Search

Cardiac amyloidosis is a disease characterised by the accumulation of amyloid protein in the heart tissue. There are several types of amyloidosis, but the most common types affecting the heart are ATTR amyloidosis (caused by transthyretin protein) and AL amyloidosis (caused by abnormal immunoglobulin light chains). Cardiac amyloidosis causes typical signs and symptoms of heart failure. Diagnosis involves a combination of imaging tests such as echocardiography and cardiac magnetic resonance imaging, as well as nuclear imaging scans and tissue biopsies to confirm the presence of amyloid deposits in the heart. Treatment of cardiac amyloidosis depends on the type and severity of the disease and includes medications to manage symptoms as well as treatments targeting the underlying cause of amyloidosis. Importantly, cardiac amyloidosis is a serious condition requiring specialised care from a multidisciplinary team including cardiologists and haematologists as well as other specialists familiar with the management of this rare disease. This is crucial, as early diagnosis and treatment are important for improving outcomes.

AIMS OF THE STUDY: Systemic amyloidoses are rare protein-folding diseases with heterogeneous, often nonspecific clinical presentations. To better understand systemic amyloidoses and to apply state-of-the-art diagnostic pathways and treatment, the interdisciplinary Amyloidosis Network was founded in 2013 at University Hospital Zurich. In this respect, a registry was implemented to study the characteristics and life expectancy of patients with amyloidosis within the area covered by the network. Patient data were collected retrospectively for the period 2005–2014 and prospectively from 2015 onwards. METHODS: Patients aged 18 years or older diagnosed with any subtype of systemic amyloidosis were eligible for inclusion if they were treated in one of the four referring centres (Zurich, Chur, St Gallen, Bellinzona). Baseline data were captured at the time of diagnosis. Follow-up data were assessed half-yearly for the first two years, then annually. RESULTS: Between January 2005 and March 2020, 247 patients were screened, and 155 patients with confirmed systemic amyloidosis were included in the present analysis. The most common amyloidosis type was light-chain (49.7%, n = 77), followed by transthyretin amyloidosis (40%, n = 62) and amyloid A amyloidosis (5.2%, n = 8). Most patients (61.9%, n = 96) presented with multiorgan involvement. Nevertheless, single organ involvement was seen in all types of amyloidosis, most commonly in amyloid A amyloidosis (75%, n = 6). The median observation time of the surviving patients was calculated by the reverse Kaplan-Meier method and was 3.29 years (95% confidence interval [CI] 2.33–4.87); it was 4.87 years (95% CI 3.14–7.22) in light-chain amyloidosis patients and 1.85 years (95% CI 1.48–3.66) in transthyretin amyloidosis patients, respectively. The 1-, 3- and 5-year survival rates were 87.0% (95% CI 79.4–95.3%), 68.5% (95% CI 57.4–81.7%) and 66.0% (95% CI 54.6–79.9%) respectively for light-chain amyloidosis patients and 91.2% (95% CI 83.2–99.8%), 77.0% (95% CI 63.4–93.7%) and 50.6% (95% CI 31.8–80.3%) respectively for transthyretin amyloidosis patients. There was no significant difference between the two groups (p = 0.81). CONCLUSION: During registry set-up, a more comprehensive work-up of our patients suffering mainly from light-chain amyloidosis and transthyretin amyloidosis was implemented. Survival rates were remarkably high and similar between light-chain amyloidosis and transthyretin amyloidosis, a finding which was noted in similar historic registries of international centres. However, further studies are needed to depict morbidity and mortality as the amyloidosis landscape is changing rapidly.

Systemic amyloidoses are chronic diseases with important consequences for patients' quality of life, thus presenting a major medical and socioeconomic burden. This article discusses the current diagnostic challenges and therapy options for systemic amyloidosis and summarizes the activities of the Swiss Amyloidosis Network (SAN) which aims to increase awareness of these rare diseases, include patients in the Swiss Amyloidosis Registry for research purposes and develop interdisciplinary guidelines for diagnosis and therapy of systemic amyloidosis in Switzerland. PEER REVIEWED ARTICLE Peer reviewers: Prof. Dr Ute Hegenbart (University Hospital Heidelberg, Heidelberg, Germany); One anonymous peer reviewer. Submitted: November 30, 2023 CEST; Accepted: December 03, 2023 CEST

AIM: Haemophilic pseudotumours are complications in patients with haemophilia A or B and result from locally repetitive bleeding, mainly in the musculoskeletal system. Abdominal haemophilic pseudotumours are exceptionally rare but may cause severe complications. This systematic review aimed to evaluate therapy strategies for symptomatic abdominal haemophilic pseudotumours. METHODS: We systematically searched three databases (Medline [PubMed], Web of Science and EMBASE) for publications published between 1995 and 2023. Two reviewers independently selected the studies, extracted data and performed a quality assessment using the JBI critical appraisal checklist. RESULTS: From a total of 1199 articles, 39 articles describing 41 cases were included for final analysis. Conservative or interventional treatment was performed in 12 cases. In eight cases, a step-up to surgical therapy after interventional treatment was indicated. Primary surgical therapy was performed in 21 cases. Failure to cure was documented in 50% (n = 6) of patients treated in the first group, with a mortality rate of 16.6% (n = 2). Interventional therapy with a step-up to surgery showed no morbidity or mortality. Primary surgical resection documented favourable results in 66.6% (n = 14), with failure to cure in 9.5% (n = 2) and a mortality rate of 14.3% (n = 3). CONCLUSION: Primary surgical resection can be a first-line therapy for symptomatic, abdominal haemophilic pseudotumours, whereas preoperative embolisation could be used as a bridging therapy before surgery, especially in emergency settings. Diagnostic biopsy and percutaneous drainage should be avoided to prevent complications.

Abstract Aims Cardiac involvement in systemic amyloidosis is a marker of particularly poor prognosis. Cardiac amyloidosis (CA) is characterized by extracellular amyloid deposits inducing heart failure and symptoms of cardiac microvascular disease. While amyloid deposition is most common in the myocardium but also seen in pericardium and endocardium, atria, and vasculature, the role of (micro‐)vascular dysfunction in CA pathophysiology remains still elusive. Because vascular function is associated with cardiovascular risk and severity of heart failure and represents a potential therapeutic target in CA, the present study investigated retinal vascular function, flow‐mediated dilatation (FMD), and pulse‐wave analysis and velocity (PWA/PWV) in patients with CA. Methods and results Flicker‐induced arterial dilatation (FIDa) was measured using dynamic retinal vessel analysis additionally to FMD and PWA/PWV. Thirty‐three patients with CA [age 67 years [interquartile range, IQR, 62, 74], 14 with amyloid light‐chain (AL) and 19 with transthyretin (ATTR) amyloidosis] were prospectively included in this cross‐sectional, observational study and 70 healthy individuals (age 53 years [IQR 39, 67]) served as control. Potential confounders were balanced using entropy balancing propensity score analysis [inverse probability weighting (IPW)]. FIDa was reduced in CA patients (1.52 ± 1.73% vs. 3.09 ± 1.96%, P

In amyloid light-chain (AL) amyloidosis, a small plasma-cell clone, or less frequently a mature B-cell clone, produces toxic monoclonal light chains that can be deposited in the tissues in the form of amyloid fibrils, which can affect the function of potentially multiple organs, including the heart and kidney. The mechanisms behind this organ function impairment are different from plasma-cell myeloma, as are the diagnostic work-up and the treatment strategies. Early pre-symptomatic diagnosis of AL amyloidosis is possible, and it is indeed crucial for effective therapy and the preservation of patients’ quality of life. This is however challenging in the light of a lack of specific clinical symptoms or signs. In the case of suspicious clinical signs, along with the presence of monoclonal gammopathy and elevated validated biomarkers of organ involvement, further diagnostic work-up should be initiated to confirm or exclude AL amyloidosis. Tissue typing of amyloid is also mandatory for the diagnosis of AL amyloidosis. Risk-stratification is essential to guide the therapeutic approach, which has to be individualized and take patient preferences into account. The aim of the therapy is rapid suppression of the production of light chains, to restore organ function, especially cardiac function. The severity of heart involvement and the burden of the pathological light chains are the main prognostic determinants in AL amyloidosis. This review discusses the diagnostic algorithms in suspected amyloidosis, the need for typing of the amyloid for prognostic and therapeutic reasons, and the recent developments in the risk-adapted treatment of AL amyloidosis. We further focus on anti-plasma-cell drugs and autologous stem-cell transplantation, as the tools for hematologic and organ response assessment.

Introduction: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal-dominant disorder, where a TTR mutations lead to amyloid fibril deposits in tissues and consecutively alter organ function. ATTRv is a multisystemic disorder with a heterogeneous clinical presentation. Spinal leptomeningeal depositions are described only scarcely in the literature. Research question: We present a rare case of surgically treated intradural, extra-medullary amyloidosis with respective clinical, diagnostic and surgical features to raise awareness of this rare entity. Material and methods: Clinical, radiological and operative characteristics were retrieved from the electronical patient management system. Additionally, a scoping literature review on leptomeningeal spinal manifestations of ATTRv was performed. Results: A 45-year-old man with a known ATTRv presented with gait disturbance and paresis of the lower extremities. He had been treated with the siRNA therapeutical Patisiran for 13 months under which his symptoms worsened. An MRI of the spine revealed spinal cord compression with myelopathy at the level of T2 with anterior dislocation of the spinal cord due to an intradural, extramedullary lesion. A laminectomy and opening of the dura with a complete resection of the lesion was performed. The histological examination of the biopsy showed amyloid deposits. At six-month follow-up the patient showed complete normalization of the paresis, gait, sensory and urinary disturbances and resumed his work. Discussion and conclusion: Spinal leptomeningeal deposition of amyloid is a rare occurrence within the framework of ATTRv. Micro-neurosurgical complete resection of the lesion is feasible in patients with preoperative myelopathic symptoms and resulted in complete symptom relief in this case.

This article was corrected and republished online on November 4, 2021. Please see Erratum (Swiss Med Wkly. 2021;151:w30104)

Abstract Background In-vivo cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) allows imaging of alterations of cardiac fiber architecture in diseased hearts. Cardiac amyloidosis (CA) causes myocardial infiltration of misfolded proteins with unknown consequences for myocardial microstructure. This study applied CMR DTI in CA to assess microstructural alterations and their consequences for myocardial function compared to healthy controls. Methods Ten patients with CA (8 AL, 2 ATTR) and ten healthy controls were studied using a diffusion-weighed second-order motion-compensated spin-echo sequence at 1.5 T. Additionally, left ventricular morphology, ejection fraction, strain and native T1 values were obtained in all subjects. In CA patients, T1 mapping was repeated after the administration of gadolinium for extracellular volume fraction (ECV) calculation. CMR DTI analysis was performed to yield the scalar diffusion metrics mean diffusivity (MD) and fractional anisotropy (FA) as well as the characteristics of myofiber orientation including helix, transverse and E2A sheet angle (HA, TA, E2A). Results MD and FA were found to be significantly different between CA patients and healthy controls (MD 1.77 ± 0.17 10− 3 vs 1.41 ± 0.07 10− 3 mm2/s, p

Systemic amyloidosis is a heterogeneous group of diseases associated with protein misfolding into insoluble beta-sheet rich structures that deposit extracellularly in different organs, eventually compromising their function. There are more than 30 different proteins, known to be amyloidogenic with “light chain” (AL)-amyloidosis being the most common type, followed by transthyretin (ATTR)-, and amyloid protein A (AA)-amyloidosis. Systemic amyloidosis is a rare disease with an incidence of around 10 patients in 1 million inhabitants. Recently several new therapeutic options have been developed for subgroups of amyloidosis patients, and the introduction of novel therapies for plasma cell myeloma has led to an increase in the therapeutic armamentarium for plasma cell disorders, including AL amyloidosis. Among them, proteasome inhibitors, immunomodulatory agents (-imids), and monoclonal antibodies have been successfully introduced into clinical practice. Still, high-quality data from randomised controlled trials regarding the benefit of these cost-intensive drugs in AL amyloidosis are widely lacking, and due to the rarity of the disease many physicians will not gain routine experience in the management of these frail patients. The diagnosis of AL amyloidosis relies on a close collaboration between clinicians, pathologists, imaging experts, and sometimes geneticists. Diagnosis and treatment options in this complex disorder should be discussed in dedicated multidisciplinary boards. In January 2020, the first meeting of the Swiss Amyloidosis Network took place in Zurich, Switzerland. One aim of this meeting was to establish a consensus guideline regarding the diagnostic work-up and the treatment recommendations for systemic amyloidosis tailored to the Swiss health care system. Forty-five participants from different fields in medicine discussed many aspects of amyloidosis. These are the Swiss Amyloidosis Network recommendations which focus on diagnostic work-up and treatment of AL-amyloidosis.

Abstract Background Cardiac involvement of amyloidosis leads to left-ventricular (LV) wall thickening with progressive heart failure requiring rehospitalization. Cardiovascular magnetic resonance (CMR) is a valuable tool to non-invasively assess myocardial thickening as well as structural changes. Proton CMR spectroscopy (1H-CMRS) additionally allows assessing metabolites including triglycerides (TG) and total creatine (CR). However, opposing results exist regarding utilization of these metabolites in LV hypertrophy or thickening. Therefore, the aim of this study was to measure metabolic alterations using 1H-CMRS in a group of patients with thickened myocardium caused by cardiac amyloidosis. Methods 1H-CMRS was performed on a 1.5 T system (Achieva, Philips Healthcare, Best, The Netherlands) using a 5-channel receive coil in 11 patients with cardiac amyloidosis (60.5 ± 11.4 years, 8 males) and 11 age- and gender-matched controls (63.2 ± 8.9 years, 8 males). After cardiac morphology and function assessment, proton spectra from the interventricular septum (IVS) were acquired using a double-triggered PRESS sequence. Post-processing was performed using a customized reconstruction pipeline based on ReconFrame (GyroTools LLC, Zurich, Switzerland). Spectra were fitted in jMRUI/AMARES and the ratios of triglyceride-to-water (TG/W) and total creatine-to-water (CR/W) were calculated. Results Besides an increased LV mass and a thickened IVS concomitant to the disease characteristics, patients with cardiac amyloidosis presented with decreased global longitudinal (GLS) and circumferential (GCS) strain. LV ejection fraction was preserved relative to controls (60.0 ± 13.2 vs. 66.1 ± 4.3%, p = 0.17). Myocardial TG/W ratios were significantly decreased compared to controls (0.53 ± 0.23 vs. 0.80 ± 0.26%, p = 0.015). CR/W ratios did not show a difference between both groups, but a higher standard deviation in patients with cardiac amyloidosis was observed. Pearson correlation revealed a negative association between elevated LV mass and TG/W (R = − 0.59, p = 0.004) as well as GCS (R = − 0.48, p = 0.025). Conclusions A decrease in myocardial TG/W can be detected in patients with cardiac amyloidosis alongside impaired cardiac function with an association to the degree of myocardial thickening. Accordingly, 1H-CMRS may provide an additional diagnostic tool to gauge progression of cardiac amyloidosis along with standard imaging sequences. Trial registration EK 2013–0132.