Philippe Cluzel

Is 18F‐fluorodeoxyglucose positron emission tomography scanning a reliable way to assess disease activity in takayasu arteritis?

OBJECTIVEn(18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning has been proposed as a new way of assessing disease activity in Takayasu arteritis (TA), but previous studies have used the nonvalidated National Institutes of Health (NIH) global activity criteria, and thus might be biased. This study was undertaken to determine the value of PET scanning for assessment of disease activity in TA, by comparing PET scan data with clinical, biologic, and magnetic resonance imaging (MRI) data assessed separately.nnnMETHODSnTwenty-eight patients with TA (according to the American College of Rheumatology criteria) underwent a total of 40 PET scans. Images were reviewed by 2 pairs of independent nuclear medicine physicians and assessed for pattern and intensity of vascular uptake. TA activity data were obtained within 15 days of the PET scans.nnnRESULTSnPET scanning revealed abnormal vascular uptake in 47% of the 40 examinations. The uptake intensity grade was 0 in 7 scans, grade 1 in 7 scans, grade 2 in 13 scans, and grade 3 in 13 scans. Morphologic analysis was conducted by grading the pattern of the vascular uptake as diffuse (73%), segmental (20%), or focal (13%). There was a trend toward an association between clinically active disease and the semiquantitative assessment of FDG uptake (P = 0.08). We found no statistical association between levels of acute-phase reactants and intensity of uptake. There was no significant association between the semiquantitative assessment of FDG uptake and the presence of vascular wall thickening (P = 0.23), gadolinium uptake (P = 0.73), or the presence of vascular wall edema (P = 0.56).nnnCONCLUSIONnOur findings indicate that there is no association between FDG vascular uptake intensity and clinical, biologic, or MRI assessment of disease activity. Previous studies using the nonvalidated NIH global activity criteria are likely biased.

18F-Fluorodeoxyglucose―Positron Emission Tomography Scanning Is More Useful in Followup Than in the Initial Assessment of Patients With Erdheim-Chester Disease

OBJECTIVEnErdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. The aim of this study was to assess the value of whole-body scanning with (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in a large cohort of ECD patients from a single center.nnnMETHODSnWe retrospectively reviewed all PET scans performed on 31 patients with ECD who were referred to our department between 2005 and 2008. PET images were reviewed by 2 independent nuclear medicine specialist physicians and were compared with other imaging modalities performed within 15 days of each PET scan.nnnRESULTSnThirty-one patients (10 women and 21 men; median age 59.5 years) underwent a total of 65 PET scans. Twenty-three patients (74%) were untreated at the time of the initial PET scan, whereas 30 of the 34 followup PET scans (88%) were performed in patients who were undergoing immunomodulatory therapy. Comparison of the initial and followup PET scans with other imaging modalities revealed that the sensitivity of PET scanning varied greatly among the different organs studied (range 4.3-100%), while the specificity remained high (range 69.2-100%). Followup PET scans were particularly helpful in assessing central nervous system (CNS) involvement, since the PET scan was able to detect an early therapeutic response of CNS lesions, even before magnetic resonance imaging showed a decrease in their size. PET scanning was also very helpful in evaluating the cardiovascular system, which is a major prognostic factor in ECD, by assessing the heart and the entire vascular tree during a single session.nnnCONCLUSIONnThe results of our large, single-center, retrospective study suggest that the findings of a FDG-PET scan may be interesting in the initial assessment of patients with ECD, but its greater contribution is in followup of these patients.

Maladie d’Erdheim-Chester

Erdheim-Chester disease is a rare and orphan disease. Despite having been overlooked previously, numerous new cases have been diagnosed more recently. The number of Erdheim-Chester disease cases reported has increased substantially: more than 300 new cases have been published in the past 10xa0years. This situation is mainly a result of the generally better awareness among pathologists, radiologists, and clinicians of various aspects of this rare disease. The field has been particularly active in the last few years, with evidence of the efficacy of interferon-α, the description of a systemic pro-inflammatory cytokine signature, and most recently, reports of the dramatic efficacy of BRAF inhibition in severe, BRAF(V600E) mutation-associated cases of Erdheim-Chester disease. Also, BRAF mutations have been found in more than half of the patients with Erdheim-Chester disease who were tested. Detailed elucidation of the pathogenesis of the disease is likely to lead to the development of better targeted and more effective therapies.

Effect of intracoronary administration of AAV1/SERCA2a on ventricular remodelling in patients with advanced systolic heart failure: results from the AGENT-HF randomized phase 2 trial

Restoration of sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a) activity through gene transfer improved cardiac function in experimental and pilot studies in humans with heart failure. The AGENT‐HF (NCT01966887) trial investigated the impact of adeno‐associated virus (AAV1)/SERCA2a on ventricular remodelling using multimodality non‐invasive cardiac imaging.

Intra-aortic balloon pump protects against hydrostatic pulmonary oedema during peripheral venoarterial-extracorporeal membrane oxygenation

Background: Increased left ventricular afterload during peripheral venoarterial-extracorporeal membrane oxygenation (VA-ECMO) support frequently causes hydrostatic pulmonary oedema. Because physiological studies demonstrated left ventricular afterload decrease during VA-ECMO assistance combined with the intra-aortic balloon pump (IABP), we progressively changed our standard practice systematically to associate an IABP with VA-ECMO. This study aimed to evaluate IABP efficacy in preventing pulmonary oedema in VA-ECMO-assisted patients. Methods: A retrospective single-centre study. Results: Among 259 VA-ECMO patients included, 104 received IABP. Weinberg radiological score-assessed pulmonary oedema was significantly lower in IABP+ than IABP– patients at all times after ECMO implantation. This protection against pulmonary oedema persisted when death and switching to central ECMO were used as competing risks (subhazard ratio 0.49, 95% confidence interval (CI) 0.33–0.75; P<0.001). Multivariable analysis retained IABP as being independently associated with a lower risk of radiological pulmonary oedema (odds ratio (OR) 0.4, 95% CI 0.2–0.7; P=0.001) and a trend towards lower mortality (OR 0.54, 95% CI 0.29–1.01; P=0.06). Finally, the time on ECMO free from mechanical ventilation increased in IABP+ patients (2.2±4.3 vs. 0.7±2.0 days; P=0.0003). Less frequent pulmonary oedema and more days off mechanical ventilation were also confirmed in 126 highly comparable IABP+ and IABP– patients, propensity score matched for receiving an IABP. Conclusions: Associating an IABP with peripheral VA-ECMO was independently associated with a lower frequency of hydrostatic pulmonary oedema and more days off mechanical ventilation under ECMO.

HbA1c increase is associated with higher coronary and peripheral atherosclerotic burden in non diabetic patients

BACKGROUND AND AIMSnPrediabetes is associated with an increased risk of developing diabetes and cardiovascular disease. Our objective was to examine the cardiovascular (CV) risk profile of non-diabetic patients with and without prediabetes according to HbA1c, using macroangiopathic imaging biomarkers.nnnMETHODSnOur population consisted of 272 non diabetic patients aged between 40 and 70 years, with a normal fasting plasma glucose (FPG <5.6xa0mmol/L) and at least 1 CV risk factor. Exclusion criteria were prior history of CV disease or clinical evidence of advanced renal disease. Prediabetes was defined as an HbA1c value of 5.7-6.4%. Coronary artery calcium (CAC) score as well as mean common carotid intima media thickness (IMT) and plaque presence were assessed using consensus criteria.nnnRESULTSnCAC score was higher in the prediabetes group compared to non-prediabetic subjects (131.7xa0±xa0295.6 vs. 62.4xa0±xa0178.8 AU, pxa0<xa00.001). Prediabetic subjects had higher mean IMT than non-exposed subjects (0.77xa0±xa00.14 vs. 0.61xa0±xa00.15xa0mm, pxa0<xa00.001). The proportion of prediabetic patients with CACxa0=xa00 was significantly lower compared to non-exposed subjects (35% vs. 63%, pxa0<xa00.01). In contrast, the proportion of patients with a CAC >400 was significantly higher in the prediabetes group (10% vs. 3%, pxa0<xa00.05). Moreover, carotid plaques were significantly more present in patients with prediabetes than in the normoglycemic subjects (pxa0<xa00.01). In a multiple linear regression, IMT was associated with HbA1c continuous levels (pxa0<xa00.001). In addition, logistic regression showed that higher HbA1c levels were associated with CAC and carotid plaques presence (p for trend for allxa0<xa00.001).nnnCONCLUSIONSnAmong patients with normal fasting glucose, HbA1c increase is associated with higher coronary and peripheral atherosclerotic burden in non-diabetic patients.

Early coronary calcifications are related to cholesterol burden in heterozygous familial hypercholesterolemia

BACKGROUNDnThe identification of high-risk patients with heterozygous familial hypercholesterolemia (HeFH) that may benefit from early treatment is challenging. Coronary Artery Calcification (CAC) score accounts for coronary atherosclerotic burden. It has proven its accuracy in cardiovascular risk assessment in the general population but data in HeFH are lacking.nnnOBJECTIVEnThe aim of our study was to assess CAC prevalence and its relationship with lifelong cholesterol exposure, calculated by total cholesterol burden (TCB) in patients with HeFH.nnnMETHODSnA total of 112 HeFH patients (50% males, median age 45xa0years) regularly followed-up since diagnosis were prospectively recruited at Pitié-Salpêtrière Hospital, Paris, France. CAC score was assessed using noncontrast multi-detector computed tomography. TCB was calculated as total cholesterol (TC) × age at diagnosis plus annually assessed TC.nnnRESULTSnThe prevalence of CAC was 58%. Patients without CAC showed lower TCB than patients with CAC (298xa0±xa0110 vs 417.9xa0±xa089 mmol-years/L, Pxa0<xa0.001). Among patients aged <45xa0years (nxa0=xa056), 39% exhibited CAC and a higher TCB compared with patients without CAC (352xa0±xa071 vs 255xa0±xa088 mmol-years/L, Pxa0<xa0.001) due to higher TC levels at diagnosis (10.2xa0±xa02 vs 8.7xa0±xa02xa0mmol/L, Pxa0=xa0.01). Multivariate analysis indicated that TCB was independently associated to CAC.nnnCONCLUSIONSnAsymptomatic HeFH subjects exhibit early coronary atherosclerosis directly associated with TCB burden. CAC score may be useful to identify higher risk HeFH patients who can benefit from earlier and more aggressive treatment.

Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis

Background/Aims According to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment. Methods The reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results. Results A total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462–0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2–7% risk of 2 grades misclassification. Conclusion These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy.

Non-invasive differentiation of idiopathic inflammatory myopathy with cardiac involvement from acute viral myocarditis using cardiovascular magnetic resonance imaging T1 and T2 mapping.

BackgroundIdiopathic inflammatory myopathy (IIM) is a group of autoimmune diseases with systemic myositis which may involve the myocardium. Cardiac involvement in IIM, although often subclinical, may mimic clinical manifestations of acute viral myocarditis (AVM). Our aim was to investigate the usefulness of the combined analysis of cardiovascular magnetic resonance (CMR) T1 and T2 mapping parameters measured both in the myocardium and in the thoracic skeletal muscles to differentiate AVM from IIM cardiac involvement.MethodsSixty subjects were included in this retrospective study (36 male, age 45u2009±u200916xa0years): twenty patients with AVM, twenty patients with IIM and cardiac involvement and twenty healthy controls. Study participants underwent CMR imaging with modified Look-Locker inversion-recovery (MOLLI) T1 mapping and 3-point balanced steady-state-free precession T2 mapping. Relaxation times were quantified after endocardial and epicardial delineation on basal and medial short-axis slices, as well as in different thoracic skeletal muscle groups present in the CMR field-of-view. ROC-Analysis was performed to assess the ability of mapping indices to discriminate the study groups.ResultsMapping parameters in the thoracic skeletal muscles were able to discriminate between AVM and IIM patients. Best skeletal muscle parameters to identify IIM from AVM patients were reduced post-contrast T1 and increased extracellular volume (ECV), resulting in an area under the ROC curve (AUC) of 0.95 for post-contrast T1 and 0.96 for ECV. Conversely, myocardial mapping parameters did not discriminate IIM from AVM patients but increased native T1 (AUC 0.89 for AVM; 0.84 for IIM) and increased T2 (AUC 0.82 for AVM; 0.88 for IIM) could differentiate both patient groups from healthy controls.ConclusionCMR myocardial mapping detects cardiac inflammation in AVM and IIM compared to normal myocardium in healthy controls but does not differentiate IIM from AVM. However, thoracic skeletal muscle mapping was able to accurately discern IIM from AVM.

Phenotypes and survival in Erdheim-Chester disease: Results from a 165-patient cohort

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