Left Ventricular Global Longitudinal Strain as a Parameter of Mild Myocardial Dysfunction in Athletes after COVID-19.

Whether symptoms during COVID-19 contribute to impaired left ventricular (LV) function remains unclear. We determine LV global longitudinal strain (GLS) between athletes with a positive COVID-19 test (PCAt) and healthy control athletes (CON) and relate it to symptoms during COVID-19. GLS is determined in four-, two-, and three-chamber views and assessed offline by a blinded investigator in 88 PCAt (35% women) (training at least three times per week/>20 MET) and 52 CONs from the national or state squad (38% women) at a median of two months after COVID-19. The results show that the GLS is significantly lower (GLS -18.53 ± 1.94% vs. -19.94 ± 1.42%, p < 0.001) and diastolic function significantly reduces (E/A 1.54 ± 0.52 vs. 1.66 ± 0.43, p = 0.020; E/E'l 5.74 ± 1.74 vs. 5.22 ± 1.36, p = 0.024) in PCAt. There is no association between GLS and symptoms like resting or exertional dyspnea, palpitations, chest pain or increased resting heart rate. However, there is a trend toward a lower GLS in PCAt with subjectively perceived performance limitation (p =0.054). A significantly lower GLS and diastolic function in PCAt compared with healthy peers may indicate mild myocardial dysfunction after COVID-19. However, the changes are within the normal range, so that clinical relevance is questionable. Further studies on the effect of lower GLS on performance parameters are necessary.

Echocardiographic manifestations during the first 3 months after an episode of COVID-19 and their relationship with disease severity and persistence of symptoms.

BACKGROUND: Cardiovascular manifestations in patients with COVID-19 are associated with dire outcomes. Long COVID syndrome is the persistence of symptoms after acute disease and is found in up to 40% of subjects. There is little information regarding subacute echocardiographic manifestations after COVID-19, and no study has included a Mexican mestizo population. METHODS: This cross-sectional study included subjects older than 18 with an episode of COVID-19 in the last 3 months. Those with previously known cardiovascular disease were excluded. The patient´s medical history and COVID-19 information were obtained from clinical charts. We performed a transthoracic echocardiogram in every subject and determined left ventricular (LV) index mass, LV ejection fraction (LVEF), left ventricular global longitudinal strain (LV GLS), right ventricular (RV) GLS, and tricuspid annular plane systolic excursion (TAPSE). A descriptive and comparative analysis was performed based on symptom severity and persistence. RESULTS: One hundred subjects were included; 63% were classified with mild and 37% with moderate to severe COVID-19. The median of LVEF was 60% (55-60), LV GLS and RV GLS was impaired in 34% and 74% of patients, respectively. Patients with moderate to severe disease had significantly lower LVEF (Mean Difference: -3.3), TAPSE (mean difference: -1.8), and higher (worse) LV GLS (Mean Difference: 2.5) and RV GLS (mean difference: 2.9). Persistent symptoms were associated with lower TAPSE and higher RVGLS. CONCLUSIONS: Patients who recover from COVID-19 have a high prevalence of subtle RV and LV dysfunction using GLS analysis. A moderate to severe episode was associated with worse RV and LV function measured by RV GLS, TAPSE, and LV GLS. Subjects with persistent symptoms had worse RVGLS and TAPSE.

Long-term prognostic impact of subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Cardiovascular sequelae may occur in patients recovered from coronavirus disease 2019 (COVID-19). Recent studies have detected a considerable incidence of subclinical myocardial dysfunction-assessed with speckle-tracking echocardiography-and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia. METHODS: We prospectively followed up 110 patients hospitalized at our institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 7-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization, and all-cause mortality. RESULTS: A subclinical myocardial dysfunction-defined as an impairment of left ventricular global longitudinal strain (≥-18%)-was identified at a 7-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (area under the curve: .73) and resulted in a strong independent predictor of extended MACE in multivariate regression analyses. Long-COVID condition was not associated with a worse long-term prognosis, instead. CONCLUSIONS: In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one-third of the whole population at 7-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimize the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has no prognostic relevance.

Subclinical cardiac involvement in student athletes after COVID-19 infection - Evaluation using feature tracking cardiac MRI strain analysis.

OBJECTIVES: To evaluate subclinical cardiac dysfunction in student athletes after COVID-19 infection using feature tracking cardiac MRI strain analysis. METHODS: Student athletes with history of COVID-19 infection underwent cardiac MRI as part of screening before return to competitive play. Subjects were enrolled if they had no or mild symptoms, normal cardiac MRI findings with no imaging evidence of myocarditis. Feature tracking strain analysis was performed using short and long axis cine MRI images of athletes and a separate cohort of healthy controls. Differences between the cardiac strain parameters were statistically analyzed by Mann-Whitney U test. RESULTS: The study cohort included 122 athletes (49 females, mean age 20 years ± 1.5 standard deviations) who had a history of COVID-19, and 35 healthy controls (24 females, mean age 34 years ± 18 standard deviations). COVID-19 positive athletes had normal physiologic cardiac adaptations, including significantly higher left and right ventricle end-diastolic volumes (p = 0.00001) when compared to healthy controls. There was no significant difference between biventricular ejection fraction between athletes and control subjects (p > 0.05). Cardiac MRI parameters, including left ventricle global longitudinal strain (LV-GLS), global circumferential strain (LV-GCS), and global radial strain (LV-GRS) values were normal but slightly lower in athletes compared to controls. LV-GCS and LV-GRS were significantly lower in athletes compared to controls (p = 0.007 and p = 0.005 respectively), but there was no significant difference for LV-GLS (p = 0.088). CONCLUSION: In this study of 122 athletes, there was no evidence of subclinical myocardial alterations following recovery from COVID-19 found on cardiac MRI strain analysis. When compared to healthy controls, the competitive athletes had higher end-diastolic volume indices and reduced, albeit normal, strain values of LV-GLS, LV-GCS, and LV-GRS.

Age-adjusted NT-proBNP could help in the early identification and follow-up of children at risk for severe multisystem inflammatory syndrome associated with COVID-19 (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) has emerged as a new disease associated with COVID-19 that presents in acute critically ill children with acute cardiovascular dysfunction. AIM: To determine whether the age-adjusted N-terminal pro-brain natriuretic peptide (NT-proBNP) value (Z-log-NT-proBNP) is associated with severe MIS-C and myocardial dysfunction. METHODS: A retrospective study was conducted which included children with MIS-C managed at our institution between April 1, 2020, and February 28, 2022. We divided the population into groups depending on severity based on pediatric intensive care unit (PICU) admission. We compared Z-log-NT-proBNP values across these groups and analyzed Z-log-NT-proBNP dynamics during the one-month follow-up. RESULTS: We included 17 participants [median age 3 (2-9) years] and seven (41%) required PICU admission. All (100%) of these cases presented very high (Z-log > 4) levels of NT-proBNP at the time of admission compared to only 5 (50%) patients with non-severe MIS-C (P = 0.025). NT-proBNP was significantly correlated with high-sensitive Troponin I levels (P = 0.045), Ross modified score (P = 0.003) and left ventricle ejection fraction (P = 0.021). CONCLUSION: Raised NT-proBNP, specifically very high values (Z-log-NT-proBNP > 4) could help in the early identification of MIS-C patients with myocardial dysfunction requiring inotropic support and PICU admission.

Clinico-Laboratory Profile, Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience during First and Second Waves from North India.

OBJECTIVES: To describe the clinico-laboratory profile, intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C) during the first and second waves. METHODOLOGY: This retrospective study was conducted in the paediatric emergency and paediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India involving 122 children with MIS-C admitted during the first wave (September 2020-January 2021, n = 40) and second wave (February 2021-September 2021, n = 82) of coronavirus disease 2019 (COVID-19). RESULTS: The median (interquartile range) age was 7 (4-10) years and 67% were boys. Common manifestations included fever (99%), abdominal symptoms (81%), rash (66%) and conjunctival injection (65%). Elevated C-reactive protein (97%), D-dimer (89%), procalcitonin (80%), IL-6 (78%), ferritin (56%), N-terminal pro B-type natriuretic peptide (84%) and positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody (81%) were common laboratory abnormalities. Cardiovascular manifestations included myocardial dysfunction (55%), shock (48%) and coronary artery changes (10%). The treatment included intensive care support (57%), non-invasive (33%) and invasive (18%) ventilation, vasoactive drugs (47%), intravenous immunoglobulin (IVIG) (83%), steroids (85%) and aspirin (87%). The mortality was 5% (n = 6). During the second wave, a significantly higher proportion had positive SARS-CoV-2 antibody, contact with COVID-19 and oral mucosal changes; lower markers of inflammation; lower proportion had lymphopenia, elevated IL-6 and ferritin; lower rates of shock, myocardial dysfunction and coronary artery changes; lesser need of PICU admission, fluid boluses, vasoactive drugs and IVIG; and shorter hospital stay. CONCLUSION: MIS-C is a febrile multisystemic disease characterized by hyperinflammation, cardiovascular involvement, temporal relationship to SARS-CoV-2 and good outcome with immunomodulation and intensive care. During the second wave, the severity of illness, degree of inflammation, intensive care needs, and requirement of immunomodulation were less as compared to the first wave.

Nationwide observational study of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the Czech Republic.

The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course. We performed a retrospective-prospective nationwide observational study based on patients hospitalised with PIMS-TS in CZ between 1 November 2020 and 31 May 2021. The anonymised data of patients were abstracted from medical record review. Using the inclusion criteria according to World Health Organization definition, 207 patients with PIMS-TS were enrolled in this study. The incidence of PIMS-TS out of all SARS-CoV-2-positive children was 0.9:1,000. The estimated delay between the occurrence of PIMS-TS and the COVID-19 pandemic wave was 3 weeks. The significant initial predictors of myocardial dysfunction included mainly cardiovascular signs (hypotension, oedema, oliguria/anuria, and prolonged capillary refill). During follow-up, most patients (98.8%) had normal cardiac function, with no residual findings. No fatal cases were reported.Conclusions: A 3-week interval in combination with incidence of COVID-19 could help increase pre-test probability of PIMS-TS during pandemic waves in the suspected cases. Although the parameters of the models do not allow one to completely divide patients into high and low risk groups, knowing the most important predictors surely could help clinical management.

Severe Multi-inflammatory Syndrome in Children Temporally Related to COVID 19-Clinical Course, Laboratory Profile and Outcomes from a North Indian PICU.

Objective: We describe the trajectory of clinical course, laboratory markers and outcomes in children with severe multi-inflammatory syndrome temporally related to COVID-19 (MIS-C) admitted to our pediatric intensive care unit (PICU). Methods: This was a prospective case series of children admitted to PICU between May 1, 2020 and January 31, 2021, fulfilling the case definition of MIS-C published by World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC). We analyzed demographic, clinical, laboratory data and echocardiographic findings. We also plotted the variation in trends between survivors and nonsurvivors. Results: Of the 34 critically ill children referred to PICU with diagnosis of MIS-C only 17 fulfilled the WHO/CDC classification of MIS-C, rest were MISC mimickers albeit other tropical infections. Median age at admission was 4 years (range 1y 6 mo-8 years). Fever, rash and conjunctival redness were most prominent symptoms. Myocardial involvement was seen in 70.5% while 76.4% developed shock; Invasive mechanical ventilation was required in 64.7% cases. Inflammatory markers showed a downward trend such as-median C- reactive protein (mg/L) had a serial reduction in levels-from (median/IQR) 210 (132.60, 246.90) at admission to 52.3 (42, 120) on Day 3. Median Ferritin (ng/ml) (n = 12) was 690 (203, 1324), serum LDH (IU/L) (n = 12) was 505 (229.5, 1032) and Mean D-dimer (ng/ml) (n = 7) was 5093.85 (1991.65), suggestive of hyperinflammatory syndrome. Twelve patients received intravenous immune globulin, with adjunctive steroid therapy used in two third of the cases. Six children died, 4 of them were under-5 years of age. Tocilizumab was prescribed in two children with high vasotrope inotrope score (VIS), cardiogenic shock and oxygenation index more than 15, both survived. Conclusions: Severe MIS-C has a heterogenous presentation, local or regional outbreaks of prevalent infectious diseases often lead to confusion and overdiagnosis. Higher proportion of mortality was seen in Under -5 children with MISC. Shock-like presentation, presence of myocardial dysfunction or nonsurvivor status is associated with higher trend of inflammatory markers and more profound multi-organ dysfunction. If disease progresses rapidly despite first line therapy (IvIg and steroids), use of Tocilizumab should be considered-as a rescue therapy under resource limitations in the absence of extracorporeal support.

Point-of-care detection of myocardial injury, a pre-clinical study

Evaluation of myocardial function is critical in severe inflammations as myocarditis, COVID-19 and sepsis, since it can lead to organ failure and death. Point-of-care detection of myocardial injury may improve the treatment of these critically ill patients. The study aimed to develop point of care technology for assessing the systolic and diastolic cardiac functions in animal model of systemic inflammation. Ultrasound and ventricular pressure were continuously recorded in Langendorff perfused isolated adult rat hearts. A computer controlled system controlled the ventricle loading conditions. The preload of both ventricles swung in a sinusoidal manner between target values of 2 and 22 mmHg. Collagenase (MMP8) was added to the Krebs-Henseleit solution following baseline recordings, to emulate the release of MMPs from activated leukocytes and macrophages. Collagenase perfusion led to gradual decline in peak systolic pressure and decrease in the end-diastolic volume (EDV), that were associated with concentric myocardial wall thickening. Extracellular matrix degradation by collagenases caused sever diastolic dysfunction with overt shift of the end-diastolic volume toward lower volumes, without significant changes in the epicardial diameter. Early detection of these signs may assist in assessing the severity of the myocardial injury and prompt the adequate treatment. © 2021 IEEE.

Cardiac manifestations and short-term outcomes of multisystem inflammatory syndrome in Middle Eastern children during the COVID-19 pandemic: a case series.

We herein report on a series of four patients presented to our tertiary care centre with features of multisystem inflammatory syndrome in children and cardiac involvement. Two of our patients had recent exposure to a COVID-19-positive patient, one had recent documented infection, and another had no known positive contact. All the patients were tested positive for severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibody at the time of presentation. All of them fulfilled the diagnostic criteria according to the World Health Organization Centers for Disease Control or the British guidelines for MIS-C (fever for ≥3 days, multisystem involvement (at least two), elevated markers of inflammation, and no other alternative diagnosis).Cardiac involvement was variable ranging from isolated ectasia of the coronary arteries to full-blown pancarditis such as severe biventricular dysfunction, multi-valvar involvement, and pericardial effusion.All our patients received intravenous immunoglobulin (2 g/kg), methylprednisolone, and aspirin and some required inotropic support and ICU admission.Remarkably, all our patients showed significant improvement in their cardiac disease within a few days as evident on serial echocardiographic evaluation. However, we stress the need for long-term follow-up as one of our patients demonstrated mild LV myocardial scarring as evident by gadolinium late enhancement on a cardiac MRI.

The role and efficacy of routine high-sensitivity troponin T screening in paediatric COVID-19.

OBJECTIVE: We aimed to evaluate the efficacy and role of high-sensitivity troponin T in children with a confirmed SARS-CoV-2 infection and also the correlation of troponin T levels with symptoms, and echocardiographic findings were analysed. METHODS: Two hundred and fourteen patients with a confirmed SARS-CoV-2 infection between the dates of 28 March and 15 August 12020 were enrolled in this retrospective single-centre study. Patients with comorbidities and diagnosed as multisystem inflammatory syndrome in children were excluded. Demographic data, clinical and laboratory parameters were evaluated. The patients were classified and compared according to the troponin positivity. The correlation of troponin T with symptoms and echocardiographic findings was analysed. RESULTS: The most common symptoms in the whole study group were fever (53.3%) and cough (24.8%). Troponin T levels were elevated in 15 (7%) patients. The most common symptom in patients with troponin positivity was also fever (73.3%). Troponin T positivity was significantly higher in patients under the age of 12 months and troponin T levels were negatively correlated with age. C-reactive protein levels were elevated in 77 (36%) of the patients in the whole group and 7 (46.7%) of 15 patients with troponin positivity. C-reactive protein levels were similar between groups. CONCLUSION: Routine troponin screening does not yield much information in previously healthy paediatric COVID-19 patients without any sign of myocardial dysfunction. Elevated troponin levels may be observed but it is mostly a sign of myocardial injury without detectable myocardial dysfunction in this group of patients.

Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production.

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1ß, and CXCL2.

Cardiac involvement in patients recovered from COVID-19 identified using left ventricular longitudinal strain.

INTRODUCTION: Coronavirus disease-19 (COVID-19) has been associated with subclinical myocardial dysfunction during its acute phase and a recurring pattern of reduced basal left ventricular longitudinal strain on speckle-tracking echocardiography (STE) in hospitalized patients. But a question still remains unanswered: speckle-tracking echocardiography might also be suitable to detect residual myocardial involvement after acute stage of COVID-19? METHODS AND RESULTS: We studied 100 patients recovered from COVID-19 with STE to evaluate global (GLS) and segmentar longitudinal strain (LS) and compared with a control group of 100 healthy individuals. STE was performed at a median of 130.35 ± 76.06 days after COVID-19 diagnostic. Demographic and echocardiographic parameters are similar in both groups. Left ventricular ejection faction (LVEF) and GLS were normal in COVID-19 patients (66.20 ± 1.98% and - 19.51 ± 2.87%, respectively). A reduction in mean LS for the basal segments was found in COVID-19 (16.48 ± 5.41%) when compared to control group (19.09 ± 4.31%) (p < 0.001). CONCLUSION: The present study suggests that COVID-19-induced cardiac involvement could persist after recovery of the disease and may be detected by deformation abnormalities using STE. COVID-19-induced myocardial involvement often shows specific LV deformation patterns due to pronounced edema and/or myocardial damage in basal LV segments.

Evolution of right and left ventricle routine and speckle-tracking echocardiography in patients recovering from coronavirus disease 2019: a longitudinal study.

AIMS: We aim to assess changes in routine echocardiographic and longitudinal strain parameters in patients recovering from Coronavirus disease 2019 during hospitalization and at 3-month follow-up. METHODS AND RESULTS: Routine comprehensive echocardiography and STE of both ventricles were performed during hospitalization for acute coronavirus disease 2019 (COVID-19) infection as part of a prospective pre-designed protocol and compared with echocardiography performed ∼3 months after recovery in 80 patients, using a similar protocol. Significantly improved right ventricle (RV) fractional area change, longer pulmonary acceleration time, lower right atrial pressure, and smaller RV end-diastolic and end-systolic area were observed at the recovery assessment (P < 0.05 for all). RV global longitudinal strain improved at the follow-up evaluation (23.2 ± 5 vs. 21.7 ± 4, P = 0.03), mostly due to improvement in septal segments. Only eight (10%) patients recovering from COVID-19 infection had abnormal ejection fraction (EF) at follow-up. However, LV related routine (E, E/e', stroke volume, LV size), or STE parameters did not change significantly from the assessment during hospitalization. A significant proportion [36 (45%)] of patients had some deterioration of longitudinal strain at follow-up, and 20 patients (25%) still had abnormal LV STE ∼3 months after COVID-19 acute infection. CONCLUSION: In patients previously discharged from hospitalization due to COVID-19 infection, RV routine echocardiographic and RV STE parameters improve significantly concurrently with improved RV haemodynamics. In contrast, a quarter of patients still have LV systolic dysfunction based on STE cut-offs. Moreover, LV STE does not improve significantly, implying subclinical LV dysfunction may be part and parcel of recovering from COVID-19 infection.

Decrease of left ventricular ejection fraction in severe illness patients due to COVID-19 may improve as the disease resolves

Background/aim: Increase in publications supporting myocardial involvement in the COVID-19 disease has led to need to gain insight into the the global burden of heart failure after pandemic. We examined the course of myocardial systolic function in patients without elevated troponin levels. Materials and methods: We performed a prospective study. Patients with high troponin levels were excluded from the study in order to definitively exclude complications known to cause permanent left ventricular systolic dysfunction, such as acute coronary syndromes. Two echocardiographic examinations were performed. The first evaluation was performed within the days of hospitalization, if possible, on the day when dyspnea is severe. The second evaluation was performed during the outpatient clinic controls one month after the patient was recovered. Left ventricular ejection fraction (LVEF) was measured using the biplane method of disks (modified Simpson's rule). Results: In the first evaluation, LVEF was found to be significantly lower in the severe illness group than mild/moderate illness group (50 ± 6% and 59 ± 6%; p = 0.03). LVEF decrease (<50%) was found in fifteen patients (43 ± 4%) and detected as global hypokinesia but not segmental. All of these patients were in the severe illness group. In the second evaluation, LVEFs of the fifteen patients with decreased LVEF in the first evaluation were improved and detected in normal limits (first evaluation = 43 ± 4% and second evaluation = 55 ± 2%, p = 0.01). Conclusion: Considering patients without elevated troponin levels during COVID-19 infection, no permanent systolic dysfunction was detected after first month of recovery. We found that transient myocardial dysfunction may develop in the severe illness group with normal troponin levels, LVEF may decrease in the acute phase and improve with the recovery period.

Hidden danger of COVID-19 outbreak: evaluation of subclinical myocardial dysfunction in patients with mild symptoms.

The COVID-19 infection, which is caused by the novel coronavirus SARS-CoV-2, has rapidly emerged as a global public health issue. Cardiac complications secondary to this infection are common and associated with mortality. This study aimed to evaluate whether subclinical myocardial dysfunction exists in non-hospitalized mildly symptomatic COVID-19 patients using left ventricular global longitudinal strain (LVGLS). In this cross-sectional, single-center study, data were collected from non-hospitalized mildly symptomatic COVID-19 patients between January 01 and February 01, 2021. Fifty (26 male, 24 female) COVID-19 patients and 50 age- and sex-matched healthy volunteers were included in the study. Apical four-, three-, and two-chamber images were analyzed longitudinally by conventional methods and speckle tracking echocardiography (STE) for left ventricle functions. The mean age of the COVID-19 patients was 39.5 ± 8.96, and 52% of them were male. The most prevalent presenting symptoms were fever [in 34 (68%)], asthenia [in 30 (60%)], loss of appetite [in 21 (42%)], myalgia [in 20 (40%)], and cough [in 13 (26%)]. Plasma levels of C-reactive protein (CRP) were significantly higher in the COVID-19 patients than in the controls (10.84 ± 12.44 vs. 4.50 ± 2.81, p < 0.001). There was no significant difference between the groups in terms of standard echocardiography and Doppler parameters (p > 0.05). Left ventricular longitudinal strain and strain velocity parameters were significantly decreased in COVID-19 patients compared to healthy individuals. LV-GLS values (- 21.72 ± 3.85% vs. - 23.11 ± 4.16%; p = 0.003) were significantly lower in COVID-19 patients compared with the healthy controls. Mildly symptomatic COVID-19 patients also have subclinical myocardial dysfunction similar to hospitalized patients. STE has the potential for detecting subclinical LV systolic dysfunction, and can provide useful information regarding cardiac status in mildly symptomatic COVID-19 population.

Intracranial Hypertension in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is characterized by fever and multiorgan system dysfunction. Neurologic complications of MIS-C are not well described. We present 4 patients with MIS-C who had intracranial hypertension and discuss the unique management considerations when this occurs concurrently with significant myocardial dysfunction.

Cardiac manifestations in SARS-CoV-2-associated multisystem inflammatory syndrome in children: a comprehensive review and proposed clinical approach.

Initial reports on COVID-19 described children as largely spared from severe manifestations, with only 2-6% of children requiring intensive care treatment. However, since mid-April 2020, clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID-19 have been reported. This condition was named as SARS-Cov-2-associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease. Here, we present a narrative review of cases reported in literature and we discuss the clinical acute and follow-up management of these patients. Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes. Elevated inflammatory markers and evidence of cytokine storm were frequently observed. A subset of these patients also presented with hypotension and shock (20-100%) from either acute myocardial dysfunction or systemic hyperinflammation/vasodilation. Coronary artery dilation or aneurysms have been described in 6-24%, and arrhythmias in 7-60%. Cardiac support, immunomodulation, and anticoagulation are the key aspects for the management of the acute phase. Long-term structured follow-up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations.Conclusion: Multisystem inflammatory syndrome is a novel syndrome related to SARS-CoV-2 infection. Evidence is still scarce but rapidly emerging in the literature. Cardiac manifestations are frequent, including myocardial and coronary involvement, and need to be carefully identified and monitored over time. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2. What is New: • Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock. • Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias. • Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation. • Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.

Prominent Longitudinal Strain Reduction of Basal Left Ventricular Segments in Patients With Coronavirus Disease-19.

BACKGROUND: Coronavirus disease-19 (COVID-19) has been associated with overt and subclinical myocardial dysfunction. We observed a recurring pattern of reduced basal left ventricular (LV) longitudinal strain on speckle-tracking echocardiography in hospitalized patients with COVID-19 and subsequently aimed to identify characteristics of affected patients. We hypothesized that patients with COVID-19 with reduced basal LV strain would demonstrate elevated cardiac biomarkers. METHODS AND RESULT: Eighty-one consecutive patients with COVID-19 underwent speckle-tracking echocardiography. Those with poor quality speckle-tracking echocardiography (n = 2) or a known LV ejection fraction of <50% (n = 4) were excluded. Patients with an absolute value basal longitudinal strain of <13.9% (2 standard deviations below normal) were designated as cases (n = 39); those with a basal longitudinal strain of ≥13.9% were designated as controls (n = 36). Demographics and clinical variables were compared. Of 75 included patients (mean age 62 ± 14 years, 41% women), 52% had reduced basal strain. Cases had higher body mass index (median 34.1; interquartile range 26.5-37.9 kg/m2 vs median 26.9, interquartile range, 24.8-30.0 kg/m2, P = .009), and greater proportions of Black (74% vs 36%, P = .0009), hypertensive (79% vs 56%, P = .026), and diabetic patients (44% vs 19%, P = .025) compared with controls. Troponin and N-terminal pro-brain natriuretic peptide levels trended higher in cases, but were not significantly different. CONCLUSIONS: Reduced basal LV strain is common in patients with COVID-19. Patients with hypertension, diabetes, obesity, and Black race were more likely to have reduced basal strain. Further investigation into the significance of this strain pattern is warranted.

Cardiovascular impact of COVID-19 with a focus on children: A systematic review.

BACKGROUND: Since the beginning of the pandemic, coronavirus disease-2019 (COVID-19) in children has shown milder cases and a better prognosis than adults. Although the respiratory tract is the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection in adults. AIM: To summarize the current knowledge about the potential cardiovascular involvement in pediatric COVID-19 in order to give a perspective on how to take care of them during the current pandemic emergency. METHODS: Multiple searches in MEDLINE, PubMed were performed using the search terms "COVID-19" or "SARS-CoV-2" were used in combination with "myocardial injury" or "arrhythmia" or "cardiovascular involvement" or "heart disease" or "congenital heart disease" or "pulmonary hypertension" or "long QT" or "cardiomyopathies" or "channelopathies" or "Multisystem inflammatory system" or "PMIS" or "MIS-C" or "Pediatric multisystem inflammatory syndrome" or "myocarditis" or "thromboembolism to identify articles published in English language from January 1st, 2020 until July 31st, 2020. The websites of World Health Organization, Centers for Disease control and Prevention, and the Johns Hopkins Coronavirus Resource Center were reviewed to provide up to date numbers and infection control recommendations. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts concerning the subject were reviewed by the authors, and the data were extracted using a standardized collection tool. Data were subsequently analyzed with descriptive statistics. For Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19 (PMIS), multiple meta-analyses were conducted to summarize the pooled mean proportion of different cardiovascular variables in this population in pseudo-cohorts of observed patients. RESULTS: A total of 193 articles were included. Most publications used in this review were single case reports, small case series, and observational small-sized studies or literature reviews. The meta-analysis of 16 studies with size > 10 patients and with complete data about cardiovascular involvement in children with PMIS showed that PMIS affects mostly previously healthy school-aged children and adolescents presenting with Kawasaki disease-like features and multiple organ failure with a focus on the heart, accounting for most cases of pediatric COVID-19 mortality. They frequently presented cardiogenic shock (53%), ECG alterations (27%), myocardial dysfunction (52%), and coronary artery dilation (15%). Most cases required PICU admission (75%) and inotropic support (57%), with the rare need for extracorporeal membrane oxygenation (4%). Almost all of these children wholly recovered in a few days, although rare deaths have been reported (2%). Out of PMIS cases we identified 10 articles reporting sporadic cases of myocarditis, pulmonary hypertension and cardiac arrythmias in previously healthy children. We also found another 10 studies reporting patients with pre-existing heart diseases. Most cases consisted in children with severe COVID-19 infection with full recovery after intensive care support, but cases of death were also identified. The management of different cardiac conditions are provided based on current guidelines and expert panel recommendations. CONCLUSION: There is still scarce data about the role of cardiovascular involvement in COVID-19 in children. Based on our review, children (previously healthy or with pre-existing heart disease) with acute COVID-19 requiring hospital admission should undergo a cardiac workup and close cardiovascular monitoring to identify and treat timely life-threatening cardiac complications.