Prevalence, patterns and outcomes of cardiac involvement in Erdheim-Chester disease.

AIMS: Cardiac involvement of Erdheim-Chester disease (ECD), a rare L group histiocytosis, has been reported to be associated with poor outcomes, but systematic studies are lacking. The present study aimed to investigate the prevalence, clinical features, imaging features, and prognosis of cardiac involvement in ECD in a large series. METHODS AND RESULTS: All patients with ECD who underwent cardiac magnetic resonance (CMR) imaging between 2003 and 2019 at a French tertiary center were retrospectively included. Primary outcome was all-cause mortality. Secondary outcomes were pericarditis, cardiac tamponade, conduction disorders, device implantation and coronary artery disease (CAD). A total of 200 patients were included [63 (54-71) years, 30% female, 58% BRAFV600E mutated]. Median follow-up was 5.5 years (3.3-9 years). On CMR, right atrioventricular sulcus infiltration was observed in 37% of patients, and pericardial effusion was seen in 24% of patients. In total, 8 patients (4%) had pericarditis (7 acute, 1 constrictive), 10 patients (5%) had cardiac tamponade, 5 patients (2.5%) had ECD-related high-degree conduction disorders, and 45 patients (23%) had CAD. Overall, cardiac involvement was present in 96 patients (48%) and was associated with BRAFV600E mutation [Odds ratio (OR) = 7.4, 95% confidence interval (CI) (3.5-16.8), P < 0.001] and ECD-related clinical events [OR = 5, 95%CI (1.5-21.2), P = 0.004] but not with lower survival in multivariate analysis [adjusted hazard ratio (HR) = 1.4, 95% CI (0.8-2.5), P = 0.2]. CONCLUSION: Cardiac involvement is present in nearly half of ECD patients and is associated with BRAFV600E mutation and complications (pericarditis, cardiac tamponade, and conduction disorders) but not with lower survival.

Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare histiocytosis, considered to be an inflammatory myeloid neoplasm. Tropism for specific involvements of the disease remains unexplained. Vascular endothelial growth factor-A (VEGF) is implicated in cancer pathophysiology and mutations of the RAS oncogene have been shown to induce upregulation of VEGF gene expression. We therefore hypothesized that VEGF might play a particular role in ECD pathophysiology. We conducted a retrospective, single-center study to assess serum VEGF (sVEGF) concentrations and determine whether they were associated with the characteristics of ECD patients, and to determine whether VEGF was expressed by histiocytes. We evaluated 247 ECD patients, 53.4% of whom had sVEGF levels above the normal range (>500 pg/mL). Patients with high sVEGF levels more frequently had cardiac and vascular involvement (58.3% vs. 41.4%, P=0.008 and 70.5% vs. 48.3%, P=0.0004, respectively). In treatment-naïve patients (n=135), the association of C-reactive protein >5 mg/L and sVEGF >500 pg/mL was strongly associated with vascular involvement (odds ratio=5.54 [95% confidence interval: 2.39-13.62], P<0.001), and independently associated with cardiac involvement (odds ratio=3.18 [95% confidence interval: 1.34-7.83], P=0.010) after adjustment for the presence of the BRAF V600E mutation. Changes in sVEGF concentration on treatment were associated with a response of cardiac involvement on consecutive cardiac magnetic resonance images. All histological samples analyzed (n=24) displayed histiocytes with intracytoplasmic expression of VEGF, which was moderate to high in more than 90% of cases. Our study suggests a role for VEGF in cardiac and vascular involvement in ECD.

Comparison of MR T1 and T2 mapping parameters to characterize myocardial and skeletal muscle involvement in systemic idiopathic inflammatory myopathy (IIM).

OBJECTIVES: To compare the performance of magnetic resonance (MR) relaxometry parameters to discriminate myocardial and skeletal muscle inflammation in idiopathic inflammatory myopathy (IIM) patients from healthy controls. MATERIALS AND METHODS: For this retrospective case-control study, 20 consecutive IIM patients (54 ± 18 years, 11 females) with cardiac involvement (troponin level > 50 ng/l) and 20 healthy controls (47 ± 12 years, 9 females) were included. All patients without cardiac MR imaging < 2 weeks prior to the laboratory testings were excluded. T1/T2 relaxation times, as well as T1-derived extracellular volume (ECV), relative tissue T1 shortening ΔT1 = (native T1tissue-post contrast T1tissue)/native T1tissue), and enhancement fraction EHF = (native T1tissue-post contrast T1tissue)/(native T1blood-post contrast T1blood), were compared using Mann-Whitney U test and ROC analysis. RESULTS: All measured MR relaxometry parameters significantly discriminated IIM patients and healthy controls, except T2 in skeletal muscles and ECV in the myocardium. In skeletal muscles, post contrast T1 and T1-derived parameters showed the best performance to discriminate IIM patients from healthy controls (AUC = 0.98 for post contrast T1 and AUC 0.94-0.97 for T1-derived parameters). Inversely, in the myocardium, native T1 and T2 showed better diagnostic performance (AUC = 0.89) than post contrast T1 (AUC = 0.76), ECV (AUC = 0.58), ΔT1 (AUC = 0.80) and EHF (0.82). CONCLUSIONS: MR relaxometry parameters applied to the myocardium and skeletal muscles might be useful to separate IIM patients from healthy controls. However, different tissue composition and vascularization should be taken into account for their interpretation. ΔT1 and EHF may be simple alternatives to ECV in highly vascularized tissues such as the myocardium. KEY POINTS: • MR relaxometry parameters applied to the myocardium and skeletal muscles are highly useful to separate IIM patients from healthy controls. • Different tissue composition and vascularization should be taken into account for T1 and T2 mapping parameter interpretation. • ΔT1 and EHF may be simple alternatives to ECV in highly vascularized tissues such as the myocardium.

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

BACKGROUND: Idiopathic 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. METHODS: Sixty subjects were included in this retrospective study (36 male, age 45 ± 16 years): 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. RESULTS: Mapping 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. CONCLUSION: CMR 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.

Endovascular Treatment of Pelvic Congestion Syndrome: Visual Analog Scale Follow-Up.

Purpose: To evaluate medium-term clinical outcomes of transcatheter embolization and stenting in women with several pelvic venous disorders responsible for chronic pelvic pain and varicose veins of the lower limbs. Materials and Methods: The study population included 327 consecutively recruited patients referred to the interventional radiology unit from January 2014 to December 2019 due to chronic pelvic congestion (91; 27.83%), lower limb varices (15; 4.59%), or a combination of both the symptoms (221; 67.58%). Preprocedural pelvic, transvaginal Doppler ultrasound (US), and MRI were conducted in all the patients and revealed anatomical varicosities and incompetent pelvic veins in 312 patients. In all the patients, selective catheterization demonstrated uterine venous engorgement, ovarian plexus congestion, or pelvic vein filling. Retrograde flow was detected on catheter venography in the left ovarian vein (250; 78%), the right ovarian vein (85; 26%), the left internal iliac vein (222; 68%), and the right internal iliac vein (185; 57%). Patients were followed-up at 1, 6, and 12 months, and years thereafter systematically by the referring angiologist and the interventional radiologist of center. They were contacted by telephone in November and December 2020 to assess pain perception and quality of life by using the visual analog scales from 0 to 10 with assessments made at the baseline and last follow-up. Of the 327 patients (mean age, 42 ± 12 years), 312 patients were suffering from pelvic congestion syndrome and 236 patients was suffering from lower limb varices. All underwent embolization by using ethylene vinyl alcohol copolymer (Onyx®). Eighty-five right ovarian veins, 249 left ovarian veins, 510 tributaries of the right internal iliac vein, and 624 tributaries of the left internal iliac vein were embolized. A cohort of patients also underwent nutcracker syndrome angioplasty (6.7%) and May-Thurner syndrome angioplasty (14%) with a stent placement. Results: The initial technical success rate was 80.9% for embolization of pathological veins and 100% for stenting of stenoses. Overall, 307 patients attended 12-month follow-up visits and 288 (82%) patients completed the telephone survey at mean 39 (±18)-month postintervention. Main pelvic pain significantly improved from 6.9 (±2.4) pre- to 2.0 (±2.4) postembolization (p < 0.001), as did specific symptoms in each category. Improvement or disappearance of pain was achieved in 266/288 (92.36%) patients with improved quality of life in 276/288 (95.8%) patients. There were 16 minor and 4 major adverse events reported on the follow-up. Conclusion: Pelvic vein embolization (Onyx®) is an effective and safe procedure with high clinical success and quality of life improvement rates.