Left atrial stiffness and strain are novel indices of left ventricular diastolic function in children: validation followed by application in multisystem inflammatory syndrome in children due to COVID-19.

AIMS: We hypothesized left atrial (LA) stiffness may serve as a surrogate marker in children to differentiate elevated pulmonary capillary wedge pressure (PCWP) from normal and help detect diastolic dysfunction in myocardial injury due to multisystem inflammatory syndrome in children (MIS-C). METHODS AND RESULTS: We validated LA stiffness in 76 patients (median age 10.5 years), 33 had normal PCWP (<12 mmHg) and 43 had elevated PCWP (≥12 mmHg). LA stiffness was applied to 42 MIS-C patients [28 with myocardial injury (+) and 14 without myocardial injury (-)], defined by serum biomarkers. The validation group consisted of a group with and without cardiomyopathies, whose PCWP values ranged from normal to severely elevated. Peak LA strain was measured by speckle-tracking and E/e' from apical four chamber views. Noninvasive LA stiffness was calculated as: LAStiffness=E/e'LAPeakStrain (%-1). Patients with elevated PCWP showed significantly elevated LA stiffness [median 0.71%-1 vs. 0.17%-1, P < 0.001]. Elevated PCWP group showed significantly decreased LA strain (median: 15.0% vs. 38.2%, P < 0.001). Receiver operator characteristic (ROC) curve for LA stiffness yielded an area under the curve (AUC) of 0.88 and cutoff value of 0.27%-1. In MIS-C group, ROC curve yielded an AUC of 0.79 and cutoff value of 0.29%-1 for identifying myocardial injury. CONCLUSION: In children with elevated PCWP, LA stiffness was significantly increased. When applied to children with MIS-C, LA stiffness classified myocardial injury accurately. LA stiffness and strain may serve as noninvasive markers of diastolic function in the pediatric population.

Outcomes of pediatric lupus care delivery in an electronic health record-based pediatric lupus registry

618 Table 2Factors associated with timely outpatient rheumatology follow-up RR 95% CI p-value Month of fol ow-up 0.99 [0.98 - 1.00] 0.09 Post-MOC 1.09 [0.93 - 1.28] 0.29 Age at visit 0.97 [0.94 – 1.00] 0.09 Male sex 0.92 [0.73 - 1.16] 0.49 Race/ethnicity  Reference: Non-Hispanic White -  Asian alone or in combination 1.20 [0.91 - 1.58] 0.19  Black alone or in combination 1.22 [0.92 - 1.62] 0.17  Hispanic White/Other 1.51 [1.15 - 1.99] 0.00  Non-Hispanic Other race 0.54 [0.28 - 1.02] 0.06 Social Vulnerability Index  Lowest  Medium Low 1.00 [0.75 - 1.33] 0.98  Medium High 0.94 [0.71 - 1.25] 0.68  Highest 1.03 [0.82 - 1.29] 0.82 Within 6 months of diagnosis at last visit 1.26 [1.05 - 1.53] 0.02 Prednisone use at last visit 1.17 [0.93 - 1.46] 0.17 SLEDAI score at last visit 1.02 [1.01 - 1.04] 0.01 Any DMARD use at last visit 1.52 [1.04 - 2.24] 0.03 History of synovitis 0.85 [0.70 - 1.05] 0.13 History of lupus nephritis 1.13 [0.95 - 1.35] 0.17 Estimates from modified robust Poisson models with subject-level random effects

Skewed Cytokine Responses Rather Than the Magnitude of the Cytokine Storm May Drive Cardiac Dysfunction in Multisystem Inflammatory Syndrome in Children.

Background Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS-C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine milieu, microangiopathy, or severity of shock. Methods and Results We analyzed echocardiographic parameters of myocardial deformation and compared global and segmental left ventricular strain between 43 cases with MIS-C ≤18 years old and 40 controls. Primary outcomes included left ventricular global longitudinal strain, right ventricular free wall strain), and left atrial strain. We evaluated relationships between strain and profiles of 10 proinflammatory cytokines, microangiopathic features (soluble C5b9), and vasoactive-inotropic requirements. Compared with controls, cases with MIS-C had significant impairments in all parameters of systolic and diastolic function. 65% of cases with MIS-C had abnormal left ventricular function (|global longitudinal strain|<17%), although elevations of cytokines were modest. All left ventricular segments were involved, without apical or basal dominance to suggest acute stress cardiomyopathy. Worse global longitudinal strain correlated with higher ratios of interleukin-6 (ρ -0.43) and interleukin-8 (ρ -0.43) to total hypercytokinemia, but not absolute levels of interleukin-6 or interleukin-8, or total hypercytokinemia. Similarly, worse right ventricular free wall strain correlated with higher relative interleukin-8 expression (ρ -0.59). There were no significant associations between function and microangiopathy or vasoactive-inotropic requirements. Conclusions Myocardial function is globally decreased in MIS-C and not explained by acute stress cardiomyopathy. Cardiac dysfunction may be driven by the relative skew of the immune response toward interleukin-6 and interleukin-8 pathways, more so than degree of hyperinflammation, refining the current paradigm of myocardial involvement in MIS-C.