BACKGROUNDIn patients with stable angina, two strategies are often used to guide revascularization: one involves myocardial-perfusion cardiovascular magnetic resonance imaging (MRI), and the other involves invasive angiography and measurement of fractional flow reserve (FFR). Whether a cardiovascular MRI-based strategy is noninferior to an FFRbased strategy with respect to major adverse cardiac events has not been established. METHODSWe performed an unblinded, multicenter, clinical-effectiveness trial by randomly assigning 918 patients with typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test to a cardiovascular MRI-based strategy or an FFR-based strategy. Revascularization was recommended for patients in the cardiovascular-MRI group with ischemia in at least 6% of the myocardium or in the FFR group with an FFR of 0.8 or less. The composite primary outcome was death, nonfatal myocardial infarction, or target-vessel revascularization within 1 year. The noninferiority margin was a risk difference of 6 percentage points. RESULTSA total of 184 of 454 patients (40.5%) in the cardiovascular-MRI group and 213 of 464 patients (45.9%) in the FFR group met criteria to recommend revascularization (P = 0.11). Fewer patients in the cardiovascular-MRI group than in the FFR group underwent index revascularization (162 [35.7%] vs. 209 [45.0%], P = 0.005). The primary outcome occurred in 15 of 421 patients (3.6%) in the cardiovascular-MRI group and 16 of 430 patients (3.7%) in the FFR group (risk difference, −0.2 percentage points; 95% confidence interval, −2.7 to 2.4), findings that met the noninferiority threshold. The percentage of patients free from angina at 12 months did not differ significantly between the two groups (49.2% in the cardiovascular-MRI group and 43.8% in the FFR group, P = 0.21). CONCLUSIONSAmong patients with stable angina and risk factors for coronary artery disease, myocardial-perfusion cardiovascular MRI was associated with a lower incidence of coronary revascularization than FFR and was noninferior to FFR with respect to major adverse cardiac events.

AimMarfan syndrome (MFS) is an inherited connective tissue disease which frequently involves the cardiovascular system. The heart can be affected since valvular regurgitation is a common complication. However, there is still debate whether a primary cardiomyopathy exists. Our aim was to evaluate the existence of a Marfan-related cardiomyopathy using cardiovascular magnetic resonance. Methods and resultsWe retrospectively evaluated 68 consecutive adult patients with no cardiovascular surgery or significant valvular regurgitation. Left ventricular and right ventricular volumes, ejection fraction, and mass were estimated and compared with published data on a healthy control population. Patients were also assessed for heart failure, aortic dimensions, and valve disease.One quarter (25.0%) of Marfan patients had reduced left ventricular ejection fraction (LVEF), with 25.0% having increased left ventricular end-diastolic and 30.8% having increased end-systolic volumes. The right ventricular ejection fraction was reduced in 10.3%, with increased right ventricular end-diastolic volumes in 11.8% and increased end-systolic volumes in 13.2%. On univariate analysis, no association was found between reduced LVEF and age, gender, indexed aortic dimensions, presence of mitral valve prolapse, or valve regurgitation. ConclusionThis study supports the existence of a primary cardiomyopathy in a subgroup of Marfan patients. The biventricular enlargement and dysfunction is usually mild, asymptomatic, and independent from other cardiovascular manifestations. Further studies are needed to assess underlying causes and natural history of this condition. Routine monitoring and treatment in MFS may need to be tailored not only to prevent aortic root expansion but also to support myocardial function.--

BackgroundThe aetiology and clinical significance of troponin release following endurance exercise is unclear but may be due to transient myocardial inflammation. Cardiovascular magnetic resonance (CMR) affords us the opportunity to evaluate the presence of myocardial inflammation and focal fibrosis and is the ideal imaging modality to study this hypothesis. We sought to correlate the relationship between acute bouts of ultra endurance exercise leading to cardiac biomarkers elevation and the presence of myocardial inflammation and fibrosis using CMR.Methods17 recreation athletes (33.5 +/- 6.5 years) were studied before and after a marathon run with troponin, NTproBNP, and CMR. Specific imaging parameters to look for inflammation included T2 weighted images, and T1 weighted spin-echo images before and after an intravenous gadolinium-DTPA to detect myocardial hyperemia secondary to inflammation. Late gadolinium imaging was performed (LGE) to detect any focal regions of replacement fibrosis.ResultsEleven of the 17 participant had elevations of TnI above levels of cut off for myocardial infarction 6 hrs after the marathon (0.075 +/- 0.02, p = 0.007). Left ventricular volumes were reduced post marathon and a small increase in ejection fraction was noted (64+/- 1% pre, 67+/- 1.2% post, P = 0.014). Right ventricular volumes, stroke volume, and ejection fraction were unchanged post marathon. No athlete fulfilled criteria for myocardial inflammation based on current criteria. No regions of focal fibrosis were seen in any of the participants.ConclusionExercise induced cardiac biomarker release is not associated with any functional changes by CMR or any detectable myocardial inflammation or fibrosis.

The understanding of the induction and regulation of inducible nitric-oxide synthase (iNOS) in human cells may be important in developing therapeutic interventions for inflammatory diseases. In the present study, we not only demonstrated that human fetal mixed glial cultures, as well as enriched microglial cultures, synthesize iNOS and nitric oxide (NO) in response to cytokine stimulation, but also assessed the kinetics of iNOS and NO synthesis in human fetal mixed glial cultures. The iNOS mRNA was expressed within 2 h after stimulation and decreased to base line by 2 days. Significant levels of iNOS protein appeared within 24 h after stimulation and remained elevated during the culture period. A dramatic increase in NO production and NO-mediated events, such as the induction of cyclic guanosine monophosphate (cGMP), NADPH diaphorase activity, and nitrotyrosine occurred 3 days after stimulation, a delay of 48 h from the time of the first expression of iNOS enzyme. This delay of NO production was altered by the addition of tetrahydrobiopterin, but not by the addition of L-arginine, heme, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), or NADPH. These findings suggest that a post-translational regulatory event might be involved in iNOS-mediated NO production in human glia.Nitric oxide (NO) mediates functions as diverse as vasodilation (1-3), neurotransmission (4, 5), and immune-mediated cytotoxicity (6 -8). NO production is catalyzed by NO synthases of which there are three isoforms (9 -11). Multiple sclerosis (MS) 1 is a central nervous system disorder with immune-mediated destruction of myelin and the myelin-producing cells, oligodendrocytes. The presence of inducible nitric-oxide synthase (iNOS or Type II NOS) and the "footprints" of NO in tissues of patients with MS and animals with experimental allergic encephalomyelitis, a model for MS, suggests that NO may play a role in this central nervous system autoimmune disease (12-15). Glial cells including astrocytes, microglia, and oligodendrocytes are all involved in the lesion and plaque formation in MS and experimental allergic encephalomyelitis. Rodent astrocytes and microglia express high levels of Type II/iNOS and release significant NO within hours after lipopolysaccharide stimulation in vitro (8,16,17). In culture NO produces mitochondrial dysfunction, DNA damage, morphological changes, and necrotic cell death in rat oligodendrocytes (8, 18), while rat astrocytes and microglia are more resistant to NO-mediated damage (19,20). If such glial cell-mediated NO-dependent damages were to occur in vivo in MS, it could contribute to the plaque formation and a loss of myelin.Since MS is a human central nervous system disorder, insights into the role of NO in the immnopathology of MS require a better understanding of NO induction in human glial cells. However, the induction and the regulation of iNOS in human glial cells is still unclear and seems substantially different from that in rodents. First of all, the nature of inducing signals is different...