time navigator technology was implemented. This technique allows high-spatial-resolution and high-contrast renal MR angiography and visualization of renal artery stenosis without exogenous contrast agent or breath hold. Initial promising results warrant larger clinical studies.

Involvement of gap junctional intercellular communication in the pathophysiology of inflammation

SUMMARY Inflammation has evolved as a mechanism to defend the body against invading microorganisms and to respond to injury. It requires the coordinated response of a large number of cell types from the whole organism in a time- and space-dependent fashion. This coordination involves several cell-cell communication mechanisms. Exchange of humoral mediators such as cytokines is a major one. Moreover, direct contact between cells happens and plays a primordial role, for example when macrophages present antigens to lymphocytes. Contact between endothelial cells and leucocytes occurs when the latter cross the blood vessel barrier and transmigrate to the inflammatory site. A particular way by which cells communicate with each other in the course of inflammation, which at this time starts to gain attention, is the intercellular communication mediated by gap junctions. Gap junctions are channels providing a direct pathway (i.e. without transit through the extracellular space) for the diffusion of small molecules between adjacent cells. This process is known as gap junctional intercellular communication (GJIC). The general aim of this thesis was to study a possible involvement of GJIC in the pathophysiology of inflammation. A first part of the work was dedicated to study the implication of GJIC in the modification of vascular endothelial function by inflammation. In a second part, we were interested in the possible role of GJIC in the transmigration of neutrophil polymorphonuclear leucocytes through the endothelium. The main positive finding of this work is that acute inflammation preferentially modulates the expression of connexin 40 (Cx40), a gap junction protein specifically expressed in vascular endothelium. The modulation could be towards overexpression (aortic endothelium of septic rats) or towards downregulation (acutely inflamed mouse lung). We put a lot of efforts in search of possible functions of these modulations, in two directions: a potential protective role of Cx40 increased expression against sepsis-induced endothelial dysfunction, and a facilitating role of Cx40 decreased expression in neutrophil transmigration. To pursue both directions, it seemed logical to study the impact of Cx40 deletion using knock-out mice. Concerning the potential protective role of Cx40 overexpression we encountered a roadblock as we observed, in the aorta, a Cx40 downregulation in wild type mouse whereas Cx40 was upregulated in the rat. Regarding the second direction and using an in vivo approach, we observed that pulmonary neutrophil transmigration was not affected by the genetic deletion of Cx40. In spite of their negative nature, these results are the very first ones regarding the potential implication of GJIC concerning leucocyte transmigration in vivo. Because this process involves such tight cell-cell physical contacts, the hypothesis for a role of GJIC remains attractive.

A fast 3D approach for coronary MRA.

Two-dimensional (2D)-breath-hold coronary magnetic resonance angiography (MRA) has been shown to be a fast and reliable method to depict the proximal coronary arteries. Recent developments, however, allow for free-breathing navigator gated and navigator corrected three-dimensional (3D) coronary MRA. These 3D approaches have potential for improved signal-to-noise ratio (SNR) and allow for the acquisition of adjacent thin slices without the misregistration problems known from 2D approaches. Still, a major impediment of a 3D acquisition is the increased scan time. The purpose of this study was the implementation of a free-breathing navigator gated and corrected ultra-fast 3D coronary MRA technique, which allows for scan times of less than 5 minutes. Twelve healthy adult subjects were examined in the supine position using a navigator gated and corrected ECG triggered ultra-fast 3D interleaved gradient echo planar imaging sequence (TFE-EPI). A 3D slab, consisting of 20 slices with a reconstructed slice thickness of 1.5 mm, was acquired with free-breathing. The diastolic TFE-EPI acquisition block was preceded by a T2prep pre-pulse, a diaphragmatic navigator pulse, and a fat suppression pre-pulse. With a TR of 19 ms and an effective TE of 5.4 ms, the duration of the data acquisition window duration was 38 ms. The in-plane spatial resolution was 1.0-1.3 mm*1.5-1.9 mm. In all cases, the entire left main (LM) and extensive portions of the left anterior descending (LAD) and right coronary artery (RCA) could be visualized with an average scan time for the entire 3D-volume data set of 2:57 +/- 0:51 minutes. Average contiguous vessel length visualized was 53 +/- 11 mm (range: 42 to 75 mm) for the LAD and 84 +/- 14 mm (range: 62 to 112 mm) for the RCA. Contrast-to-noise between coronary blood and myocardium was 5.0 +/- 2.3 for the LM/LAD and 8.0 +/- 2.9 for the RCA, resulting in an excellent suppression of myocardium. We present a new approach for free-breathing 3D coronary MRA, which allows for scan times superior to corresponding 2D coronary MRA approaches, and which takes advantage of the enhanced SNR of 3D acquisitions and the post-processing benefits of thin adjacent slices. The robust image quality and the short average scanning time suggest that this approach may be useful for screening the major coronary arteries or identification of anomalous coronary arteries. J. Magn. Reson. Imaging 1999;10:821-825.

PET-measured responses of MBF to cold pressor testing correlate with indices of coronary vasomotion on quantitative coronary angiography.

The aims of this study were to determine whether responses in myocardial blood flow (MBF) to the cold pressor testing (CPT) method noninvasively with PET correlate with an established and validated index of flow-dependent coronary vasomotion on quantitative angiography. METHODS: Fifty-six patients (57 +/- 6 y; 16 with hypertension, 10 with hypercholesterolemia, 8 smokers, and 22 without coronary risk factors) with normal coronary angiograms were studied. Biplanar end-diastolic images of a selected proximal segment of the left anterior descending artery (LAD) (n = 27) or left circumflex artery (LCx) (n = 29) were evaluated with quantitative coronary angiography in order to determine the CPT-induced changes of epicardial luminal area (LA, mm(2)). Within 20 d of coronary angiography, MBF in the LAD, LCx, and right coronary artery territory was measured with (13)N-ammonia and PET at baseline and during CPT. RESULTS: CPT induced on both study days comparable percent changes in the rate x pressure product (%DeltaRPP, 37% +/- 13% and 40% +/- 17%; P = not significant [NS]). For the entire study group, the epicardial LA decreased from 5.07 +/- 1.02 to 4.88 +/- 1.04 mm(2) (DeltaLA, -0.20 +/- 0.89 mm(2)) or by -2.19% +/- 17%, while MBF in the corresponding epicardial vessel segment increased from 0.76 +/- 0.16 to 1.03 +/- 0.33 mL x min(-1) x g(-1) (DeltaMBF, 0.27 +/- 0.25 mL x min(-1) x g(-1)) or 36% +/- 31% (P <or= 0.0001). However, in normal controls without coronary risk factors (n = 22), the epicardial LA increased from 5.01 +/- 1.07 to 5.88 +/- 0.89 mm(2) (19.06% +/- 8.9%) and MBF increased from 0.77 +/- 0.16 to 1.34 +/- 0.34 mL x min(-1) x g(-1) (74.08% +/- 23.5%) during CPT, whereas patients with coronary risk factors (n = 34) revealed a decrease of epicardial LA from 5.13 +/- 1.48 to 4.24 +/- 1.12 mm(2) (-15.94% +/- 12.2%) and a diminished MBF increase (from 0.76 +/- 0.20 to 0.83 +/- 0.25 mL x min(-1) x g(-1) or 10.91% +/- 19.8%) as compared with controls (P < 0.0001, respectively), despite comparable changes in the RPP (P = NS). In addition, there was a significant correlation (r = 0.87; P <or= 0.0001) between CPT-related percent changes in LA on quantitative angiography and in MBF as measured with PET. CONCLUSION: The observed close correlation between an angiographically established parameter of flow-dependent and, most likely, endothelium-mediated coronary vasomotion and PET-measured MBF further supports the validity and value of MBF responses to CPT as a noninvasively available index of coronary circulatory function.

Physical training and hypertension have opposite effects on endothelial brain-derived neurotrophic factor expression.

AIMS: Changes in circulating brain-derived neurotrophic factor (BDNF) levels were reported in patients with or at risk for cardiovascular diseases associated with endothelial dysfunction, suggesting a link between BDNF and endothelial functionality. However, little is known on cardiovascular BDNF. Our aim was to investigate levels/localization, function, and relevance of cardiovascular BDNF. METHODS AND RESULTS: BDNF levels (western blotting) and localization (immunostaining) were assessed in the heart and aorta from rats with impaired (spontaneously hypertensive rats [SHR]), normal (Wistar Kyoto rats [WKY]), and improved (SHR and WKY subjected to physical training) endothelial function. BDNF levels were also measured in cultured endothelial cells (CECs) subjected to low and high shear stress. The cardiovascular effects of BDNF were investigated in isolated aortic rings and hearts. The results showed high BDNF levels in the heart and aorta, the expression being prominent in endothelial cells as compared with other cell types. Exogenous BDNF vasodilated aortic rings but changed neither coronary flow nor cardiac contractility. Hypertension was associated with decreased expression of BDNF in the endothelium, whereas physical training led to endothelial BDNF up-regulation not only in WKY but also in SHR. Exposure of CECs to high shear stress stimulated BDNF production and secretion. CONCLUSION: Cardiovascular BDNF is mainly localized within endothelial cells in which its expression is dependent on endothelial function. These results open new perspectives on the role of endothelial BDNF in cardiovascular health.

Fatty acid amide hydrolase deficiency enhances intraplaque neutrophil recruitment in atherosclerotic mice.

OBJECTIVE: Endocannabinoid levels are elevated in human and mouse atherosclerosis, but their causal role is not well understood. Therefore, we studied the involvement of fatty acid amide hydrolase (FAAH) deficiency, the major enzyme responsible for endocannabinoid anandamide degradation, in atherosclerotic plaque vulnerability. METHODS AND RESULTS: We assessed atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) and ApoE(-/-)FAAH(-/-) mice. Before and after 5, 10, and 15 weeks on high-cholesterol diet, we analyzed weight, serum cholesterol, and endocannabinoid levels, and atherosclerotic lesions in thoracoabdominal aortas and aortic sinuses. Serum levels of FAAH substrates anandamide, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) were 1.4- to 2-fold higher in case of FAAH deficiency. ApoE(-/-)FAAH(-/-) mice had smaller plaques with significantly lower content of smooth muscle cells, increased matrix metalloproteinase-9 expression, and neutrophil content. Circulating and bone marrow neutrophil counts were comparable between both genotypes, whereas CXC ligand1 levels were locally elevated in aortas of FAAH-deficient mice. We observed enhanced recruitment of neutrophils, but not monocytes, to large arteries of ApoE(-/-) mice treated with FAAH inhibitor URB597. Spleens of ApoE(-/-)FAAH(-/-) mice had reduced CD4+FoxP3+regulatory T-cell content, and in vitro stimulation of splenocytes revealed significantly elevated interferon-γ and tumor necrosis factor-α production in case of FAAH deficiency. CONCLUSIONS: Increased anandamide and related FAAH substrate levels are associated with the development of smaller atherosclerotic plaques with high neutrophil content, accompanied by an increased proinflammatory immune response.

Aortic arch atheroma and the risk of stroke.

Brain infarction of unknown cause, known as cryptogenic stroke, represents 30% to 40% of all ischemic strokes, or approximately 400,000 cases each year in western Europe. In this category of patients new potential causes, such as aortic arch atheroma in the elderly, have been investigated in the past two decades.

Citizens' preferences for brand name drugs for treating acute and chronic conditions: a pilot study.

Background: Generic drugs have been advocated to decrease the proportion of healthcare costs devoted to drugs, but are still underused. Objective: To assess citizens' preferences for brand name drugs (BNDs) compared with generic drugs for treating acute and chronic conditions. Methods: A questionnaire with eight hypothetical scenarios describing four acute and four chronic conditions was developed, with willingness to pay (WTP) determined using a payment card system randomized to ascending (AO) or descending order (DO) of prices. The questionnaire was distributed with an explanation sheet, an informed consent form and a pre-stamped envelope over a period of 3 weeks in 19 community pharmacies in Lausanne, Switzerland. The questionnaire was distributed to every third customer who also had health insurance, understood French and was aged =16 years (up to a maximum of ten customers per day and 100 per pharmacy). The main outcome measure was preferences assessed by WTP for BNDs as compared with generics, and impact of participants' characteristics on WTP. Results: Of the 1800 questionnaires, 991 were distributed and 393 returned (pharmacy participation rate?=?55%, subject participation rate?=?40%, overall response rate?=?22%); 51.7% were AO and 48.3% DO. Participants were predominantly women (62.6%) and of median age 62 years (range 16-90). The majority (70%) declared no WTP for BNDs as compared with generics. WTP was higher in people with an acute disease than in those with a chronic disease, did not depend on the type of chronic disease, and was higher in people from countries other than Switzerland. Conclusions: Most citizens visiting pharmacies attribute no added value to BNDs as compared with generics, although some citizen characteristics affected WTP. These results could be of interest to several categories of decision makers within the healthcare system.

Performance of a new gadolinium-based intravascular contrast agent in free-breathing inversion-recovery 3D coronary MRA.

In three-dimensional (3D) coronary magnetic resonance angiography (MRA), the in-flow contrast between the coronary blood and the surrounding myocardium is attenuated as compared to thin-slab two-dimensional (2D) techniques. The application of a gadolinium (Gd)-based intravascular contrast agent may provide an additional source of signal and contrast by reducing T(1blood) and supporting the visualization of more distal or branching segments of the coronary arterial tree. In six healthy adults, the left coronary artery (LCA) system was imaged pre- and postcontrast with a 0.075-mmol/kg bodyweight dose of the intravascular contrast agent B-22956. For imaging, an optimized free-breathing, navigator-gated and -corrected 3D inversion recovery (IR) sequence was used. For comparison, state-of-the-art baseline 3D coronary MRA with T(2) preparation for non-exogenous contrast enhancement was acquired. The combination of IR 3D coronary MRA, sophisticated navigator technology, and B-22956 allowed for an extensive visualization of the LCA system. Postcontrast, a significant increase in both the signal-to-noise ratio (SNR; 46%, P < 0.05) and contrast-to-noise ratio (CNR; 160%, P < 0.01) was observed, while vessel sharpness of the left anterior descending (LAD) artery and the left coronary circumflex (LCX) were improved by 20% (P < 0.05) and 18% (P < 0.05), respectively.

Does altering inclination alter effectiveness of treadmill training for gait impairment after stroke? A randomized controlled trial.

Objective: To assess whether a downhill walking training programme is more effective than the same amount of training applied uphill in chronic stroke survivors. Design: Randomized, single-blind study. Setting: Outpatient rehabilitation service. Methods: Thirty-eight adults with hemiplegia from stroke lasting more than three months were randomly allocated to one of the two groups: 'UP' - 45 minutes of physical therapy + 30 minutes of treadmill with 5% ascending slope; and 'DOWN' - 45 minutes of physical therapy + 30 minutes of treadmill with 5% descending slope. Both groups were treated 5 times a week for six weeks. Patients were evaluated before treatment, at the end of treatment and after three months. Outcome measures: Primary outcome measure was the number of patients showing an improvement in 6-minute walking test (6MWT) greater than 50 m. Secondary outcome measures were: (1) number of patients showing a clinically relevant improvement of gait speed during 10-m walking test (10mWT); (2) number of patients showing an improvement in timed up and go (TUG) greater than minimal detectable change. Results: Both groups had a significant improvement after treatment and at follow-up. At the end of treatment, compared to UP group, more patients in the DOWN group showed clinically significant improvements in primary and secondary outcomes (16/19 patients for 6MWT, 11/19 patients for 10mWT and 9/19 patients for TUG compared with 3/19, 4/19 and 2/19 patients, respectively, P < 0.01). At follow-up, results were similar except for 10mWT. Conclusions: In chronic stroke patients, downhill treadmill training produces a bigger effect than uphill training.

Successful combined minimally invasive direct coronary artery bypass and transapical aortic valve implantation.

Transapical aortic valve implantation is indicated in high-risk patients with aortic stenosis and peripheral vascular disease requiring aortic valve replacement. Minimally invasive direct coronary artery bypass grafting is also a valid, minimally invasive option for myocardial revascularization in patients with critical stenosis on the anterior descending coronary artery. Both procedures are performed through a left minithoracotomy, without cardiopulmonary bypass, aortic cross-clamping, and cardioplegic arrest. We describe a successful combined transapical aortic valve implantation and minimally invasive direct coronary bypass in a high-risk patient with left anterior descending coronary artery occlusion and severe aortic valve stenosis.

Flow targeted 3D steady-state free-precession coronary MR angiography: comparison of three different imaging approaches.

PURPOSE: To compare 3 different flow targeted magnetization preparation strategies for coronary MR angiography (cMRA), which allow selective visualization of the vessel lumen. MATERIAL AND METHODS: The right coronary artery of 10 healthy subjects was investigated on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Healthcare, Best, NL). A navigator-gated and ECG-triggered 3D radial steady-state free-precession (SSFP) cMRA sequence with 3 different magnetization preparation schemes was performed referred to as projection SSFP (selective labeling of the aorta, subtraction of 2 data sets), LoReIn SSFP (double-inversion preparation, selective labeling of the aorta, 1 data set), and inflow SSFP (inversion preparation, selective labeling of the coronary artery, 1 data set). Signal-to-noise ratio (SNR) of the coronary artery and aorta, contrast-to-noise ratio (CNR) between the coronary artery and epicardial fat, vessel length and vessel sharpness were analyzed. RESULTS: All cMRA sequences were successfully obtained in all subjects. Both projection SSFP and LoReIn SSFP allowed for selective visualization of the coronary arteries with excellent background suppression. Scan time was doubled in projection SSFP because of the need for subtraction of 2 data sets. In inflow SSFP, background suppression was limited to the tissue included in the inversion volume. Projection SSFP (SNR(coro): 25.6 +/- 12.1; SNR(ao): 26.1 +/- 16.8; CNR(coro-fat): 22.0 +/- 11.7) and inflow SSFP (SNR(coro): 27.9 +/- 5.4; SNR(ao): 37.4 +/- 9.2; CNR(coro-fat): 24.9 +/- 4.8) yielded significantly increased SNR and CNR compared with LoReIn SSFP (SNR(coro): 12.3 +/- 5.4; SNR(ao): 11.8 +/- 5.8; CNR(coro-fat): 9.8 +/- 5.5; P &lt; 0.05 for both). Longest visible vessel length was found with projection SSFP (79.5 mm +/- 18.9; P &lt; 0.05 vs. LoReIn) whereas vessel sharpness was best in inflow SSFP (68.2% +/- 4.5%; P &lt; 0.05 vs. LoReIn). Consistently good image quality was achieved using inflow SSFP likely because of the simple planning procedure and short scanning time. CONCLUSION: Three flow targeted cMRA approaches are presented, which provide selective visualization of the coronary vessel lumen and in addition blood flow information without the need of contrast agent administration. Inflow SSFP yielded highest SNR, CNR and vessel sharpness and may prove useful as a fast and efficient approach for assessing proximal and mid vessel coronary blood flow, whereas requiring less planning skills than projection SSFP or LoReIn SSFP.