Gadolinium Enhanced MR Coronary Vessel Wall Imaging at 3.0 Tesla.

Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD). Materials and Methods. Four healthy subjects (4 men, mean age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA). Results. LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced. Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30-45 minutes after administration of the contrast agent.

Spondylarthropathies in children--are they different from those in adults?

Juvenile spondylarthropathies (JSpAs) comprise a group of rheumatic diseases distinct from other categories of juvenile arthritis. Several classification systems have been applied, and some are specific for children, such as the seronegative enthesopathy and arthropathy (SEA) syndrome and the enthesitis-related arthritis, diagnostic forms in the International League of Associations for Rheumatism (ILAR) classification. JSpA seems more frequent than was previously believed, but actual epidemiological data show important variations between studies. Compared to adult patients, children with JSpA present with peripheral arthritis and enthesitis early in disease but sacroiliac and spine joints involvement many years later. A multidisciplinary team in a paediatric environment should be responsible for the management of children with spondylarthropathies to ensure the best care for these children with their chronic disease and risk of long-term disability. Recent advances in the treatment of rheumatic diseases with biological agents show promising results in children with JSpA. Further research needs to be conducted to increase our knowledge of the long-term outcome of these patients, to improve management, and to prevent long-term consequences of the disease.

Cost evaluation of cardiac magnetic resonance imaging versus coronary angiography for the work-up of coronary artery disease

Background: CMR has recently emerged as a robust and reliable technique to assess coronary artery disease (CAD). A negative perfusion CMR test predicts low event rates of 0.3-0.5%/year. Invasive coronary angiography (CA) remains the "gold standard" for the evaluation of CAD in many countries.Objective: Assessing the costs of the two strategies in the European CMR registry for the work-up of known or suspected CAD from a health care payer perspective. Strategy 1) a CA to all patients or 2) a CA only to patients who are diagnosed positive for ischemia in a prior CMR.Method and results: Using data of the European CMR registry (20 hospitals, 11'040 consecutive patients) we calculated the proportion of patients who were diagnosed positive (20.6%), uncertain (6.5%), and negative (72.9%) after the CMR test in patients with known or suspected CAD (n=2'717). No other medical test was performed to patients who were negative for ischemia. Positive diagnosed patients had a coronary angiography. Those with uncertain diagnosis had additional tests (84.7%: stress echocardiography, 13.1%: CCT, 2.3% SPECT), these costs were added to the CMR strategy costs. Information from costs for tests in Germany and Switzerland were used. A sensibility analysis was performed for inpatient CA. For costs see figure. Results - costs.Discussion: The CMR strategy costs less than the CA strategy for the health insurance systems both, in Germany and Switzerland. While lower in costs, the CMR strategy is a non-invasive one, does not expose to radiation, and yields additional information on cardiac function, viability, valves, and great vessels. Developing the use of CMR instead of CA might imply some reduction in costs together with superior patient safety and comfort, and a better utilization of resources at the hospital level. Document introduit le : 01.12.2011

Altering in vivo fate of heart-infiltrating progenitors from pro-fibrotic into F4/80+macrophages prevents progression of myocarditis into inflammatory dilated cardiomyopathy

Rationale: Experimental autoimmune myocarditis (EAM) mirrors important pathogenic aspects of inflammatory cardiomyopathy, a common cause of heart failure. In EAM, TGF-β-dependent conversion of heart-infiltrating prominin-1+ progenitors into myofibroblasts is critical for development of fibrosis and the end-stage heart failure phenotype. Therapeutic strategies modulating the in vivo fate of prominin-1+ progenitors might therefore prevent TGF-β-mediated cardiac fibrosis and pathological remodelling. Methods and Results: EAM was induced in BALB/c mice using alpha-myosin heavy chain (aMyHC) peptide/complete Freund's adjuvant (CFA) immunization. Prominin-1+ cells were isolated from the inflamed hearts at day 21 after immunization, expanded and treated with Macrophage Colony-Stimulating Factor (M-CSF) or Transforming Growth Factor-beta (TGF-β). Herein, we demonstrated that M-CSF turns, ex vivo and in the EAM, heart-infiltrating prominin-1+ progenitors into immunosuppressive F4/80/CD11b/CD16/32/NOS2-expressing, nitric oxide producing and E.coli bacteria phygocyting macrophages, and protect further TGF-β-stimulated differentiation into pathogenic myofibroblasts. Systemic M-CSF treatment during myocarditis completely prevented post-inflammatory fibrosis, T cell relapse and left ventricular dysfunction. Mechanistically, M-CSF-induced macrophage differentiation from prominin-1+ progenitors critically required nitric oxide synthase 2. Accordingly, M-CSF treatment failed to reduce myocardial fibrosis development in Nos2-/- mice. Conclusions: Altering the in vivo fate of inflammatory prominin-1 expressing progenitors from pro-fibrotic into the F4/80 expressing macrophage phenotype protects from myocarditis progression, cardiac fibrosis, and heart failure. These findings offer a modern therapeutic model and challenge former concepts, which attributed macrophages a detrimental role in inflammatory cardiomyopathy progression.

Eligibility for statin therapy in primary prevention: discrepancies using different guidelines in a population-based study in Switzerland

Introduction: Recommendations for statin use for primary prevention of coronary heart disease (CHD) are based on estimation of the 10-year CHD risk. We compared the 10-year CHD risk assessments and eligibility percentages for statin therapy using three scoring algorithms currently used in Switzerland. Methods: We studied 5683 women and men, aged 35-75, without overt cardiovascular disease (CVD), in a population-based study in Lausanne, Switzerland. We compared the 10-year CHD risk using three scoring schemes, i.e., the Framingham risk score (FRS) from the U.S. National Cholesterol Education Program's Adult Treatment Panel III (ATP III), the PROCAM scoring scheme from the International Atherosclerosis Society (IAS), and the European risk SCORE for low-risk countries, without and with extrapolation to 60 years as recommended by the European Society of Cardiology guidelines (ESC). With FRS and PROCAM, high-risk was defined as a 10-year risk of fatal or non-fatal CHD >20% and a 10-year risk of fatal CVD >= 5% with SCORE. We compared the proportions of high-risk participants and eligibility for statin use according to these three schemes. For each guideline, we estimated the impact of increased statin use from current partial compliance to full compliance on potential CHD deaths averted over 10 years, using a success proportion of 27% for statins. Results: Participants classified at high-risk (both genders) were 5.8% according to FRS and 3.0% to the PROCAM, whereas the European risk SCORE classified 12.5% at high-risk (15.4% with extrapolation to 60 years). For the primary prevention of CHD, 18.5% of participants were eligible for statin therapy using ATP III, 16.6% using IAS, and 10.3% using ESC (13.0% with extrapolation) because ESC guidelines recommend statin therapy only in high-risk subjects. In comparison with IAS, agreement to identify eligible adults for statins was good with ATP III, but moderate with ESC (Figure). Using a population perspective, a full compliance with ATP III guidelines would reduce up to 17.9% of the 24'310 CHD deaths expected over 10 years in Switzerland, 17.3% with IAS and 10.8% with ESC (11.5% with extrapolation). Conclusion: Full compliance with guidelines for statin therapy would result in substantial health benefits, but proportions of high-risk adults and eligible adults for statin use varied substantially depending on the scoring systems and corresponding guidelines used for estimating CHD risk in Switzerland.

Coronary magnetic resonance angiography.

Despite advances in both prevention and treatment, cardiovascular disease remains the leading cause of morbidity and mortality in the United States. The current gold standard for the diagnosis of coronary artery disease is the x-ray coronary angiogram, which is both costly and associated with a small risk of morbidity. More than 1 million Americans are referred for this test annually, and despite the availability of numerous noninvasive tests to identify patients with coronary artery disease, > or =35% of patients referred for this test are found not to have disease. It therefore would be beneficial to use a noninvasive test to allow the presence of coronary atherosclerosis to be determined directly. Coronary magnetic resonance angiography, a technique that is aimed at establishing a noninvasive test for the assessment of significant coronary stenoses, obviates the risks of patient exposure to radiation of x-ray angiography and therefore represents a major step forward in diagnostic cardiology.

IRM cardiaque dans le suivi des cardiopathies congénitales à l'âge adulte [Cardiac MRI in the follow-up of adult congenital cardiomyopathy patients].

Magnetic resonance imaging is a rapidly developing modality in cardiology. It offers an excellent image definition and a large field of view, allowing a more accurate morphological assessment of cardiac malformations. Due to its unique versatility and its ability to provide myocardial tissue characterization, cardiac magnetic resonance (CMR) is now recognized as a central imaging modality for a wide range of congenital heart diseases, including assessment of post-surgical cardiac anatomy, quantification of valvular disease and detection of myocardial ischemia. CMR provides useful diagnostic information without any radiation exposure, and improves the global management of patients with congenital heart disease.

Double-oblique free-breathing high resolution three-dimensional coronary magnetic resonance angiography.

OBJECTIVES: The goal of the present study was to develop a strategy for three-dimensional (3D) volume acquisition along the major axes of the coronary arteries. BACKGROUND: For high-resolution 3D free-breathing coronary magnetic resonance angiography (MRA), coverage of the coronary artery tree may be limited due to excessive measurement times associated with large volume acquisitions. Planning the 3D volume along the major axis of the coronary vessels may help to overcome such limitations. METHODS: Fifteen healthy adult volunteers and seven patients with X-ray angiographically confirmed coronary artery disease underwent free-breathing navigator-gated and corrected 3D coronary MRA. For an accurate volume targeting of the high resolution scans, a three-point planscan software tool was applied. RESULTS: The average length of contiguously visualized left main and left anterior descending coronary artery was 81.8 +/- 13.9 mm in the healthy volunteers and 76.2 +/- 16.5 mm in the patients (p = NS). For the right coronary artery, a total length of 111.7 +/- 27.7 mm was found in the healthy volunteers and 79.3 +/- 4.6 mm in the patients (p = NS). Comparing coronary MRA and X-ray angiography, a good agreement of anatomy and pathology was found in the patients. CONCLUSIONS: Double-oblique submillimeter free-breathing coronary MRA allows depiction of extensive parts of the native coronary arteries. The results obtained in patients suggest that the method has the potential to be applied in broader prospective multicenter studies where coronary MRA is compared with X-ray angiography.

Le rein de l'enfant face à la chimiothérapie [The kidney in children under chemotherapy].

Nowadays more and more children survive after an intensive anti-tumoral therapy. The price to pay consists of numerous and relatively frequent long-term sequelae (secondary tumors, neuropsychological deficits, endocrine or cardiac damage). After chemotherapy, we sometimes observe renal side-effects, either tubular (metabolic acidosis, hypokalemia, hypomagnesemia, proteinuria, Fanconi syndrome, rickets) or glomerular (acute or chronic decreased GFR). These renal toxic side-effects are encountered especially after cisplatinum and ifosfamide, less frequently after carboplatin and cyclophosphamide. The pediatrician has to be aware of these toxic nephrologic side-effects, to look out for them and monitor carefully the renal function of all paediatric patients receiving these potentially nephrotoxic chemotherapies.

Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using "positive contrast" magnetic resonance imaging.

OBJECTIVES: This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]). BACKGROUND: The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility. METHODS: Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mumol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days. RESULTS: After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis. CONCLUSIONS: Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques.

Endothelial nitric oxide synthase gene transfer restores endothelium-dependent relaxations and attenuates lesion formation in carotid arteries in apolipoprotein E-deficient mice.

Nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1) exert partly opposing effects in vascular biology. NO plays pleiotropic vasoprotective roles including vasodilation and inhibition of platelet aggregation, smooth muscle cell proliferation, and endothelial monocyte adhesion, the last effect being mediated by MCP-1 downregulation. Early stages of arteriosclerosis are associated with reduced NO bioactivity and enhanced MCP-1 expression. We have evaluated adenovirus-mediated gene transfer of human endothelial NO synthase (eNOS) and of a N-terminal deletion (8ND) mutant of the MCP-1 gene that acts as a MCP-1 inhibitor in arteriosclerosis-prone, apolipoprotein E-deficient (ApoE(-/-)) mice. Endothelium-dependent relaxations were impaired in carotid arteries instilled with a noncoding adenoviral vector but were restored by eNOS gene transfer (p < 0.01). A perivascular collar was placed around the common carotid artery to accelerate lesion formation. eNOS gene transfer reduced lesion surface areas, intima/media ratios, and macrophage contents in the media at 5-week follow-up (p < 0.05). In contrast, 8ND-MCP-1 gene transfer did not prevent lesion formation. In conclusion, eNOS gene transfer restores endothelium-dependent vasodilation and inhibits lesion formation in ApoE(-/-) mouse carotids. Further studies are needed to assess whether vasoprotection is maintained at later disease stages and to evaluate the long-term efficacy of eNOS gene therapy for primary arteriosclerosis.