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Amyloidosis is characterized by a disorder of protein conformation and metabolism, resulting in deposits of insoluble fibrils in various organs causing functional disturbances. Amyloidosis can also affect the heart. Cardiac amyloidosis tends to have a poor prognostic outcome if diagnosed at a late stage. Therefore, early diagnosis and initiation of therapy as well as monitoring of treatment response are crucial to improve outcomes and to learn more about its pathophysiology and clinical course. We present an 83-year-old woman with cardiac transthyretin amyloidosis (ATTR) who was treated with tafamidis. The patient significantly improved 18 months after initiation of therapy with regards to exercise capacity and quality of life. In addition to standard diagnostic methods, we used magnetocardiography (MCG) to monitor potential treatment response by detecting changes in the magnetic field of the heart. MCG is a non-invasive method that detects the cardiac magnetic field generated by electrical currents in the heart with high sensitivity. We have recently shown that this magnetic field changes in various types of cardiomyopathies may be used as a non-invasive screening tool. We determined previously that an MCG vector ≥0.052 was the optimal threshold to detect cardiac amyloidosis. The patient's MCG was measured at various time points during therapy. At the time of diagnosis, the patient's MCG vector was 0.052. After starting therapy, the MCG vector increased to 0.090, but improved to 0.037 after 4 months of therapy. The MCG vector reached a value of 0.017 after 5 months of therapy with tafamidis, and then increased slightly after 27 months to a value of 0.027 (<0.052). Data from this case support our previous findings that MCG may be used to monitor treatment response non-invasively. Further research is needed to understand the unexpected changes in the MCG vector that were observed at the beginning of therapy and later in the course. Larger studies will be necessary to determine how these changes in the electromagnetic field of the heart are related to structural changes and how they affect clinical outcomes.

Recent evidence highlights the efficacy of mavacamten in reducing left ventricular outflow tract (LVOT) gradients in patients with hypertrophic cardiomyopathy (HCM), which is illustrated in this case. Additionally, the potential of magnetocardiography (MCG) as a novel, objective diagnostic and monitoring tool for nonischemic cardiomyopathies is demonstrated.

Aims: Myocardial inflammation in cardiac amyloidosis is associated with poor clinical outcomes. This study aimed to (a) investigate the relationship between peripheral blood cytokine levels and the presence of inflammatory cells within the myocardium, and to (b) evaluate the potential of cytokines as predictors of major adverse cardiovascular events (MACE) in transthyretin (ATTR) and immunoglobulin light chain (AL) cardiac amyloidosis. Methods: Peripheral blood samples were collected from 50 patients with cardiac ATTR or AL amyloidosis between 2018 and 2023 at baseline and every three months during follow-up visits. Cytokine analysis was performed using Olink’s Proximity Extension Assay. For MACE prediction analysis, only patients with MACE occurring within ±14 days of a study visit were included (n = 16). Associations were evaluated using linear models. Results: No significant associations were identified between the EMB-confirmed myocardial presence of inflammatory cells and cytokine levels. There was a trend of weak-to-moderate associations between serial blood cytokine levels and MACE, albeit this was non-significant after adjustment for multiple testing (FDR): r2 = 0.28 for PON3 (p = 0.00075, FDR = 0.28), SIGLEC1 (p = 0.00077, FDR = 0.28), and IL-6 (p = 0.00086, FDR = 0.31). Conclusions: Peripheral blood cytokine levels were not reliable biomarkers for the myocardial presence of inflammatory cells. PON3, SIGLEC1, and IL-6 demonstrated a statistically non-significant trend of a weak-to-moderate association with MACE in cardiac amyloidosis. Since we recently demonstrated that amyloidosis with an inflammatory component is associated with poor outcomes, these additional findings underscore the need for alternative approaches to identify and manage inflammation in this patient population.

BackgroundThe diagnosis of inflammatory cardiomyopathies remains challenging. Life-threatening conditions such as acute coronary syndrome (ACS) always have to be considered as differential diagnoses due to similarities in presentation. Diagnostic methods for inflammatory cardiomyopathy include endomyocardial biopsy (EMB), cardiac magnetic resonance imaging (CMR), and positron emission tomography-computed tomography (PET-CT). We report a case in whom magnetocardiography (MCG) led to an initial diagnosis of inflammatory cardiomyopathy and in whom MCG was used for subsequent monitoring of treatment response under immunosuppression.Case presentationA 53-year-old man presented with two recurrent episodes of inflammatory cardiomyopathy within a 2-year period. The patient initially presented with reduced exercise capacity. Echocardiography revealed a moderately reduced left ventricular ejection fraction (LVEF 40%). Coronary angiography ruled out obstructive coronary artery disease (CAD) and an EMB was performed. The EMB revealed inflammatory cardiomyopathy without viral pathogens or replication. Moreover, we performed MCG, which confirmed a pathological Tbeg-Tmax vector of 0.108. We recently established a cutoff value of Tbeg-Tmax of 0.051 or greater for the diagnosis of inflammatory cardiomyopathy. Immunosuppressive therapy with prednisolone was initiated, resulting in clinical improvement and an LVEF increase from 40% to 45% within 1 month. Furthermore, the MCG vector improved to 0.036, which is considered normal based on our previous findings. The patient remained clinically stable for 23 months. During a routine follow-up, MCG revealed an abnormal Tbeg-Tmax vector of 0.069. The patient underwent additional testing including routine laboratory values, echocardiography (LVEF 35%), and PET-CT. PET-CT revealed increased metabolism in the myocardium—primarily in the lateral wall. Therapy with prednisolone and azathioprine was initiated and MCG was used to monitor the effect of immunosuppressive therapy.ConclusionIn addition to diagnostic screening, MCG has the potential to become a valuable method for surveillance monitoring of patients who have completed treatment for inflammatory cardiomyopathy. Furthermore, it could be used for treatment monitoring. While changes in the magnetic vector of the heart are not specific to inflammatory cardiomyopathy, as they may also occur in other types of cardiomyopathies, MCG offers a tool of broad and efficient diagnostic screening for cardiac pathologies without side effects.

Abstract Aims Myocardial inflammation is increasingly recognized for its association with impaired clinical outcomes in cardiac amyloidosis but a trend towards less invasive diagnosis impedes its detection. The aim of this study was to assess magnetocardiography (MCG) as a potential non-invasive method to diagnose myocardial inflammation in patients with cardiac amyloidosis. Methods and results This retrospective proof-of-concept study included 27 patients with cardiac amyloidosis who had undergone MCG and endomyocardial biopsy as part of their diagnostic workup. Immunohistopathological evaluation identified myocardial inflammation in 10 patients (37.0%). Patients with myocardial inflammation had significantly higher magnetocardiography vector (VMCG) values than those without (0.093 [IQR 0.058–0.183] vs. 0.052 [IQR 0.039–0.073]; P = 0.01). With an area under the curve of 0.785 (95% CI 0.600–0.970; P < 0.01), VMCG had significant diagnostic value for myocardial inflammation in cardiac amyloidosis when tested against a non-informative random classifier in receiver operating characteristic analysis. Youden's index identified VMCG ≥0.078 as the optimal cut-off to discriminate between patients with and without myocardial inflammation, yielding a sensitivity of 60.0%, a specificity of 88.2%, a positive predictive value of 75.0% and a negative predictive value of 78.9%. Conclusions This proof-of-concept study provides initial evidence for the potential of MCG as a non-invasive method to identify myocardial inflammation in patients with cardiac amyloidosis. These findings require validation in larger prospective studies but could substantially contribute to the optimization of personalized management in patients diagnosed with cardiac amyloidosis via non-invasive pathways in the future.

Infiltration of the myocardium with various cell types, cytokines and chemokines plays a crucial role in the pathogenesis of cardiomyopathies including inflammatory cardiomyopathies and myocarditis. A more comprehensive understanding of the precise immune mechanisms involved in acute and chronic myocarditis is essential to develop novel therapeutic approaches. This review offers a comprehensive overview of the current knowledge of the immune landscape in cardiomyopathies based on etiology. It identifies gaps in our knowledge about cardiac inflammation and emphasizes the need for new translational approaches to improve our understanding thus enabling development of novel early detection methods and more effective treatments.

BackgroundAbdominal aortic calcification (AAC) is associated with lower back pain, reduced bone mineral density of the spine. Vascular changes could also affect the already sparsely perfused intervertebral endplate and intervertebral disc. MethodsLumbar MRIs and lateral radiographs of patients with lower back pain were retrospectively analyzed. AAC was assessed on lateral lumbar radiographs according to the Kauppila score, with a maximum score of 24. Patients were grouped into no (AAC = 0), moderate (AAC 1 to ≤ 4), and severe AAC (AAC ≥ 5). Endplate and disc degeneration were classified according to the total endplate score (TEPS) and Pfirrmann classification. The associations between AAC and degenerative changes was analyzed with a generalized mixed model and was adjusted for age, sex, body mass index as well as diabetes mellitus, and smoking status.ResultsA total of 217 patients (47.9% female) were included in the analysis, totaling 1085 intervertebral levels. Of those, 45 (20.7%) patients had moderate, and 39 (18%) had severe AAC. The results of the generalized mixed model showed no aignificant association between AAC and disc degeneration (p > 0.05). In contrast, a significant positive association between AAC and the severity of TEPS (β: 0.51, 95% CI: 1.92—2.12, p = 0.004) was observed in the multivariable analysis.ConclusionsThis study demonstrates an independent association between AAC and endplate degeneration. These findings expand our knowledge about the degenerative cascade of the lumbar spine and suggest that AAC might be a modifiable risk factor for endplate changes.

BackgroundAortic abdominal calcification (AAC) is associated with spine-related conditions, such as lower back pain and reduced bone mineral density. Similar to peripheral vascular disease, AAC possibly reduces blood flow to the lumbar posterior paraspinal muscles (PPM) which may lead to atrophy and increased fatty infiltration.MethodsImaging of patients with lower back pain was analyzed. AAC was assessed on lateral lumbar radiographs according to the Kauppila classification. The cross-sectional area of the PPM was measured on a T2-weighted axial MRI sequence and the functional cross-sectional area (fCSA) and fatty infiltration (FI) were calculated with custom software. The association of AAC and FI as well as AAC and fCSA was assessed by multivariable linear regression, adjusted for age, sex, body mass index (BMI), diabetes, and smoking.ResultsTwo hundred and thirty patients (47.8% female) with a median age of 60 years (IQR 48–68) were analyzed. In patients, without AAC the median FI of the PPM was 33.3% (IQR 29.1–37.6%), compared to 44.6% (IQR 38.5–54.3%) in patients with AAC (p < 0.001). In the multivariable linear regression, both fCSA and FI of the PPM were significantly and independently associated with the degree of AAC (p = 0.037 and p = 0.015, respectively).ConclusionsThis is the first study to demonstrate a significant and independent association between AAC and PPM morphology. The results of this study improve our understanding of the interaction between AAC and spinal musculature, with AAC being a reason for atrophy of the PPM.

Climate change mitigation depends on actions that affect the public interest and lead to widespread changes in public attitudes and behavior. With the global outbreak of the COVID-19 pandemic, humanity faced a more imminent threat to its well-being and viability. This retrospective cross-sectional study examines how public interest in climate change was attenuated by the severity of the COVID-19 pandemic using Google Trends Search Volume Index (SVI), weather, and climate data on a United States state-level basis during the first two years of the pandemic from 2020 to 2022. To identify channels through which the COVID-19 pandemic affected information demand on climate change, a novel fixed effect regression model of public climate change interest was developed. The measure captures changes in the climate change SVI independent of weather and climate conditions, comprising pandemic-related changes in living circumstances such as COVID-19-related cases and deaths, mask mandates, and the proportion of the vaccinated population. Our results indicate that public interest in climate change was systematically attenuated by the severity of the COVID-19 pandemic. In addition, this study provides an approach for identifying drivers of public interest in climate change.