Luspatercept, a two-edged sword in beta-thalassemia-associated paravertebral extramedullary hematopoietic masses (EHMs).

Paravertebral extramedullary hematopoietic masses (EHMs) account for up to 15% of extramedullary pseudotumors in beta-thalassemia (BT) and are most likely related to compensatory hematopoiesis. In most cases, pseudotumors are incidentally detected, as the majority of patients are asymptomatic. Since June 2020, luspatercept is approved for the treatment of patients with BT who require regular red blood cell transfusions. Data addressing the safety and efficacy of luspatercept in patients with BT-associated EHMs are pending. To date (May 2022), paravertebral EHMs were observed in two asymptomatic patients out of currently 43 adult patients with BT registered at the Adult Hemoglobinopathy Outpatient Unit of the University Hospital Essen, Germany. In one of them, a paravertebral EHM was diagnosed more than 10 years prior to referral. Throughout observation time, treatment with luspatercept was associated with a clinically significant reduction in transfusion burden while allowing to maintain a baseline hemoglobin concentration of ≥10 g/dL aiming to suppress endogenous (ineffective) erythropoiesis associated with BT. Considering the rarity of paravertebral EHMs in BT, luspatercept might potentially represent a novel therapeutic option for these often-serious disease-associated complications. However, appropriate follow-up investigations are recommended to detect (early) treatment failures secondary to an undesired luspatercept-associated erythroid expansion.

18F-flutemetamol positron emission tomography in cardiac amyloidosis.

PURPOSE: Bone-tracer scintigraphy has an established role in diagnosis of cardiac amyloidosis (CA) as it detects transthyretin amyloidosis (ATTR). Positron emission tomography (PET) with amyloid tracers has shown high sensitivity for detection of both ATTR and light-chain (AL) CA. We aimed to investigate the accuracy of 18F-flutemetamol in CA. METHODS: We enrolled patients with CA or non-amyloid heart failure (NA-HF), who underwent cardiac 18F-flutemetamol PET/MRI or PET/CT. Myocardial and blood pool standardized tracer uptake values (SUV) were estimated. Late gadolinium enhancement (LGE) and T1 mapping/ extracellular volume (ECV) estimation were performed. RESULTS: We included 17 patients (12 with CA, 5 with NA-HF). PET/MRI was conducted in 13 patients, while PET/CT was conducted in 4. LGE was detected in 8 of 9 CA patients. Global relaxation time and ECV were higher in CA (1448 vs. 1326, P = 0.02 and 58.9 vs. 33.7%, P = 0.006, respectively). Positive PET studies were demonstrated in 2 of 12 patients with CA (AL and ATTR). Maximal and mean SUV did not differ between groups (2.21 vs. 1.69, P = 0.18 and 1.73 vs. 1.30, P = 0.13). CONCLUSION: Although protein-independent binding is supported by our results, the diagnostic yield of PET was low. We demonstrate here for the first time the low sensitivity of PET for CA.

Rare variant (p.Ser43Asn) of familial transthyretin amyloidosis associated with isolated cardiac phenotype: A case series with literature review.

BACKGROUND: p.Ser43Asn is a very rare transthyretin (TTR) mutation leading to familial amyloidosis of transthyretin type, ATTR amyloidosis. It was previously observed in four patients worldwide and is associated almost invariably with an isolated cardiac phenotype. METHODS AND RESULTS: We report here on an Italian family with early-onset cardiomyopathy and aggressive disease course in the affected individuals leading untreated to cardiac death before 55 years of age. We describe the clinical phenotype and imaging findings of two affected siblings, who were treated with tafamidis at an early disease stage, and their affected mother, who died 9 years ago due to refractory heart failure. The review of the available literature highlights the fact that until recently ATTR amyloidosis may have been misdiagnosed as other types of hypertrophic cardiomyopathy. CONCLUSION: A better characterization of the genotype-phenotype associations is crucial to achieve optimal outcomes and facilitate informed decisions when treating individuals with rare mutations.

Generating Virtual Short Tau Inversion Recovery (STIR) Images from T1- and T2-Weighted Images Using a Conditional Generative Adversarial Network in Spine Imaging.

Short tau inversion recovery (STIR) sequences are frequently used in magnetic resonance imaging (MRI) of the spine. However, STIR sequences require a significant amount of scanning time. The purpose of the present study was to generate virtual STIR (vSTIR) images from non-contrast, non-fat-suppressed T1- and T2-weighted images using a conditional generative adversarial network (cGAN). The training dataset comprised 612 studies from 514 patients, and the validation dataset comprised 141 studies from 133 patients. For validation, 100 original STIR and respective vSTIR series were presented to six senior radiologists (blinded for the STIR type) in independent A/B-testing sessions. Additionally, for 141 real or vSTIR sequences, the testers were required to produce a structured report of 15 different findings. In the A/B-test, most testers could not reliably identify the real STIR (mean error of tester 1-6: 41%; 44%; 58%; 48%; 39%; 45%). In the evaluation of the structured reports, vSTIR was equivalent to real STIR in 13 of 15 categories. In the category of the number of STIR hyperintense vertebral bodies (p = 0.08) and in the diagnosis of bone metastases (p = 0.055), the vSTIR was only slightly insignificantly equivalent. By virtually generating STIR images of diagnostic quality from T1- and T2-weighted images using a cGAN, one can shorten examination times and increase throughput.

The Role of Whole-Body Magnetic Resonance Imaging (WB-MRI) in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).

In PNH thromboembolic events (TEs) represent the leading cause of morbidity and mortality. Between Dec 2013 and Jan 2016 37 PNH patients (pts) (23 PNH, 14 AA/PNH; 51% (19/37) females; median age 44 years, median D-dimer levels 0.22 mg/l) were examined with a whole-body magnetic resonance imaging (WB-MRI) scan at 1.5 T to detect TEs. Pts were treated according to German PNH guidelines, including eculizumab therapy. 64% (24/37) of the pts had no documented TEs prior to observation. Two pts had suspected TEs in their clinical history. 29% of the pts (11/37) had a known history of venous thromboses (deep venous thrombosis (DVT) (5/11), portal venous thrombosis (PVT) (4/11), vena caval thrombosis (VCT) (2/11). A myocardial infarction was reported in one pt, and two had a cerebral venous sinus thrombosis (CVST) or a thalamic infarction. Six pts (16%) had at least two prior TEs. In pts with prior TEs no progression of the existing TEs was observed. In pts on eculizumab and prior TEs as well as treatment-naïve pts silent bone and renal infarctions were detected. Furthermore, a clinically non-critical arterial occlusion was identified. WB-MRI scans present a novel, non-invasive method to assess the complete vascular status of PNH pts and allow the detection of previously undiagnosed vascular complications, affecting treatment indications and regimens.

No protection of heart, kidneys and brain by remote ischemic preconditioning before transfemoral transcatheter aortic valve implantation: Interim-analysis of a randomized single-blinded, placebo-controlled, single-center trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) reduces myocardial injury and improves clinical outcome in patients undergoing coronary revascularization, but only in the absence of propofol-anesthesia. We investigated whether RIPC provides protection of heart, kidneys and brain and improves outcome in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI). METHODS: Patients undergoing TF-TAVI were randomized to receive RIPC (3cycles of 5min left upper arm ischemia and 5min reperfusion) or placebo. The primary endpoint was myocardial injury, reflected by the area under the curve for serum troponin I concentrations (AUC-TnI) over the first 72h. Secondary endpoints included the incidences of periprocedural myocardial infarction, delayed gadolinium enhancement on postprocedural cardiac MRI, acute kidney injury, periprocedural stroke, and the incidence and volume of new lesions on postprocedural cerebral MRI. All-cause and cardiovascular mortality and major adverse cardiac and cerebrovascular events (MACCE) were assessed over 1-year follow-up. A prespecified interim-analysis was performed after the last patient had completed 1-year follow-up (NCT02080299). RESULTS: 100 consecutive patients were enrolled between September 2013 and June 2015. There were no significant between-group differences in the primary endpoint of peri-interventional myocardial injury (ratio RIPC/placebo AUC-TnI: 0.87, 95% CI: 0.57-1.34, p=0.53) or the secondary endpoints of cardiac, renal and cerebral impairment. There was no significant treatment effect in subgroup-analyses of patients undergoing cardiac or cerebral MRI. Mortality and MACCE did not differ. No RIPC-related adverse events were observed. CONCLUSIONS: RIPC did neither protect heart, kidneys and brain nor improve clinical outcome in patients undergoing TF-TAVI.