The inflammatory spectrum of cardiomyopathies.

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.

Case report: Recurrence of inflammatory cardiomyopathy detected by magnetocardiography.

Background: The 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 presentation: A 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. Conclusion: In 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.

Case report: Magnetocardiography as a potential method of therapy monitoring in amyloidosis.

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.

Application of Magnetocardiography to Screen for Inflammatory Cardiomyopathy and Monitor Treatment Response.

Background Inflammatory cardiomyopathy is one of the most common causes of sudden cardiac death in young adults. Diagnosis of inflammatory cardiomyopathy remains challenging, and better monitoring tools are needed. We present magnetocardiography as a method to diagnose myocardial inflammation and monitor treatment response. Methods and Results A total of 233 patients were enrolled, with a mean age of 45 (±18) years, and 105 (45%) were women. The primary analysis included 209 adult subjects, of whom 66 (32%) were diagnosed with inflammatory cardiomyopathy, 17 (8%) were diagnosed with cardiac amyloidosis, and 35 (17%) were diagnosed with other types of nonischemic cardiomyopathy; 91 (44%) did not have cardiomyopathy. The second analysis included 13 patients with inflammatory cardiomyopathy who underwent immunosuppressive therapy after baseline magnetocardiography measurement. Finally, diagnostic accuracy of magnetocardiography was tested in 3 independent cohorts (total n=23) and 1 patient, who developed vaccine-related myocarditis. First, we identified a magnetocardiography vector to differentiate between patients with cardiomyopathy versus patients without cardiomyopathy (vector of ≥0.051; sensitivity, 0.59; specificity, 0.95; positive predictive value, 93%; and negative predictive value, 64%). All patients with inflammatory cardiomyopathy, including a patient with mRNA vaccine-related myocarditis, had a magnetocardiography vector ≥0.051. Second, we evaluated the ability of the magnetocardiography vector to reflect treatment response. We observed a decrease of the pathologic magnetocardiography vector toward normal in all 13 patients who were clinically improving under immunosuppressive therapy. Magnetocardiography detected treatment response as early as day 7, whereas echocardiographic detection of treatment response occurred after 1 month. The magnetocardiography vector decreased from 0.10 at baseline to 0.07 within 7 days (P=0.010) and to 0.03 within 30 days (P<0.001). After 30 days, left ventricular ejection fraction improved from 42.2% at baseline to 53.8% (P<0.001). Conclusions Magnetocardiography has the potential to be used for diagnostic screening and to monitor early treatment response. The method is valuable in inflammatory cardiomyopathy, where there is a major unmet need for early diagnosis and monitoring response to immunosuppressive therapy.

Epidemiological Impact of Myocarditis.

Myocarditis is an inflammatory disease of the heart muscle with a wide range of potential etiological factors and consequently varying clinical patterns across the world. In this review, we address the epidemiology of myocarditis. Myocarditis was considered a rare disease until intensified research efforts in recent decades revealed its true epidemiological importance. While it remains a challenge to determine the true prevalence of myocarditis, studies are underway to obtain better approximations of the proportions of this disease. Nowadays, the prevalence of myocarditis has been reported from 10.2 to 105.6 per 100,000 worldwide, and its annual occurrence is estimated at about 1.8 million cases. This wide range of reported cases reflects the uncertainty surrounding the true prevalence and a potential underdiagnosis of this disease. Since myocarditis continues to be a significant public health issue, particularly in young adults in whom myocarditis is among the most common causes of sudden cardiac death, improved diagnostic and therapeutic procedures are necessary. This manuscript aims to summarize the current knowledge on the epidemiology of myocarditis, new diagnostic approaches and the current epidemiological impact of the COVID-19 pandemic.

Antimicrobial and Immune-Modulatory Effects of Vitamin D Provide Promising Antibiotics-Independent Approaches to Tackle Bacterial Infections - Lessons Learnt from a Literature Survey.

Antimicrobial multidrug-resistance (MDR) constitutes an emerging threat to global health and makes the effective prevention and treatment of many, particularly severe infections challenging, if not impossible. Many antibiotic classes have lost antimicrobial efficacy against a plethora of infectious agents including bacterial species due to microbial acquisition of distinct resistance genes. Hence, the development of novel anti-infectious intervention strategies including antibiotic-independent approaches is urgently needed. Vitamins such as vitamin D and vitamin D derivates might be such promising molecular candidates to combat infections caused by bacteria including MDR strains. Using the Pubmed database, we therefore performed an in-depth literature survey, searching for publications on the antimicrobial effect of vitamin D directed against bacteria including MDR strains. In vitro and clinical studies between 2009 and 2019 revealed that vitamin D does, in fact, possess antimicrobial properties against both Gram-positive and Gram-negative bacterial species, whereas conflicting results could be obtained from in vivo studies. Taken together, the potential anti-infectious effects for the antibiotic-independent application of vitamin D and/or an adjunct therapy in combination with antibiotic compounds directed against infectious diseases such as tuberculosis, H. pylori infections, or skin diseases, for instance, should be considered and further investigated in more detail.