Self-limiting COVID‐19-associated Kikuchi‐Fujimoto disease with heart involvement: case-based review

Background The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin. Objective Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case. Methods We reviewed the literature regarding cases of “Kikuchi-Fujimoto disease (KFD)” and “COVID-19” and then “KFD” and “heart” or “myocarditis” by searching medical journal databases written in English in PubMed and Google Scholar. Results Only two cases of KFD after COVID infection have been described so far. Conclusion SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD.

Serum Organ-Specific Anti-Heart and Anti-Intercalated Disk Autoantibodies as New Autoimmune Markers of Cardiac Involvement in Systemic Sclerosis: Frequency, Clinical and Prognostic Correlates

Background: Heart involvement (HInv) in systemic sclerosis (SSc) may relate to myocarditis and is associated with poor prognosis. Serum anti-heart (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific markers of isolated autoimmune myocarditis. We assessed frequencies, clinical correlates, and prognostic impacts of AHA and AIDA in SSc. Methods: The study included consecutive SSc patients (n = 116, aged 53 ± 13 years, 83.6% females, median disease duration 7 years) with clinically suspected heart involvement (symptoms, abnormal ECG, abnormal troponin I or natriuretic peptides, and abnormal echocardiography). All SSc patients underwent CMR. Serum AHA and AIDA were measured by indirect immunofluorescence in SSc and in control groups of non-inflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141), and normal blood donors (NBD) (n = 270). AHA and AIDA status in SSc was correlated with baseline clinical, diagnostic features, and outcome. Results: The frequency of AHA was higher in SSc (57/116, 49%, p < 0.00001) than in NICD (2/160, 1%), IHF (2/141, 1%), or NBD (7/270, 2.5%). The frequency of AIDA was higher (65/116, 56%, p < 0.00001) in SSc than in NICD (6/160, 3.75%), IHF (3/141, 2%), or NBD (1/270, 0.37%). AHAs were associated with interstitial lung disease (p = 0.04), history of chest pain (p = 0.026), abnormal troponin (p = 0.006), AIDA (p = 0.000), and current immunosuppression (p = 0.01). AHAs were associated with death (p = 0.02) and overall cardiac events during follow-up (p = 0.017). Conclusions: The high frequencies of AHA and AIDA suggest a high burden of underdiagnosed autoimmune HInv in SSc. In keeping with the negative prognostic impact of HInv in SSc, AHAs were associated with dismal prognosis.

Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition

Introduction: Primary heart involvement in systemic sclerosis may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of primary heart involvement in systemic sclerosis limits our understanding and ability to focus on clinical research. We aimed to create an expert consensus definition for primary heart involvement in systemic sclerosis. Methods: A systematic literature review of cardiac involvement and manifestations in systemic sclerosis was conducted to inform an international and multi-disciplinary task force. In addition, the nominal group technique was used to derive a definition that was then subject to voting. A total of 16 clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition. Results: In total, 171 publications met eligibility criteria. Using the nominal group technique, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5–300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate (mKappa (95% CI) = 0.56 (0.46–1.00) for the first round and 0.55 (0.44–1.00) for the second round) and intra-rater agreement was good (mKappa (95% CI) = 0.77 (0.47–1.00)). Criterion validity showed a 78 (73–84)% correctness versus gold standard. Conclusion: A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research.

The Influence of Deterioration of Kidney Function on the Diagnostic Power of Laboratory Parameters Used in the Prognostic Classification of AL Amyloidosis

There is a possibility that renal dysfunction may potentially reduce the diagnostic power of the laboratory parameters Tn, NT-proBNP and sFLC levels, used in the current prognostic classification of AL amyloidosis and the diagnosis of heart involvement by amyloid. In this study, the impact of lowering the eGFR value on the usefulness of these parameters in the prognosis and diagnosis of the presence of amyloid in the myocardium was assessed in a group of 71 patients with newly diagnosed primary amyloidosis. The assessment of diagnostic power of laboratory parameters was performed on the entire study group, and in the ranges of eGFR ≥ 60 and < 60 mL/min/1.73 m2. It has been proven that, with a decrease in the eGFR value, the concentrations of NT-proBNP and the κ uninvolved light chains increase significantly (p < 0.001). To assess the diagnostic power of laboratory parameters used in the diagnosis of myocardial involvement in patients with AL amyloidosis, an ROC analysis was performed. The highest values of AUC were obtained for the NT-proBNP concentration (AUC = 0.906). The lowest values of the AUC and Youden’s index were obtained for the dFLC values (AUC = 0.723), and involved κ FLC concentration (AUC = 0.613). For all compared parameters, the smallest values of the AUC were obtained for eGFR (<60 mL/min/1.73 m2). It seems that the most suitable cardiac parameter used in the prognostic classification of AL amyloidosis, independent of renal function, is TnI. It should be noted that a concentration of involved λ chains hada higher diagnostic power to assess the heart involvement, compared to the routinely used “cardiac parameters”, TnI and NT-proBNP. It can therefore be an additional parameter used to assess the presence of amyloid in the myocardium. A decrease in eGFR value influenced the change in the diagnostic cut-off points of the most analyzed laboratory parameters. Finally, it is concluded that lowering the eGFR value reduces the utility of laboratory parameters used in the prognostic classification of AL amyloidosis.

What are the risk factors for admission to the pediatric intensive unit among pediatric patients with COVID-19?

Background Although with exceptions, evidence seems to indicate that children have lower susceptibility than adults to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When infected, children generally remain asymptomatic or develop mild disease. A small number of pediatric cases required admission to the pediatric intensive care unit (PICU), respiratory support with a mechanical ventilation and additional life-saving interventions. Even if rarely, death can occur. Aim of this manuscript is to highlight the risk factors associated with severe outcome among pediatric patients with COVID-19. Main findings Early identification of SARS-CoV-2-infected children at risk of developing severe COVID-19 is vital for service planning, as severely affected pediatric patients require high-quality care and should be followed only where an adequately structured PICU is available. However, early identification of children who must be carefully monitored for substantial risk of severe COVID-19 remains difficult. An underlying comorbidity and heart involvement are frequently observed in severe paediatric cases. Reduced left ventricular systolic function with an ejection fraction < 60%; diastolic dysfunction; and arrhythmias, including ST segment changes, QTc prolongation, and premature atrial or ventricular beat, are the earliest manifestations of heart involvement. Inclusion of heart enzyme serum levels and evaluation of ventricular function among predictive markers could lead to a more effective evaluation of children at risk with proper selection of those to admit to the PICU and with more adequate treatment in case of more severe clinical manifestations. Conclusions To appropriately manage severe pediatric COVID-19 cases, greater attention should be paid to risk factors in children and adolescents, especially to cardiovascular alterations (e.g., heart enzyme serum levels and evaluation of ventricular function). Further studies are needed and the development of a validated score based on all the most common presumed markers of disease severity seems essential.

Interleukin-1 and Systemic Sclerosis: Getting to the Heart of Cardiac Involvement

Systemic sclerosis (SSc) is rare, severe connective tissue disease characterized by endothelial and vascular damage, immune activation, and resulting in inflammation and fibrosis of skin and internal organs, including the heart. SSc is associated with high morbidity and mortality. Cardiac involvement is frequent in SSc patients, even though often asymptomatic at early stages, and represents one of the major causes of SSc-related mortality. Heart involvement has a variable clinical presentation, and its pathogenesis is not completely understood. Myocardial fibrosis is traditionally considered the immunopathologic hallmark of heart involvement in SSc. This unique histological feature is paralleled by distinctive clinical and prognostic features. The so-called “vascular hypothesis” represents the most credited hypothesis to explain myocardial fibrosis. More recently, the prominent role of an inflammatory myocardial process has been identified as a cardinal event in the evolution to fibrosis, thus also delineating an “inflammation-driven pathway to fibrosis”. The pro-inflammatory cytokine interleukin (IL)-1 has an apical and cardinal role in the myocardial inflammatory cascade and in cardiac dysfunction. The primary aim of this perspective article is: to present the emerging evidence on the role of IL-1 and inflammasome in both SSc and heart inflammation, to review the complex interplay between cellular metabolism and inflammasome activation, and to discuss the rationale for targeted inhibition of IL-1 for the treatment of SSc-heart involvement, providing preliminary experimental and clinical data to support this hypothesis.

The Role of Light Kappa and Lambda Chains in Heart Function Assessment in Patients with AL Amyloidosis

There are reports indicating that myocardial dysfunction in systemic immunoglobulin light chain amyloidosis (AL amyloidosis) stems not only from the amyloid deposit in the organ but also the cardiotoxicity of the amyloid precursor free light chains (FLCs) circulating in the blood. The aim of the study is to analyze the role of sFLC κ and λ in the assessment of heart involvement and the degree of myocardial damage in AL amyloidosis. The study involved 71 patients diagnosed with primary AL amyloidosis. The relationship between sFLC concentrations and cardiac biochemical and echocardiographic parameters was assessed. The median concentrations of N-terminal pro b-type natriuretic peptide(NT-proBNP) and troponin I (TnI) were significantly higher in patients with amyloids formed from monoclonal λ chains compared to patients with monoclonal κ proliferation. In patients with heart involvement by amyloids formed from monoclonal FLC, the study demonstrated a statistically significant positive correlation between the concentration of monoclonal antibody λ chain and TnI (R = 0.688; p < 0.05), NT-proBNP (R = 0.449; p < 0.05), and the value of diastolic dimension of the interventricular septum (IVS; R = 0.496, p < 0.05). The above data indicate that the presence of monoclonal λ chains in patients with AL amyloidosis may be associated with more severe damage to cardiomyocytes and dysfunction of the myocardium.