Dan Toledano

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

OBJECTIVE (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. METHODS Twenty-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. RESULTS PET 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). CONCLUSION Our 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.

Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAFV600E-Mutated Erdheim-Chester Disease

PURPOSE Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. PATIENTS AND METHODS Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). RESULTS All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. CONCLUSION Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.

Takayasu Arteritis in France: A Single-Center Retrospective Study of 82 Cases Comparing White, North African, and Black Patients

We conducted a single-center retrospective study to compare the characteristics of Takayasu arteritis (TA) among white, North African, and black patients in a French tertiary care center (Hospital Pitié-Salpêtrière, Paris). Eighty-two patients were studied (82.9% female) during a median follow-up of 5.1 years (range, 1 mo to 30 yr). Among these 82 patients, 39 (47.6%) were white, 20 (24.4%) were North African, and 20 (24.4%) were black patients. Median age at diagnosis was 39.3 years (range, 14-70 yr) in white patients vs. 28.4 years (range, 12-54 yr) in North African (p = 0.02), and 28.0 years (range, 13-60 yr) in black patients (p = 0.08). Patients aged >40 years at TA onset were more frequently white than non-white (40.0% vs. 18.6%, p = 0.03). North African patients had more frequent occurrence of ischemic stroke (p = 0.03) and poorer survival (p = 0.01) than white patients. Type V of the Hata classification was the most frequent type among white (38.5%), North African (65.0%), and black patients (40.0%). Corticosteroids were used in 96.1% of patients. Fifty-three percent of white and North African patients, and 44% of black patients required a second line of immunosuppressive treatment (p = 0.60). Vascular surgical procedures were respectively performed in 46.1%, 50.0%, and 55.0% of white, North African, and black patients, p = 0.81. The 5-year and 10-year survival rates were 100% and 95.0%, respectively, in white patients; 67.4% at both 5 years and 10 years in North African patients; and 100% at both 5 years and 10 years in black patients. This study is one of the first direct comparisons of TA profiles among patients of distinct ethnic backgrounds. Our data support the idea that late-onset TA or an overlap between TA and large-vessel giant cell arteritis may be observed in white patients. North African patients have a higher occurrence of ischemic stroke and poorer survival than white patients. Abbreviations: ACR = American College of Rheumatology, CRP = C-reactive protein, CT = computed tomography, ESR = erythrocyte sedimentation rate, FDG = 18F-fluorodeoxyglucose, HIV = human immunodeficiency virus, MRI = magnetic resonance imaging, PET = positron emission tomography, TA = Takayasu arteritis, TNF = tumor necrosis factor.

Images in cardiovascular medicine. Cardiac involvement in Erdheim-Chester disease: magnetic resonance and computed tomographic scan imaging in a monocentric series of 37 patients.

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis, characterized by the xanthomatous infiltration of tissues with foamy CD68+/CD1a− histiocytes. By January 2009, >320 cases had been published in the medical literature. Bone pain is the most frequent symptom. Approximately half of patients have extraskeletal manifestations including exophthalmos, xanthelasma, interstitial lung disease, retroperitoneal “fibrosis” with perirenal or ureteral obstruction, renal failure, diabetes insipidus, and central nervous system and cardiovascular involvement. Interferon-α is the recommended first-line therapy but is decided after a case-by-case analysis.1 Cardiovascular manifestations of ECD are underdiagnosed, as we have shown in our analysis in 2004 of the 178 cases known at that time.2 Among these, we analyzed 72 patients with cardiovascular involvement and found 54 (75%) with heart involvement: pericardial infiltration in 32 patients (44%) (leading to tamponade in 5 cases), myocardial infiltration in 22 cases (31%), a right atrial tumor in 6 patients, and a symptomatic valvular heart disease in 6 patients (3 aortic and 3 mitral regurgitations); 19 patients (26%) had heart failure, leading to death in 8 cases; myocardial infarction (MI) was reported in 6 cases, leading to death in 2. Forty …Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis, characterized by the xanthomatous infiltration of tissues with foamy CD68+/CD1a− histiocytes. By January 2009, >320 cases had been published in the medical literature. Bone pain is the most frequent symptom. Approximately half of patients have extraskeletal manifestations including exophthalmos, xanthelasma, interstitial lung disease, retroperitoneal “fibrosis” with perirenal or ureteral obstruction, renal failure, diabetes insipidus, and central nervous system and cardiovascular involvement. Interferon-α is the recommended first-line therapy but is decided after a case-by-case analysis.1 Cardiovascular manifestations of ECD are underdiagnosed, as we have shown in our analysis in 2004 of the 178 cases known at that time.2 Among these, we analyzed 72 patients with cardiovascular involvement and found 54 (75%) with heart involvement: pericardial infiltration in 32 patients (44%) (leading to tamponade in 5 cases), myocardial infiltration in 22 cases (31%), a right atrial tumor in 6 patients, and a symptomatic valvular heart disease in 6 patients (3 aortic and 3 mitral regurgitations); 19 patients (26%) had heart failure, leading to death in 8 cases; myocardial infarction (MI) was reported in 6 cases, leading to death in 2. Forty …

Cluster Analysis of Arterial Involvement in Takayasu Arteritis Reveals Symmetric Extension of the Lesions in Paired Arterial Beds

OBJECTIVE The determinants of vessel targeting are largely unknown in vasculitides. This study was undertaken to identify patterns of vascular involvement in Takayasu arteritis (TA), using objective classification of vascular beds. We postulated that cluster analysis could unveil preferential associations between vascular beds commonly affected by TA. METHODS Peripheral vascular Doppler, computed tomography angiography, and angio-magnetic resonance imaging data from 82 patients with TA (according to the American College of Rheumatology criteria) were studied between January 1995 and May 2006. Cross-relationships of involvement between 24 main arteries were assessed using the phi correlation coefficient. Identification of patterns of vascular involvement was performed using agglomerative hierarchical cluster analysis. RESULTS Data were obtained from 82 patients (68 women [82.9%] and 14 men [17.1%]). The median duration of followup was 5.1 years (range 1 month to 30 years). For 16 (80%) of 20 paired arteries, the highest correlation of involvement was observed with the contralateral artery. Conversely, disease extension was contiguous in the aorta. Cluster analysis further confirmed that all paired arterial beds, except for the internal and external carotid arteries, clustered with their contralateral counterpart and that the aortic arch, the descending thoracic aorta, and the abdominal aorta clustered together. CONCLUSION Our findings reveal that TA lesions mostly develop in a symmetric manner in paired vascular territories and that disease extension is contiguous in the aorta. This may prove useful for improving the radiologic followup of patients with TA and for providing a pattern for further investigations focusing on the mechanisms of vessel specificity in vasculitides.

Cardiac Involvement in Erdheim-Chester Disease Magnetic Resonance and Computed Tomographic Scan Imaging in a Monocentric Series of 37 Patients

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis, characterized by the xanthomatous infiltration of tissues with foamy CD68+/CD1a− histiocytes. By January 2009, >320 cases had been published in the medical literature. Bone pain is the most frequent symptom. Approximately half of patients have extraskeletal manifestations including exophthalmos, xanthelasma, interstitial lung disease, retroperitoneal “fibrosis” with perirenal or ureteral obstruction, renal failure, diabetes insipidus, and central nervous system and cardiovascular involvement. Interferon-α is the recommended first-line therapy but is decided after a case-by-case analysis.1 Cardiovascular manifestations of ECD are underdiagnosed, as we have shown in our analysis in 2004 of the 178 cases known at that time.2 Among these, we analyzed 72 patients with cardiovascular involvement and found 54 (75%) with heart involvement: pericardial infiltration in 32 patients (44%) (leading to tamponade in 5 cases), myocardial infiltration in 22 cases (31%), a right atrial tumor in 6 patients, and a symptomatic valvular heart disease in 6 patients (3 aortic and 3 mitral regurgitations); 19 patients (26%) had heart failure, leading to death in 8 cases; myocardial infarction (MI) was reported in 6 cases, leading to death in 2. Forty …Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis, characterized by the xanthomatous infiltration of tissues with foamy CD68+/CD1a− histiocytes. By January 2009, >320 cases had been published in the medical literature. Bone pain is the most frequent symptom. Approximately half of patients have extraskeletal manifestations including exophthalmos, xanthelasma, interstitial lung disease, retroperitoneal “fibrosis” with perirenal or ureteral obstruction, renal failure, diabetes insipidus, and central nervous system and cardiovascular involvement. Interferon-α is the recommended first-line therapy but is decided after a case-by-case analysis.1 Cardiovascular manifestations of ECD are underdiagnosed, as we have shown in our analysis in 2004 of the 178 cases known at that time.2 Among these, we analyzed 72 patients with cardiovascular involvement and found 54 (75%) with heart involvement: pericardial infiltration in 32 patients (44%) (leading to tamponade in 5 cases), myocardial infiltration in 22 cases (31%), a right atrial tumor in 6 patients, and a symptomatic valvular heart disease in 6 patients (3 aortic and 3 mitral regurgitations); 19 patients (26%) had heart failure, leading to death in 8 cases; myocardial infarction (MI) was reported in 6 cases, leading to death in 2. Forty …

Multislice computed tomography to rule out coronary allograft vasculopathy in heart transplant patients

BACKGROUND This study assessed if invasive coronary angiogram (CA) could be replaced by multislice (64- or 256-row) computed tomography (MSCT) to systematically rule out coronary allograft vasculopathy in heart transplant patients. METHODS Electrocardiogram-gated contrast-enhanced MSCT (64-row for the first 25 patients and 256-row for the others) was compared with CA. MSCT parameters, adapted to the patients weight, included 120 kV, 800 mAs, 0.625-mm slice thickness, and 0.42/0.27-second rotation time. The primary end point was the negative predictive value (NPV) of MSCT for the detection of significant (>50%) coronary stenosis. Secondary end points were the comparison of X-ray (mSv) and iodine contrast agent (ml) exposures. RESULTS The study prospectively included 102 patients (mean age, 53±14 years). Transplantation occurred 6±5 years before inclusion. At CA, 41.8% had stenosis ≤50% and 8% had stenosis>50%. Among the 1,308 angiographic coronary segments ≥1.5 mm, 1,250 (95.6%) were evaluable by MSCT. The NPV of MSCT was 96.6% by patient analysis and 99.7% by segment analysis. The positive predictive value (PPV) was 45.5%. The total volume of contrast agent was 139±43 vs 91±12 vs 56±19 ml (p<0.05) with 64-row MSCT, 256-row MSCT, and CA, respectively. The effective radiation dose was higher using retrospective gating (17.8±5.5 mSv, p<0.05), but similar with prospective gating (6.2±1.9 mSv, p = 0.571) compared with CA (6.0±3.5 mSv). CONCLUSION Newer generations of MSCT (64- or 256-row) have a good NPV and may represent an alternative to invasive CA to rule out significant (>50%) coronary vasculopathy in heart transplant patients, despite a low PPV.

Evaluation of an edge-based registration method: application to magnetic resonance first-pass myocardial perfusion data

PURPOSE Quantification of cardiac magnetic resonance (CMR) myocardial perfusion remains time consuming since it requires manual interventions to compensate for motion. Thus, the aim of this study was to evaluate a semiautomated registration method. MATERIALS AND METHODS A rigid edge-based registration algorithm was applied on 10 patients who had rest and stress CMR acquisitions on three slice levels (apical, midventricular and basal slices). Registration efficiency was assessed qualitatively by evaluating the quality of k-means maps in terms of symmetry and heart structures identification before and after registration and quantitatively by estimating noise amplitude within the myocardium. Finally, residual registration errors were manually estimated. RESULTS Before registration, k-means maps were satisfactory for 15 of 30 slices at rest and for only 5 of 30 slices during stress. After registration, the k-means maps quality was satisfactory for 29 of 30 slices at rest and for 30 of 30 slices during stress. Moreover, registration reduced noise amplitude from 49±26 to 29±11 at rest (P<.01) and from 52±14 to 30±10 during stress (P<.01). The residual horizontal and vertical shifts were 0.06±0.12 and 0.04±0.08 mm at rest and 0.32±0.69 and 0.28±0.53 mm at stress. CONCLUSION The registration was successfully tested on rest and stress CMR perfusion data. It provides a valuable basis for quantitative evaluation of myocardial perfusion.

Cardiac Involvement in Erdheim-Chester Disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis, characterized by the xanthomatous infiltration of tissues with foamy CD68+/CD1a− histiocytes. By January 2009, >320 cases had been published in the medical literature. Bone pain is the most frequent symptom. Approximately half of patients have extraskeletal manifestations including exophthalmos, xanthelasma, interstitial lung disease, retroperitoneal “fibrosis” with perirenal or ureteral obstruction, renal failure, diabetes insipidus, and central nervous system and cardiovascular involvement. Interferon-α is the recommended first-line therapy but is decided after a case-by-case analysis.1 Cardiovascular manifestations of ECD are underdiagnosed, as we have shown in our analysis in 2004 of the 178 cases known at that time.2 Among these, we analyzed 72 patients with cardiovascular involvement and found 54 (75%) with heart involvement: pericardial infiltration in 32 patients (44%) (leading to tamponade in 5 cases), myocardial infiltration in 22 cases (31%), a right atrial tumor in 6 patients, and a symptomatic valvular heart disease in 6 patients (3 aortic and 3 mitral regurgitations); 19 patients (26%) had heart failure, leading to death in 8 cases; myocardial infarction (MI) was reported in 6 cases, leading to death in 2. Forty …Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis, characterized by the xanthomatous infiltration of tissues with foamy CD68+/CD1a− histiocytes. By January 2009, >320 cases had been published in the medical literature. Bone pain is the most frequent symptom. Approximately half of patients have extraskeletal manifestations including exophthalmos, xanthelasma, interstitial lung disease, retroperitoneal “fibrosis” with perirenal or ureteral obstruction, renal failure, diabetes insipidus, and central nervous system and cardiovascular involvement. Interferon-α is the recommended first-line therapy but is decided after a case-by-case analysis.1 Cardiovascular manifestations of ECD are underdiagnosed, as we have shown in our analysis in 2004 of the 178 cases known at that time.2 Among these, we analyzed 72 patients with cardiovascular involvement and found 54 (75%) with heart involvement: pericardial infiltration in 32 patients (44%) (leading to tamponade in 5 cases), myocardial infiltration in 22 cases (31%), a right atrial tumor in 6 patients, and a symptomatic valvular heart disease in 6 patients (3 aortic and 3 mitral regurgitations); 19 patients (26%) had heart failure, leading to death in 8 cases; myocardial infarction (MI) was reported in 6 cases, leading to death in 2. Forty …

Left atrial high-grade undifferentiated pleomorphic sarcoma protruding through the mitral valve.

Primary cardiac tumors are uncommon. Malignant neoplasms account for 25%, including 75% of cardiac sarcomas. A 53-year-old female complained of exertional dyspnea and orthopnea. Chest computed tomography revealed a mass within the left atrium. Echocardiography confirmed a bilobed left atrial mass protruding through the mitral valve orifice. The tumor was completely resected and was histologically diagnosed as a high-grade pleomorphic sarcoma. A 13-month follow-up was achieved without any recurrence on magnetic resonance imaging.