The Effect Of Rhabdomyomas On Underlying Cardiomyopathy: A Case Report

Case Presentation: Term male infant born to SARS-CoV-2 positive mother with infant testing negative. ECG for perinatal bradycardia revealed ventricular pre-excitation. Echocardiogram showed asymmetric LV hypertrophy with prominent trabeculations, subaortic narrowing with no pressure gradient, and normal biventricular systolic function. Rapid increase in RV pressure estimates and NT-proBNP in first week if life concerning for diastolic dysfunction. Anti-arrhythmic therapy initiated for SVT with subsequent resolution. Later, developed progressive LV dilation and systolic dysfunction. Myocardium showed regions resembling non-compaction and others concerning for infiltrative process. Cardiac MRI showed no obvious tumors, but rhabdomyomas could not be ruled out given similar appearance to myocardium. Due to worsening heart failure, everolimus therapy initiated to target potential rhabdomyomas while awaiting genetic testing for tuberous sclerosis. Subaortic narrowing and LV hypertrophy improved within days, and LV appearance became more consistent with non-compaction. Genetic testing revealed a TSC2 gene variant consistent with tuberous sclerosis. Systolic function improved, and patient discharged on afterload reduction. Echocardiogram 6 months post-discharge shows continued LV dilation and mild systolic dysfunction. Discussion(s): Although outflow obstruction and arrhythmias are common with cardiac rhabdomyomas and can cause dysfunction, our patient developed progressive dysfunction in the absence of outflow tract gradient or prolonged arrhythmia. As rhabdomyomas subsided, it became clearer that he had an underlying cardiomyopathy. We suspect that rhabdomyomas in the setting of abnormal myocardium led to abnormalities in myocardial contractility and compliance causing combined systolic and diastolic dysfunction. After complete resolution of rhabdomyomas, cardiac function has improved. However, he continues to have ventricular dilation and mild dysfunction attributable to cardiomyopathy. It is unlikely that mother's SARS-CoV-2 infection played a role as infant tested negative and clinical picture was not consistent with myocarditis.

Multisystemic inflammatory syndrome of the adult post-COVID-19.

BACKGROUND: Multisystemic inflammatory syndrome of the adult, a new condition associated with an irregular immune response similar to that of children, is characterized by shock, heart failure or persistent hypotension, dyspnea on exertion, mild-moderate hypoxemia, gastric symptoms and elevated markers of systemic inflammation after severe COVID-19 pneumonia. CLINICAL CASE: A 56-year-old patient, uncontrolled diabetic, who presented symptoms associated with dyspnea, desaturation, chest pain and persistent fever, previously with severe pneumonia after one month of treatment. He was treated with oxygen, steroids and antibiotics for 3 weeks, but his symptoms worsened and he developed severe orthopnea, hypotension, chest pain, dyspnea at rest and severe desaturation, as well as elevation of inflammation markers (C-reactive protein, ESR, D-dimer, ferritin). Tomography of the chest showed residual pneumonia based on consolidation and ground glass. Echocardiogram evidenced diastolic dysfunction, myopericarditis and secondary endocarditis. Multisystemic inflammatory syndrome of the adult was diagnosed and patient was treated with IV immunoglobulin and steroid with a favorable response to treatment. CONCLUSION(S): This case shows that the adult systemic inflammatory syndrome is a differential diagnosis in a patient with shock of unknown etiology, heart failure and severe dyspnea previously infected by SARS-CoV-2. Immunoglobulin and steroid are the effective first-line treatment with excellent clinical response.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Echocardiographic assessment of left ventricular structure and function in hypertensive disorders of pregnancy at six months and two years postpartum

Purpose: Hypertensive disorders of pregnancy (HDP) are associated with longer term postpartum cardiovascular sequelae, including double the risk of ischaemic heart disease and cardiovascular mortality (1). Transthoracic echocardiograms (TTE) were performed in women with pregnancies complicated by gestational hypertension and pre-eclampsia, or uncomplicated pregnancy, at six months and two years postpartum. The aim was to longitudinally assess cardiac structure and function in women with HDP and compare this to women who had a normotensive pregnancy. The six-month results have been previously reported, we now present the two-year data. Method(s): A prospective cohort study was conducted in a pre-specified subgroup of 126 patients within a single, tertiary referral centre as part of the P4 (Post Partum, Physiology, Psychology, and Paediatric Follow Up) study (2). 74 (59%) women had a normotensive pregnancy, and 52 (41%) had a pregnancy complicated by HDP. Women with pre-existing hypertension were excluded from the study. The mean patient age at time of six-month postpartum TTE was 32 years (range 22-47 years). TTEs were performed by blinded experienced sonographers and reported by a single blinded imaging cardiologist. Result(s): Six months postpartum. 126 women underwent TTE at six months postpartum. Although all results fell within normal ranges, compared to women with a normotensive pregnancy, those with HDP had increased left ventricle (LV) wall thickness, higher relative wall thickness, and increased LV mass. E/A ratio was lower, and E/E' ratios higher in the group with pregnancy complicated by HDP, indicating a trend towards poorer diastolic function (2,3). Two years postpartum. 35 women completed a two year postpartum TTE (18 normotensive, 17 HDP). Measurements fell within normal ranges in both groups of women. At two years postpartum, women with HDP had larger BSA (1.9 vs 1.71 2 p=0.003), larger LV internal diastolic diameter (48.4 vs 45.5mm p=0.017) and increased inter-ventricular septum thickness (8.5 vs 7.7mm p=0.007) compared to those with normotensive pregnancy. LV mass was greater in women with HDP (98.1 vs 81.5g), as was LA volume indexed (25.4 vs 23.4 cm3/m3), however these differences did not reach significance (p=0.053 and 0.196 respectively). Compared to normotensive women, those with HDP had higher septal (8.7 vs 7.3 p=0.014) and lateral (6.6 vs 5.4 p=0.017) E/E' ratios, indicating a trend towards diastolic dysfunction. Conclusion(s): Despite measurements falling within normal ranges, our results indicate that women with HDP have changes in cardiac structure and function that persist out to two years postpartum. Limitations exist due to incomplete follow up, leading to small sample size;this was partially due to restrictions on service provision in the context of the COVID-19 pandemic. (Table Presented).

Echocardiographic phenotype in severe aortic valve stenosis with and without cardiac amyloidosis: The AMY-TAVI trial

Background: Longitudinal Strain (LS) pattern in cardiac amyloidosis (CA) typically spares the apex of the heart, which is a sensitive and specific finding that can be used to distinguish CA from other causes of left ventricular (LV) hypertrophy. RELAPS >1 suggests with high specificity CA, and shows a bright red in the apical segments of the polar map. Purpose(s): To identify differential echocardiographic characteristics of aortic stenosis (AS) with concomitant TTR-CA (AS-CA) compared to AS alone. Method(s): Patients with severe symptomatic AS undergoing TAVI were prospectively and consecutively included between Jan-19 and Dec-20. Pre-procedure, a complete echocardiogram was performed that included deformation parameters using Speckle-Tracking. Strain derived Indices accepted for CA screening were calculated: RELAPS: Relative apical LS (average apical LS/average basal+mid LS);SAB: (apical-septal/basal-septal LS);EFSR: (LVEF/GLS). After TAVI, a 99Tc-DPD scintigraphy and a proteinogram were performed to screen for CA. Result(s): 324 patients were included. The mean age was 81 yo, 52% women. 39 (12%) patients presented cardiac uptake on scintigraphy: 14 (4.3%) grade 1;13 (4%) grade 2, and 11 (3.4%) grade 3. Strain analysis could be performed in 243 patients due to acoustic window and covid19 pandemic restrictions. Echocardiographic characteristics between AS alone and those with grade 1 (AS-DTD1) and grade 2/3 (AS-CA) are shown in Table 1. Compared with AS alone, patients with AS-CA had significantly lower transvalvular gradients, although similar AVA, and low flow-low gradient (LF-LG) AS was more prevalent. AS-CA exhibited slightly worse cardiac remodeling (LV mass ind: 202 g/m2 vs 176 g/m2, p=0.032), and worse diastolic dysfunction, but without significant differences in thickness, diameters or volumes, with similar relative wall thickness (RWT: 0.53 vs. 0.51 mm, p=0.52). LVEF was similar, however myocardial contraction fraction (MCF= stroke volume/myocardial volume) and MAPSE were worse in AS-CA. GLS, RELAPS, SAB and EFSR were not different, but RELAPS >1 pattern was more prevalent in AS-CA (74% vs 44%, p=0,006) (Figure 1). Mass/strain ratio (RMS) was similar. There were no differences in size and fractional emptying of left atrium, or atrial septum thickness. Right ventricle (RV) size was similar, as well as conventional function parameters (TAPSE and S'). However, RV LS was worse in AS-CA. Pericardial effusion was more prevalent in AS-CA (25% vs 7.4%, p=0.013). In the multivariate analysis, predictors of AS-CA were: Age (OR: 1,2, p=0,02), BG (OR: 0,2, p=0,01), E/A (OR: 4,7, p=0,02), LV Mass index (OR: 1,02, p=0,04) and RELAPS >1 (OR: 0,12, p=0,01). Conclusion(s): Dual pathology of AS-AC is common in older patients referred for TAVI. Although it is more prevalent in patients with AS-CA, RELAPS>1 pattern can be present in almost 50% of patients with severe AS alone, which reduces its value as screening tool for CA in this clinical setting respect to others. (Table Presented).

Cardiac findings in multisystem inflammatory syndrome in children (MIS-C) - single institution experience

Background: Multisystem inflammatory syndrome in children (MIS-C), associated with coronavirus disease 2019 (COVID-19) is a rare but serious condition, affecting children mostly after acute SARS CoV2 infection. MISC presents with fever, laboratory evidence of inflammation, and multiorgan dysfunction, including heart. Purpose(s): We analized the degree of cardiac involvement and clinical outcomes of MIS-C patients hospitalized in Pediatric department of Cantonal hospital Zenica, to compare with previously reported findings. Method(s): Cardiac testing results in pediatric patients hospitalized with MIS-C from November 2020. until March 2022. were retrospectively analized. For this study, MIS-C patients with positive cardiac testing were defined as having an abnormality of one or more of the following on admission: Cardiac biomarkers, electrocardiogram, and/or echocardiogram. Result(s): Cardiac abnormal findings were present in almost all of our ten patients with MIS-C, but the extent of cardial injury was lower than we expected it to be. Abnormal EKG was found in 80% patients with the most common electrocardiography findings: Low voltage (50%) and T wave abnormality (70%). Echocardiography abnormalities were present in 80% patients mostly including valvular regurgitation (mitral, pulmonal), and rarely pericardial effusion or left ventricular diastolic disfunction (20%). Elevated cardiac biomarkers were seen in 70% patients. By the time of hospital discharge or short time follow-up all cardiological findings were diminished. Six months follow-up found no cardiac sequellae and 24h electrocardiogram with heart rate variability parametres found no disturbancies outside physiological or underlying chronic disease. Conclusion(s): While most patients in our study had evidence of abnormal cardiac testing on hospital admission, all cardiac findings were normal by hospital discharge. Cardiologic findings were representative for subacute myocardial injury with good clinical outcome and no sequellae. The degree of cardiac involvement was mild compared with previous reports.

Cardiopulmonary long-term effects in patients after hospitalization due to COVID-19 infection

Background: Multiple studies have described acute effects of the Covid-19 infection on the heart, but little is known about the long-term cardiac and pulmonary effects and complications after recovery. The aim of this analysis was to deliver a comprehensive report of symptoms and possible long-term impairments after hospitalization because of Covid-19 infection as well as to try to identify predictors for Long-Covid. Method(s): This was a prospective, multicenter registry study. Patients with verified Covid-19 infection, who were treated as in-patients at our dedicated Covid hospital (Clinic Favoriten), have been included in this study. In all patients, testing was performed approximately 6 months post discharge. During the study visit the following tests and investigations were performed: Detailed patient history and clinical examination, transthoracic echocardiography, electrocardiography, cardiac magnetic resonance imaging (MRI), chest computed tomography (CT) scan, lung function test and a comprehensive list of laboratory parameters including cardiac bio markers. Result(s): Between July 2020 and October 2021, 150 patients were recruited. Sixty patients (40%) were female and the average age was 53.5+/-14.5 years. Of all patients, 92% had been admitted to our general ward and 8% had a severe course of disease, requiring admission to our intensive care unit. Six months after discharge the majority of patients still experienced symptoms and 75% fulfilled the criteria for Long-Covid. Only 24% were completely asymptomatic (figure 1). Echocardiography detected reduced global longitudinal strain (GLS) in 11%. Cardiac MRI revealed pericardial effusion in 18%. Furthermore, cardiac MRI showed signs of former peri-or myocarditis in 4%. Pulmonary CT scans identified post-infectious residues, such as bilateral ground glass opacities and fibrosis in 22%. Exertional dyspnea was associated with either reduced forced vital capacity measured during pulmonary function tests in 11%, with reduced GLS and/or diastolic dysfunction, thus providing evidence for a cardiac and/or pulmonary cause. Independent predictors for Long-Covid were markers of a more severe disease course like length of in-hospital stay, admission to an intensive care unit, type of ventilation as well as higher NT-proBNP and/or troponin levels. Conclusion(s): Even 6 months after recovery from Covid-19 infection, the majority of previously hospitalized patients still suffer from at least one symptom, such as chronic fatigue and/or exertional dyspnea. While there was no association between fatigue and cardiopulmonary abnormalities, impaired lung function, reduced GLS and/or diastolic dysfunction were significantly more prevalent in patients presenting with exertional dyspnea. On chest CT approximately one fifth of all patients showed post infectious changes in chest CT including evidence for myo-and pericarditis as well as accumulation of pericardial effusions.

Subclinical myocardial dysfunction in patients with persistent dyspnea one year after COVID-19

Introduction: Coronavirus disease 2019 (COVID-19) rapidly spread across the globe,evolving into a global pandemic,with a crucial impact on healthcare systems. Several short-term follow-up studies emphasized the persistence of symptoms, referred as long COVID, in a significant number of discharged patients even without history of cardiopulmonary diseases, with dyspnea being one of the most frequent complaint [1-3]. Even though those reports on recovered COVID-19 patients did not describe major left ventricle (LV) function abnormalities, subtle cardiac changes may be present. Purpose(s): We aimed to investigate the presence of subclinical cardiac dysfunction, assessed by transthoracic echocardiography (TTE) in recovered COVID-19 patients, without previous cardiopulmonary disease at 1 year follow-up. Method(s): 310 COVID-19 consecutive hospitalized patients were prospectively included between March and April 2020. 66 patients out of 251 recovered patients had no previous history of coronary artery disease, arrhythmia, arterial hypertension, valvular heart disease, asthma, chronic obstructive pulmonary disease and obstructive sleep apnea, respectively and were included in the final analysis (Figure 1). The follow-up consisted in 2 parts, a 6-months visit including clinical and physical examination, chest computed tomography and spirometry and a 12-months visit including clinical and physical examination, spirometry and TTE. Result(s): 66 patients (mean age 51.39+/-11.15 years, 45 (68.2%) males) were included in the final analysis. 23 (34.8%) patients reported dyspnea at 1 year. TTE parameters were in the normal range, with a mean LV ejection fraction of 56.9+/-4.6%, mean global longitudinal strain (GLS) of -20.9+/-2.3%, global constructive work (GCW) of 2381.4+/-463.6 mmHg% and global work index (GWI) of 2132.5+/-419.2 mmHg%. Type 1 diastolic dysfunction was observed in 11 (16.7%) patients. One (1.5%) patient had type 2 diastolic dysfunction. A normal respiratory pattern was reported in 31 (47%) patients at 6 months spirometry, while 19 (28.8%) patients had a restriction pattern. No significant differences regarding clinical, laboratory or imaging findings at baseline were found between groups. The following TTE parameters were significantly different in patients with and without dyspnea at 1 year: GLS (-19.97+/-2.14 vs. -21.38+/-2.37, p=0.039), GCW (2183.72+/-487.93 vs. 2483.14+/-422.42, p=0.024) and GWI (1960.06+/-396.21 vs. 2221.17+/-407.99, p=0.030). Multivariable logistic regression showed that GCW and GWI were inversely and independently associated with persistent dyspnea, one year after COVID-19 (p=0.035, OR 0.998, 95% CI 0.997-1.000;p=0.040, OR 0.998, 95% CI 0.997-1.000) (Table 1). Conclusion(s): Persistent dyspnea one year after COVID-19 was present in more than a third of patients without known cardiovascular or pulmonary diseases. GCW and GWI were the only echocardiographic parameters independently associated with symptoms, suggesting a decrease in myocardial performance in this population and subclinical cardiac dysfunction.

Right ventricular myocardial dysfunction in patients (pts) after severe coronavirus disease (COVID-19)

Aim: To study the systolic function (SF) and diastolic function (DF) of the heart and to assess subclinical myocardial right ventricular (RV) dysfunction in pts after severe COVID-19. We examined 23 males aged 46-70 years (mean age - 58.8 +/- 12.6 yrs) discharged after COVID-19 (50-75% of the parenchymal damage) with exertional dyspnea. We performed transthoracic echocardiography (TTE) with assessment of RV global longitudinal strain (RV-GLS) and right ventricular free wall longitudinal strain (RVLS) using speckle tracking echocardiography. Result(s): The SF of the RV assessed by the excursion of the tricuspid valve ring (TAPSE) was preserved (2.1 +/- 0.6 cm) in all pts under study after severe COVID-19. The left ventricular (LV) ejection fraction was also preserved (62.1 +/- 4.7%) in all pts. TTE revealed normal ventricular and atrial dimensions: LV end-diastolic volume index (62.5 +/- 8.4 ml/m2) and RV end-diastolic diameter (2.7 +/- 0.6 cm), left atrial (LA) volume index (26.7 +/- 3.1 ml/m2) and right atrial (RA) volume index (20.2 +/- 4.5 ml/m2). LV DD was also detected: Grade I in 17 (74%) pts, and Grade II in 6 (16%) pts. Moderate pulmonary hypertension (PH) was present in all pts (time of acceleration of systolic flow in the pulmonary artery (AcT - 85.0 +/- 7.9 msec) as a consequence of significant pulmonary parenchymal involvement. We found reduced RV-GLS (-17.4 +/- 2.7%) and free wall RVLS (-18.9 +/- 3.1%) in 23 (100%) pts. Conclusion(s): Preserved LV and RV SF with Grade 1 and Grade 2 LV DD and moderate PH were established in pts after severe COVID-19. RV wall motion abnormalities with reduced RV-GLS and free wall RVLS were found, indicating the presence of subclinical RV myocardial dysfunction.

Connections between Diabetes Mellitus and Metabolic Syndrome and the Outcome of Cardiac Dysfunctions Diagnosed during the Recovery from COVID-19 in Patients without a Previous History of Cardiovascular Diseases.

(1) Background: Throughout the COVID-19 pandemic, it became obvious that individuals suffering with obesity, diabetes mellitus (T2DM), and metabolic syndrome (MS) frequently developed persisting cardiovascular complications, which were partially able to explain the onset of the long-COVID-19 syndrome. (2) Methods: Our aim was to document, by transthoracic echocardiography (TTE), the presence of cardiac alterations in 112 patients suffering from post-acute COVID-19 syndrome and T2DM, MS, and/or obesity, in comparison to 91 individuals without metabolic dysfunctions (MD); (3) Results: in patients with MD, TTE borderline/abnormal left (LVF) and/or right ventricular function (RVF), alongside diastolic dysfunction (DD), were more frequently evidenced, when compared to controls (p ˂ 0.001). Statistically significant associations between TTE parameters and the number of factors defining MS, the triglyceride-glucose (TyG) index, the severity of the SARS-CoV-2 infection, and the number of persisting symptoms (p ˂ 0.001) were noted. Significant predictive values for the initial C-reactive protein and TyG index levels, both for the initial and the 6-month follow-up levels of these TTE abnormalities (p ˂ 0.001), were highlighted by means of a multivariate regression analysis. (4) Conclusions: in diabetic patients with MS and/or obesity with comorbid post-acute COVID-19 syndrome, a comprehensive TTE delineates various cardiovascular alterations, when compared with controls. After 6 months, LVF and RVF appeared to normalize, however, the DD-although somewhat improved-did persist in approximately a quarter of patients with MD, possibly due to chronic myocardial changes.

Left atrial longitudinal strain analysis in long Covid-19 syndrome.

It is known that during the active course of Coronavirus disease 2019 (COVID-19), myocardial injury has an established pathological base, while its myocardial injury post-recovery is still obscured.The aim of this study was to evaluate the longitudinal left atrial strain (LAS) using speckle tracking echocardiography (STE) in COVID-19-recovered patients who are previously healthy without confounder comorbidities to detect the potential cardiac dysfunction.200 patients were prospectively included and examined 4?12 weeks after recovery from COVID-19 infection. 137 participants with comorbidities or previous history of cardiopulmonary disease were excluded from the analysis. A total of 63 patients who fulfilled our inclusion criteria were recruited into two groups according to thepresence or absence of persistent dyspnoea and exercise intolerance. Clinical, laboratory & comprehensive echocardiographic examinations were done for all. We observed that 31.7% of the previously healthy individuals developed dyspnoea & exercise intolerance post-COVID-19 infection. There were significantly impaired LAS parameters in the symptomatic group (LA reservoir, contraction & conduit strain, 22.7%, -6.6% & -16.1% versus 40%, -12%, and ? 27% in the asymptomatic group with P < 0.000). Only LA reservoir strain and LA stiffness can independently predict the development of dyspnoea & exercise intolerance post-COVID-19 at cut-off values of 30% & 24.5% respectively with a sensitivity of 90% and a specificity of 91%, P < 0.001. These impaired LAS parameters could explain the developed symptoms post-COVID-19 recovery, even before disturbed conventional diastolic echocardiographic parameters.LAS parameters are significantly associated with the developed exertional dyspnoea & exercise intolerance post-COVID-19. LA reservoir strain & LA stiffness could provide a simple, easily available tool that points to early LV diastolic dysfunction and may direct the therapy in this subset of the population.

Correspondence between Aortic and Arterial Stiffness, and Diastolic Dysfunction in Apparently Healthy Female Patients with Post-Acute COVID-19 Syndrome.

(1) Background: Abnormally increased arterial and aortic stiffness (AS and AoS), which are often associated with diastolic dysfunction (DD), represent common alterations in COVID-19. In this study, we aimed to assess, by transthoracic echocardiography (TTE) and pulse-wave velocity (PWV), the frequency of these dysfunctions in patients with post-acute COVID-19 syndrome and to highlight potential correlations between their severity and multiple clinical and laboratory parameters. (2) Methods: In total, 121 women were included in our study, all of whom were younger than 55 and had been diagnosed with post-COVID-19 syndrome. Of those women, 67 also had metabolic syndrome (MS) (group A), whereas the other 54 did not (group B); 40 age-matched healthy subjects were used as controls (group C). (3) Results: Patients in group A had worse values of indexes characterizing AS and AoS and had more frequent DD compared to those from group B and group C (p < 0.0001). The statistical analysis evidenced significant associations between these indexes and the time that had elapsed since COVID-19 diagnosis, the factors that characterize the severity of the acute disease and those that specify MS. Multivariate regression analysis identified the following as the main independent predictors for DD: values of the AoS index, the C-reactive protein, and the triglyceride-glucose index. (4) Conclusions: Altered AS, AoS, and DD are common in patients with post-COVID-19 syndrome, especially with concurrent MS, and these parameters are apparently associated not only with the severity and time elapsed since COVID-19 diagnosis but also with MS.

Characteristic Immune Dynamics in COVID-19 Patients with Cardiac Dysfunction.

BACKGROUND: We aimed to explore immune parameters in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. METHODS: A total of 30 COVID-19 patients >18 years admitted to the ICU were studied on days D1, D3 and D7 after admission. Cardiac function was assessed using speckle-tracking echocardiography (STE). Peripheral blood immunophenotyping, cardiac (pro-BNP; troponin) and inflammatory biomarkers were simultaneously evaluated. RESULTS: Cardiac dysfunction (DYS) was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. High-sensitivity cardiac troponin (hs-cTn) was detectable in 43.3% of the patients with a median value of 13.00 ng/L. There were no significant differences between DYS and nDYS patients regarding mortality, organ dysfunction, cardiac (including hs-cTn) or inflammatory biomarkers. Patients with DYS showed persistently lower lymphocyte counts (median 896 [661-1837] cells/µL vs. 2141 [924-3306] cells/µL, p = 0.058), activated CD3 (median 85 [66-170] cells/µL vs. 186 [142-259] cells/µL, p = 0.047) and CD4 T cells (median 33 [28-40] cells/µL vs. 63 [48-79] cells/µL, p = 0.005), and higher effector memory T cells (TEM) at baseline (CD4%: 10.9 [6.4-19.2] vs. 5.9 [4.2-12.8], p = 0.025; CD8%: 15.7 [7.9-22.8] vs. 8.1 [7.7-13.7], p = 0.035; CD8 counts: 40 cells/µL [17-61] vs. 10 cells/µL [7-17], p = 0.011) than patients without cardiac dysfunction. CONCLUSION: Our study suggests an association between the immunological trait and cardiac dysfunction in severe COVID-19 patients.

Copeptin and Cardiovascular Function Correlation in Children with Multisystem Inflammation Syndrome

INTRODUCTION: Children exposed to COVID-19 can develop Multisystem Inflammation Syndrome in Children (MIS-C). Literature has shown that 80% of affected children have cardiovascular involvement. Copeptin, a provasopressin protein, has been shown to correlate with myocardial injury and failure. Copeptin is a stable biomarker with minimal variation in a healthy population. We hypothesize that copeptin levels will correlate with troponin and Brain Natriuretic Peptide (BNP) levels and echocardiogram findings of left ventricular dysfunction in MIS-C. METHOD(S): We conducted a prospective study with subjects admitted to the Pediatric Intensive Care Unit who met WHO criteria for MIS-C between 2021-2022. Within 24 hours of initiating therapy, consent and a whole blood sample was obtained. The plasma was evaluated by enzyme-linked immunosorbent assay for a copeptin level. Troponin and BNP were drawn as standard of care. Echocardiograms obtained within 24 hours of the copeptin sample were evaluated for dysfunction. Comparisons between copeptin and troponin, BNP, and Ejection Fraction (EF) were evaluated using Wilcoxon Signed Rank Test. Comparisons of copeptin across echocardiogram markers of diastolic dysfunction (EE' ratio, EA ratio) and diastolic dimensions (LV diastolic dimeter index (LVDd), septal diastolic diameter index (LVSDd), and posterior wall diastolic diameter index (LVPWDd)) were evaluated using Friedman's Test. Kruskal-Wallis test was used to compare copeptin levels in patients on vasopressor support. RESULT(S): Ten patients with a clinical diagnosis of MIS-C were recruited. While copeptin levels (normal range 4-45pg/ ml, subjects range 19.5-963pg/ml) were not significantly different between patients who received vasopressors (p=0.088), LVSDd (p=< 0.001) and LVPWDd (< 0.001) did differ. Significant differences were found between copeptin and EA ratio (p=0.006) but not with EE' ratio (p=0.495). Differences between copeptin and EF were statistically significant (p=0.007). Comparisons of copeptin with troponin (p=0.007) and BNP (p=0.005) were also significant. CONCLUSION(S): Copeptin is a biomarker that has the potential to indicate cardiac dysfunction in the MIS-C population. Elevated copeptin levels correlated with echocardiogram findings of systolic dysfunction and diastolic dysfunction in children with MIS-C.

Left Ventricular Diastolic Dysfunction Screening by a Smartphone-Case Based on Single Lead ECG.

Aims: To investigate the potential of a signal processed by smartphone-case based on single lead electrocardiogram (ECG) for left ventricular diastolic dysfunction (LVDD) determination as a screening method. Methods and Results: We included 446 subjects for sample learning and 259 patients for sample test aged 39 to 74 years for testing with 2D-echocardiography, tissue Doppler imaging and ECG using a smartphone-case based single lead ECG monitor for the assessment of LVDD. Spectral analysis of ECG signals (spECG) has been used in combination with advanced signal processing and artificial intelligence methods. Wavelengths slope, time intervals between waves, amplitudes at different points of the ECG complexes, energy of the ECG signal and asymmetry indices were analyzed. The QTc interval indicated significant diastolic dysfunction with a sensitivity of 78% and a specificity of 65%, a Tpeak parameter >590 ms with 63% and 58%, a T value off >695 ms with 63% and 74%, and QRSfi > 674 ms with 74% and 57%, respectively. A combination of the threshold values from all 4 parameters increased sensitivity to 86% and specificity to 70%, respectively (OR 11.7 [2.7-50.9], P < .001). Algorithm approbation have shown: Sensitivity-95.6%, Specificity-97.7%, Diagnostic accuracy-96.5% and Repeatability-98.8%. Conclusion: Our results indicate a great potential of a smartphone-case based on single lead ECG as novel screening tool for LVDD if spECG is used in combination with advanced signal processing and machine learning technologies.

Challenges for Management of Dilated Cardiomyopathy during COVID-19 Pandemic-A Telemedicine Application.

BACKGROUND AND OBJECTIVES: The 2019 coronavirus pandemic (COVID-19) represented a significant challenge for the medical community. The first aim of this study was to examine the COVID-19 impact on the follow-up of patients with dilated cardiomyopathy (DCM) and to establish the advantages of multiparametric home monitoring. Also, we tried to establish the main prognostic predictors at 2-years follow-up and the value of LV diastolic filling pattern (LVDFP) in increasing mortality and morbidity. MATERIALS AND METHODS: We conducted a prospective study of 142 patients with DCM assessed by in-patient visit in the pre-pandemic period and hybrid (face-to-face, online consultation and telemedicine home monitoring with a dedicated application) during the pandemic period. The statistical analysis compared the strategy used in the pre-pandemic with management during the pandemic, in terms of clinical assessment, hospitalizations/emergency room visits due to HF exacerbation and total mortality. RESULTS: We did not observe significant changes in blood pressure (BP), heart rate (FC), weight and symptoms or an increased rate of adverse drug events between the two periods. We successfully titrated HF medications with close monitoring of HF decompensations, which were similar in number, but were mostly managed at home during the pandemic. There was also no statistically significant difference in emergency room visits due to severe decompensated HF. Mortality in the first and second year of follow-up was between 12.0 and 13%, similar in the pre-pandemic and pandemic periods, but significantly higher in patients with restrictive LVDFP. Clinical improvement or stability after 2 years was more frequent in patients with nonrestrictive LVDFP. The main prognostic predictors at 1 and 2-years follow-up were: the restrictive LVDFP, significantly dilated LV, comorbidities (DM, COPD), older age, associated severe mitral regurgitation and pulmonary hypertension. CONCLUSIONS: The pandemic restrictions determined a marked decrease of the healthcare use, but no significant change in the clinical status of DCM patients under multiparametric home monitoring. At 2-years follow-up, the presence of the restrictive LVDFP was associated with an increased risk of death and with a worse clinical status in DCM patients.

A Rare Case of Magic Mushroom (Psilocybin) Related AKI and Hypertensive Emergency

Introduction: Magic (Psilocybin) mushrooms are used as hallucinogens, renal dysfunction as a rare side effect has been reported in literature. We chronicle a rare case of acute kidney injury and hypertensive emergency precipitated by psilocybin ingestion in a young female. Case Description: A 31-year-old female with good overall health and medical history of well controlled Hypertension (HTN) and metabolic syndrome presented with AKI in the setting of hypertensive emergency. Initial blood pressure (BP) on presentation was 210/140, with transient visual loss and elevated troponin >6000. Her other past medical history was significant for nephrolithiasis and COVID-19 few months ago. Physical examination was significant for HTN;no significant edema was present. Remaining physical examination was unremarkable. Laboratory evaluation demonstrated serum creatinine 4.6 mg/dL (baseline creatinine 0.9 mg/dL), 24-hr urine protein 920 mg/g, and serum albumin 3.0 g/dl. A blood film revealed occasional schistocytes. Urinalysis showed proteinuria and microscopic hematuria. Urine toxicology screen was negative. Routine blood and urine cultures showed no growth. Her serology, infectious disease workup and workup for paraproteinemia were inconclusive. Workup for secondary hypertension was negative. Computed tomography of the brain in the setting of transient visual loss, and ultrasound of the kidneys and bladder were unremarkable. Her transthoracic echo (TTE) showed severe concentric left ventricular hypertrophy, with grade II diastolic dysfunction. Renal biopsy showed features suggestive of vascular-predominant acute thrombotic microangiopathy. Patient was managed conservatively and did not require renal replacement therapy. Her serial follow up labs from last several months revealed the new baseline creatinine of 2.2-2.4 mg/dl, resulting in CKD as a sequel of partial recovery from AKI in the setting of psilocybin poisoning. Discussion(s): Psilocybin use can be associated with AKI leading to CKD and secondary hypertension. Mechanisms of renal injury are thought to be secondary to vasoconstricting effects and endothelial reaction, which needs to be further investigated. Nephrologists and primary providers should be vigilant to identify this rare cause of AKI.

SARS-CoV-2 infection causes prolonged cardiomyocyte swelling and inhibition of HIF1α translocation in an animal model COVID-19.

Recovered COVID-19 patients often display cardiac dysfunction, even after a mild infection. Most current histological results come from patients that are hospitalized and therefore represent more severe outcomes than most COVID-19 patients face. To overcome this limitation, we investigated the cardiac effects of SARS-CoV-2 infection in a hamster model. SARS-CoV-2 infected hamsters developed diastolic dysfunction after recovering from COVID-19. Histologically, increased cardiomyocyte size was present at the peak of viral load and remained at all time points investigated. As this increase is too rapid for hypertrophic remodeling, we found instead that the heart was oedemic. Moreover, cardiomyocyte swelling is associated with the presence of ischemia. Fibrin-rich microthrombi and pericyte loss were observed at the peak of viral load, resulting in increased HIF1α in cardiomyocytes. Surprisingly, SARS-CoV-2 infection inhibited the translocation of HIF1α to the nucleus both in hamster hearts, in cultured cardiomyocytes, as well as in an epithelial cell line. We propose that the observed diastolic dysfunction is the consequence of cardiac oedema, downstream of microvascular cardiac ischemia. Additionally, our data suggest that inhibition of HIF1α translocation could contribute to an exaggerated response upon SARS-CoV-2 infection.

SARS-CoV-2 infection causes cardiomyocyte swelling, cardiac pericyte loss, increased permeability, and diastolic dysfunction in a hamster model

Background/Introduction: Recovered COVID-19 patients often display cardiac dysfunction, even after a relatively mild infection. Purpose: We present an in-depth physiological and histological timeline of the cardiac consequences of SARS-CoV-2 infection using a hamster model. Methods: We used several methods, including transthoracic echocardiography, RNA sequencing on in vitro cultures, and in-situ hybridization techniques, complemented with histological analysis. Results: We analysed cardiac function by echocardiography over a period of 35 dpi. Already by 14 dpi and continuing at 35 dpi, infected hamsters presented with an increased E/E', decreased MV deceleration time, and an increased isovolumetric contraction time as compared to control, indicating the presence of diastolic dysfunction. Histologically, cardiomyocytes were enlarged already by 4 dpi and remained enlarged over 5 weeks. We observed the presence of fibrin-rich microthrombi at 4 dpi, which were resolved by 14 dpi. SARS-CoV-2 RNA was present in cardiac pericytes, accompanied by reduced pericyte coverage of capillaries at 4 dpi and 14 dpi, which mostly recovered by 35 dpi. At 14 dpi, the reduced pericyte coverage coincided with increased vascular permeability, suggesting that SARS-CoV-2 infection of pericytes affects microvascular integrity. SARS-CoV-2 infection of pericytes in vitro induced the expression of genes involved in viral defence, and affected genes involved in pericyte contractility and extracellular matrix proteins. Loss of cardiac pericytes was observed in cardiac biopsies from patients recovered from SARSCoV- 2 infection. Conclusion(s): Overall, our results demonstrate that SARS-CoV-2 infection causes a phenotype similar to ischemia-reperfusion, without overt ischemia. We propose that partial occlusion by microthrombi and microvascular dilation caused by pericyte loss induces regional variations in blood flow, and results in a stiffer ;swollen' heart that shows diastolic dysfunction.

Cardiac manifestations of multisystem inflammatory syndrome in children

Background and Aim: We aimed to evaluate cardiac manifestations of the multisystem inflammatory syndrome in children(MIS-C) and the changes in cardiac function during one year of follow-up. Method(s): All children diagnosed as MIS-C with cardiac involve-ment were enrolled in this prospective study. The diagnosis and severity of the disease of MIS-C was made according to the Centers for Disease Control and World Health Organization guidelines. Clinical findings, laboratory parameters including car-diac markers, electrocardiographic and echocardiographic findings at the time of diagnosis and during follow-up were evaluated. Cardiac magnetic resonance imaging (MRI) was performed on all children with echocardiographic abnormality. Result(s): Between April 1st 2020 and December 1st 2021,71 chil-dren were diagnosed with MIS-C and 44 of these patients had car-diac involvement (25 male and 19 female). 24 patients were followed up in the intensive care unit and all of these patients had myocardial involvement. All the patients had elevated NT-proBNP levels (median:5893pg/ml) whereas troponin-T levels were above upper limit in 13 patients. A significant positive cor-relation was found between troponin-T and NT-proBNP (plt;0.01). The NT-proBNP levels were also positively correlated with the severity of MIS-C (plt;0.05). On admission 22 patients had tachycardia and atrioventricular conduction disturbances and supraventricular tachycardia developed in 5 of these patients during follow-up. Bradycardia was observed in 18(40%) patients during hospitalization (4 of these occurred after tachycardia). Although 26 patients had an echocardiographic abnormality, only twelve patients had systolic dysfunction (9 with mild and 3 with moderate) and two patients had diastolic dysfunction. NT-proBNP and troponin-T were negatively correlated with ejection fraction ve fractional shortening (respectively, p = 0.003, p = 0.013). Cardiac MRI was normal in all patients except 3 patients who had myocardial late gadolinium enhancement of left ven-tricle. Pericardial effusion was observed in 14 patients. The echo-cardiographic abnormalities disappeared in 42 patients during follow-up, one patient died on the second day of hospitalization and and 1 patient has ongoing LV systolic dysfunction. Conclusion(s): Bradycardia and myocardial involvement is common during MIS-C. Although myocardial dysfunction can be observed during acute disease, commonly the disease does not cause perma-nent damage during one year of follow-up.

Echocardiographic Evaluation of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19

Cardiac involvement is an observable issue in multisystem inflammatory syndrome in children (MIS-C) associ20 ated with COVID-19. The most common echocardiographic findings in MIS-C are abnormal coronary arteries, decreased left ventricular function, mitral regurgitation, and pericardial effusion. Abnormalities in the coronary arteries were seen in less than 20% of MIS-C patients. These abnormalities include dilatation or aneurysms in the coronary arteries;however, giant or large aneurysms are rare. On the other hand, transient coronary artery dilatation (which can occur secondary to viral myocarditis) may also mean that the coronary artery Z-scores never exceed 2.5. Reviewing large case series revealed that approximately 30 - 40% of MIS-C patients had decreased left ventricular function. In most cases, left ventricular function is mildly depressed, and severe left ventricular dysfunction was observed in only one-fifth of cases. Hypoxia, myocardial ischemia secondary to coronary involvement, stress-induced cardiomyopathy, injury caused by systemic inflammation, and viral myocarditis are the possible etiologies for the myocardial injury in MIS-C. It is now clear that myocardial strain imaging indices such as a global longitudinal strain (GLS), end-diastolic strain rate (EDSR), and peak left atrial strain (LAS) can demonstrate systolic or diastolic dysfunction in myocarditis patients with preserved left ventricular ejection fraction. Furthermore, right-sided ventricular deformation imaging abnormalities have been reported in adult patients with MIS-C. Less information is currently available on mitral regurgitation and pericardial effusion in pediatric patients with MIS-C;however, in an extensive study on 286 pediatric patients with MIS-C, 28% had pericardial effusion, and 42.7% had mitral regurgitation;both were mild in most patients.