Hybrid Magnetic Resonance Positron Emission Tomography Is Associated With Cardiac-Related Outcomes in Cardiac Sarcoidosis.

BACKGROUND: Imaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18F-fluorodeoxyglucose (18F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+). OBJECTIVES: This study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes. METHODS: A total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR-), presence/absence of 18F-FDG (PET+/PET-), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(-), MR(-)PET(+)FOCAL, MR(-)PET(+)DIFFUSE, MR(-)PET(-). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/-)5.7%. Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints. RESULTS: Patients designated MR(+)5.7%PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL, and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint. CONCLUSIONS: Hybrid MR/PET image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image-based classification may have use in prognostication and treatment management in CS.

Sinonasal and ear manifestations of Erdheim-Chester disease.

To calculate the prevalence of sinonasal and ear involvement in an Erdheim-Chester disease (ECD) population, to describe the different ear, nose and throat (ENT) manifestations and to study the association between ENT involvement, other organ involvement, and BRAF mutations. We led a retrospective monocentric study in the national referral center for ECD. One hundred and sixty-two patients with ECD and ENT data were included between January 1, 1980 and December 31, 2020. Ear and nose clinical and radiological findings were noted. We described and studied the prevalence of ENT involvement in ECD population. The association between sinonasal and ear involvement, other organ involvement, and BRAF mutations was calculated. The prevalence of ENT manifestations is around 45%. No clinical rhinologic or otologic signs were specific to ECD. Sinus imaging was abnormal in 70% of cases. A bilateral maxillary sinus frame osteosclerosis was highly specific of ECD. Associations were found between the sinus MRI imaging type and BRAF status, central nervous system involvement, cerebellum involvement and xanthelasma. Sinonasal or ear involvement is frequent in ECD and has specific imaging features for sinuses. Trial registration: #2011-A00447-34.

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.

Prevalence, characteristics and outcome of cardiac manifestations in critically-ill antiphospholipid syndrome patients.

AIMS: Antiphospholipid syndrome (APS) is a rare autoimmune disease defined by thrombotic events occurring in patients with persistent antiphospholipid antibodies. Cardiac manifestations in critically-ill APS patients are poorly investigated. We conducted a study to assess the prevalence, the characteristics and the prognosis of cardiac manifestations in thrombotic APS patients admitted to intensive care unit (ICU). METHODS AND RESULTS: A French, national, multicentre, retrospective study, conducted, from January 2000 to September 2018, including all APS patients admitted to 24 participating centres' ICUs with any new thrombotic (arterial, venous or microvascular) manifestation. Cardiac manifestations were defined as any new cardiac abnormalities relying on clinical examination, cardiac biomarkers, echocardiography, cardiac magnetic resonance (CMR) and coronarography. One hundred and thirty-six patients (female 72%) were included. Mean age at ICU admission was 46 ± 15years. Cardiac manifestations were present in 71 patients (53%). In patients with cardiac involvement, median left ventricular ejection fraction (LVEF) was 40% [28-55], troponin was elevated in 93% patients, coronary angiogram (n = 19, 27%) disclosing a coronary obstruction in 21%. CMR (n = 21) was abnormal in all cases, with late gadolinium enhancement in 62% of cases. Cardiac manifestations were associated with a non-significant increase of mortality (32% vs. 19%, p = 0.08). After 1-year follow-up, median LVEF was 57% [44-60] in patients with cardiac involvement. CONCLUSION: Cardiac involvement is frequent in critically-ill thrombotic APS patients and may be associated to more severe outcome. Increased awareness on this rare cause of myocardial infarction with or without obstructive coronary artery is urgently needed.

Factors associated with implantable cardioverter defibrillators appropriate therapy in cardiac sarcoidosis: a meta-analysis.

BACKGROUND: Patients with cardiac sarcoidosis (CS) are at increased risk of atrioventricular blocks, ventricular arrhythmias, and sudden cardiac death. Objectives We aimed to investigate the characteristics associated with appropriate therapy in implantable cardiac defibrillator (ICD) -implanted CS patients. METHODS: We performed a PubMed and Web of Science search for studies reporting patients with CS who underwent an ICD implantation. The primary criterion was an appropriate therapy. RESULTS: We screened 705 studies, of which 5 were included in the final analysis. We conducted a meta-analysis including 464 patients (mean age 55 years, 282 males (60%)). The mean follow-up was 3.5 years. Among the 464 patients, 180 received an appropriate therapy (39%). Patients who received an appropriate therapy were younger (-3.33, 95% confidence interval (CI) -6.42 to -0.23, p=0.004), were more likely to be male (OR 2.06, 95% CI 1.37-3.09, p=0.0005), had a lower left ventricular ejection fraction (LVEF) (-10.5, 95% CI -18.23 to -2.78, p=0.008), had a higher rate of complete heart block (OR 2.19, 95% CI 1.20 to 3.99, p=0.01), and more frequently had ventricular pacing (OR 6.44 95% CI 2.57 to 16.16, p<0.0001). CONCLUSIONS: Appropriate ICD therapy during CS is associated with young age, male sex, low LVEF, history of complete heart block, and ventricular pacing. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 17-23).