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 mm 2 /s, p < 0.001; FA 0.25 ± 0.04 vs 0.35 ± 0.03, p < 0.001). MD demonstrated an excellent correlation with native T1 ( r = 0.908, p < 0.001) while FA showed a significant correlation with ECV in the CA population ( r = − 0.851, p < 0.002). HA exhibited a more circumferential orientation of myofibers in CA patients, in conjunction with a higher TA standard deviation and a higher absolute E2A sheet angle. The transmural HA slope was found to be strongly correlated with the global longitudinal strain ( r = 0.921, p < 0.001). Conclusion CMR DTI reveals significant alterations of scalar diffusion metrics in CA patients versus healthy controls. Elevated MD and lower FA values indicate myocardial disarray with higher diffusion in CA that correlates well with native T1 and ECV measures. In CA patients, CMR DTI showed pronounced circumferential orientation of the myofibers, which may provide the rationale for the reduction of global longitudinal strain that occurs in amyloidosis patients. Accordingly, CMR DTI captures specific features of amyloid infiltration, which provides a deeper understanding of the microstructural consequences of CA. Electronic supplementary material The online version of this article (10.1186/s12968-019-0563-2) contains supplementary material, which is available to authorized users.
Daratumumab, an anti‐CD38 antibody, is effective in AL amyloidosis with low tumor burden. Data of daratumumab treatment in patients with AL amyloidosis but high tumor burden (≥10% bone marrow plasma cells) are limited. We report retrospective data of 10 consecutive patients with high tumor burden treated with daratumumab for relapsed/refractory AL amyloidosis. The median age at diagnosis was 62.3 years; all patients had cardiac involvement, and six (60%) patients had renal involvement. Median bone marrow plasma cell infiltration was 15% (range 10%‐40%), and the median difference between involved and noninvolved free light‐chains (dFLC) was 446 mg/L (range 102‐1392 mg/L). Patients had a median of three prior lines of therapy, including bortezomib in all patients and lenalidomide in seven (70%) patients. The median time to first hematological response was 14 days (range 7‐28 days), and the median time to best hematological response was 64 days (range 7‐301 days). The hematological overall response was 90%, with high‐quality response (≥ very good partial remission [VGPR]) in 70% of the patients. Fifty percent of the patients had a cardiac response after a median of 3.8 months (range 0.7‐9.1). Infusion‐related adverse events ≤ grade 2 occurred in seven (70%) patients and grade 3 adverse events in one patient. After a median follow‐up time of 10 months, eight (80%) patients continued to receive daratumumab. We conclude that daratumumab is a very effective and safe treatment option in AL patients with relapsed/refractory disease and high disease burden at diagnosis. Daratumumab leads to rapid disease control and improvement of organ function.
Amylodiosis is a systemic disease characterized by extracellular deposits of insoluble amyloid in various tissues and organs. Cardiac amyloidosis is a frequent feature of the disease, causing a progressive, restrictive type of cardiomyopathy, and is associated with adverse clinical outcomes and increased mortality. The typical clinical presentation in patients with cardiac amyloidosis is heart failure (HF) with preserved ejection fraction. Most patients present with typical symptoms and signs of HF, such as exertional dyspnea, pretibial edema, pleural effusions and angina pectoris due to microcirculatory dysfunction. However, patients may also frequently encounter various arrhythmias, such as atrioventricular nodal block, atrial fibrillation and ventricular tachyarrhythmias. The management of arrhythmias in cardiac amyloidosis patients with drugs and devices is often a clinical challenge. Moreover, predictors of life-threatening arrhythmic events are not well defined. This review intends to give a deepened insight into the arrhythmic features of cardiac amyloidosis by discussing the pathogenesis of these arrhythmias, addressing the challenges in risk stratification and strategies for management in these patients.
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.
BackgroundCardiac 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.Methods1H-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.ResultsBesides 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).ConclusionsA 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 registrationEK 2013–0132.
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