Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation.

BACKGROUND: Subclinical myocardial dysfunction may exist in post-COVID-19 patients and may carry significance in long term. METHODOLOGY: Subjects of long-COVID-19 with historically and radiologically significant pulmonary involvement (without documented cardiac involvement) were evaluated on outpatient follow-up echocardiographically when they had disproportionate shortness of breath (SOB), fatigue, or high pulse rate as perceived by the physicians. The common acute-phase symptoms were noted and scored retrospectively. The assessment included spirometry and measurement of chronic obstructive pulmonary disease (COPD) assessment test (CAT) score with measurement of the left ventricular (LV) and right ventricular (RV) free wall global longitudinal strain as an adjunct to routine two-dimensional and Doppler echocardiography and spirometry. The results were evaluated statistically with respect to the history of hospitalization. RESULTS: The hospitalized (n = 15) and nonhospitalized (n = 10) patients were demographically similar. However, the nonhospitalized patients had higher total symptom score (p = 0.03), anosmia (p = 0.017), and ageusia (p = 0.0019). At follow-up (>3 months of acute illness), the nonhospitalized patients had a better CAT score (p = 0.04), higher change in max pulse rate (p = 0.03), and higher forced expiratory volume in 1 second (FEV1) (p = 0.002), tricuspid annular plane systolic excursion (TAPSE) (p = 0.02), and left ventricular global longitudinal strain (LVGLS) (-17.15 ± 1.19 vs -13.11 ± 1.91) (p = 0.0001). Overall, the two groups formed distinct clusters. The LVGLS and the maximum pulse rate difference in the two chair test (2CT) seem to contribute maximally to the variance between the two groups in multivariate analysis. CONCLUSION: The subclinical myocardial dysfunction persisting in post-COVID patients (without suspected cardiac affection and lower neuroinflammatory symptoms in the acute phase) with significant pulmonary affection needs further evaluation. They demonstrate a higher max pulse rate difference in the 2CT. This real-world observation demands further investigations.

Clinical profile and the extent of residual myocardial dysfunction among patients with previous coronavirus disease 2019.

BACKGROUND: Many patients who have recovered from their coronavirus disease 2019 (COVID-19) episode continue to remain symptomatic and seek medical opinion. The clinical characteristics and echocardiography findings of such subjects have not been adequately studied. METHODS: The study included 472 subjects (age 54.0 ± 13.4 years, 57% men) with previous COVID-19 (median duration since COVID-19 12.0 weeks, interquartile range 9.0-26.0 weeks) and 100 controls (age 53.9 ± 13.6 years, 53% men). All subjects underwent detailed clinical assessment and echocardiography, including measurement of left ventricular (LV) ejection fraction (EF) and global longitudinal strain (GLS). RESULTS: Less than third (29.2%) of the post-COVID subjects had needed hospitalization for their initial infection. Exertional dyspnea or breathing difficulty at rest were the commonest reasons for post-COVID presentation. As compared to controls, the post-COVID subjects had impaired LV systolic (LVEF 63.2 ± 2.2 vs. 61.9 ± 4.6, P = 0.007; GLS - 19.9 ± 2.6% vs. -17.6 ± 3.4%, P < 0.001) and diastolic function. Majority of those with reduced LV GLS had preserved LVEF. The patients presenting before 12 weeks were more likely to be symptomatic, but LV GLS did not differ. The patients needing hospitalization had higher burden of co-morbidities and significantly reduced LV GLS as compared to those who had received domiciliary treatment. The patients in the lowest GLS tertile were older, had higher burden of co-morbidities, and had had more severe initial infection with greater need for hospitalization, oxygen therapy and steroids. The need for hospitalization was independently associated with lower GLS at the time of current presentation. CONCLUSION: This study shows that impairment of LV systolic and diastolic function is common among subjects recovering from previous COVID-19 episode. The patients with more severe initial infection have more marked impairment of LV function and this impairment persists even after several months of recovery from the initial infection. Routine measurement of GLS may be helpful since LV systolic dysfunction in these patients is mostly subclinical.

Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation.

BACKGROUND: Subclinical myocardial dysfunction may exist in post-COVID-19 patients and may carry significance in long term. METHODOLOGY: Subjects of long-COVID-19 with historically and radiologically significant pulmonary involvement (without documented cardiac involvement) were evaluated on outpatient follow-up echocardiographically when they had disproportionate shortness of breath (SOB), fatigue, or high pulse rate as perceived by the physicians. The common acute-phase symptoms were noted and scored retrospectively. The assessment included spirometry and measurement of chronic obstructive pulmonary disease (COPD) assessment test (CAT) score with measurement of the left ventricular (LV) and right ventricular (RV) free wall global longitudinal strain as an adjunct to routine two-dimensional and Doppler echocardiography and spirometry. The results were evaluated statistically with respect to the history of hospitalization. RESULTS: The hospitalized (n = 15) and nonhospitalized (n = 10) patients were demographically similar. However, the nonhospitalized patients had higher total symptom score (p = 0.03), anosmia (p = 0.017), and ageusia (p = 0.0019). At follow-up (>3 months of acute illness), the nonhospitalized patients had a better CAT score (p = 0.04), higher change in max pulse rate (p = 0.03), and higher forced expiratory volume in 1 second (FEV1) (p = 0.002), tricuspid annular plane systolic excursion (TAPSE) (p = 0.02), and left ventricular global longitudinal strain (LVGLS) (-17.15 ± 1.19 vs -13.11 ± 1.91) (p = 0.0001). Overall, the two groups formed distinct clusters. The LVGLS and the maximum pulse rate difference in the two chair test (2CT) seem to contribute maximally to the variance between the two groups in multivariate analysis. CONCLUSION: The subclinical myocardial dysfunction persisting in post-COVID patients (without suspected cardiac affection and lower neuroinflammatory symptoms in the acute phase) with significant pulmonary affection needs further evaluation. They demonstrate a higher max pulse rate difference in the 2CT. This real-world observation demands further investigations.

Cardiovascular Magnetic Resonance in Children with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: Institutional Protocol-Based Medium-Term Follow-up Study.

Multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19 infection in previously healthy children often results in subtle but persistent echocardiographic abnormalities despite complete clinical recovery. This study was done to investigate medium-term cardiovascular outcomes of patients with MIS-C using cardiovascular magnetic resonance imaging (CMR). This is a single-center retrospective study of patients aged less than 21 years, diagnosed with MIS-C who received an outpatient CMR, around 6 months after discharge. CMR was done in patients with significant troponin leak or depressed LVEF. CMR performed on a GE Signa HDxt 1.5 Tesla magnet with a myocarditis protocol. Diagnosis of myocarditis was determined by the original Lake Louise Criteria. There were 21 patients with a median age of 11 years, (IQR 8-13 years), who underwent CMR at median follow-up duration of 6 months (IQR 5-7 months). At the peak of illness during admission, there were 95.2% patients with abnormal Troponin I and BNP. By echocardiogram, 76.2% had left ventricular systolic dysfunction and 9.5% had coronary ectasia, which all resolved by 6 months. By CMR, there were five patients (23.8%) with abnormal left atrial volume, one patient (4.8%) with an abnormal indexed left ventricular end-diastolic volume, and three patients (15%) with abnormal LVEF. There was no evidence of myocardial edema in T2-weighted image sequence. There were three patients with persistent late gadolinium enhancement (14.3%). Follow-up CMR is a useful tool in diagnosing subtle myocardial abnormalities and guide necessity for future follow-up.

Incidence, risk factors and prognostic effect of imaging left ventricular diastolic dysfunction in patients with COVID-19: protocol for a systematic review.

INTRODUCTION: Recent reports linked acute COVID-19 infection in critical patients to cardiac structure and function abnormalities. The left ventricular (LV) diastolic dysfunction could result in obvious adverse prognostic impacts. The aim of this meta-analysis is to summarise the incidence, risk factors and the prognostic effect of imaging LV diastolic dysfunction in adult patients with COVID-19. METHODS: Databases to be used for the pertinent literature are PubMed, EMBase, ISI Knowledge via Web of Science, and preprint databases (MedRxiv and BioRxiv) (until May 2023) to identify all cohort studies in adult patients with COVID-19. The primary outcome will be the incidence of LV diastolic dysfunction assessed by echocardiography or cardiac MRI. Secondary outcomes will include the risk factors for LV diastolic dysfunction and the association with all-cause mortality during hospitalisation. Additional outcomes will be septal or lateral é, average E/é, E/A, peak tricuspid regurgitation velocity, left atrial volume index and LV wall thickness. Univariable or multivariable meta-regression and subgroup analyses will be conducted for related risk factors and the association of LV diastolic dysfunction with all-cause mortality. Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of LV diastolic dysfunction incidence and related risk factors, association with all-cause mortality and other LV diastolic dysfunction parameters. ETHICS AND DISSEMINATION: There was no need for ethics approval for the systematic review protocol according to the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital. This meta-analysis will be disseminated through a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42021256666; URL: https://www.crd.york.ac.uk/prospero/.

Is strain echocardiography a more sensitive indicator of myocardial involvement in patients with multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2?

OBJECTIVE: The aim of the study was to evaluate the early myocardial dysfunction detected by strain echocardiography in children with multisystem inflammatory syndrome related to SARS-CoV-2 infection. METHODS: This cross-sectional study was conducted with 47 patients diagnosed with MIS-C and 32 healthy age- and gender-matched children. All patients underwent two-dimensional, colour, pulsed, and tissue Doppler, and 2D speckle tracking echocardiography examination at admission, 2 weeks, and 2 months after discharge. The MIS-C patient group was compared with the control group. Echocardiographic changes in MIS-C patients during follow-up were evaluated. RESULTS: Of 47 patients, 30 (63.8%) were male and 17 (36.2%) were female. The mean age at diagnosis was 9.1 ± 4.3 (1.25-17) years. At admission, 25 patients had abnormal findings on conventional echocardiography. Among them, eight patients had left ventricular systolic dysfunction. Ejection fraction and fractional shortening were significantly lower in the patient group at admission compared to controls (p = 0.013, p = 0.010, respectively). While the ejection fraction was <55% in eight patients, and global longitudinal strain was lower than -2SD in 29 patients at admission. Global longitudinal strain z-score <-2SD persisted in 13 patients at 2-month follow-up. Ejection fraction increased above 55% in 3.42 ± 0.53 days in 7 of 8 patients with left ventricular systolic dysfunction, ejection fraction was 51% at discharge in one patient, and left ventricular systolic dysfunction persisted at the 6-month of follow-up. CONCLUSION: These results confirmed that speckle tracking echocardiography is more likely to detect subclinical myocardial damage compared to conventional echocardiography. In addition, it is a valuable method for follow-up in this patient group.

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.

Myopericarditis with Significant Left Ventricular Dysfunction Following COVID-19 Vaccination: A Case Report.

BACKGROUND Since Emergency Use Authorization of COVID-19 vaccines in December 2020, more is becoming known about their adverse effects. Growing numbers of myopericarditis cases after COVID-19 vaccination are being reported, mostly in younger adults. While most of these patients have recovered rapidly and without complications, it is still unclear whether patients who are older and have greater cardiac dysfunction secondary to myopericarditis will also experience the same recovery. CASE REPORT We report the case of a middle-aged man with myopericarditis and significant left ventricular dysfunction after the second dose of the Pfizer/BioNTech BNT162b2 COVID-19 vaccine. He presented several days after vaccination, and with non-steroidal anti-inflammatory treatment, he quickly recovered ventricular function, and symptoms resolved within 1 week after vaccination. CONCLUSIONS Vaccines are a key tool in combating the COVID-19 pandemic, yet many people are hesitant to seek vaccination, perhaps for fear of adverse events. Our report of a middle-aged patient with significant left ventricular dysfunction, who still experienced rapid recovery, should reassure the public about the safety of vaccines. Such rare adverse effects should not deter people from receiving COVID-19 vaccination.

Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).

Cardiogenic shock with highly complicated course after influenza A virus infection treated with vva-ECMO and Impella CP (ECMELLA): a case report.

BACKGROUND: The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. CASE PRESENTATION: A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission. CONCLUSIONS: This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.

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.

Six Month Follow-up of Patients With Multi-System Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: Myocardial dysfunction and coronary abnormalities are prominent features of multisystem inflammatory syndrome in children (MIS-C). In this study we aim to evaluate the early and midterm outcomes of MIS-C. METHODS: This is a longitudinal 6-month cohort study of all children admitted and treated for MIS-C from April 17 to June 20, 2020. Patients were followed ∼2 weeks, 8 weeks, and 6 months postadmission, with those with coronary aneurysms evaluated more frequently. RESULTS: Acutely, 31 (62%) patients required intensive care with vasoactive support, 26 (52%) had left ventricular (LV) systolic dysfunction, 16 (32%) had LV diastolic dysfunction, 8 (16%) had coronary aneurysms (z score ≥2.5), and 4 (8%) had coronary dilation (z score <2.5). A total of 48 patients (96%) received immunomodulatory treatment. At 2 weeks, there was persistent mild LV systolic dysfunction in 1 patient, coronary aneurysms in 2, and dilated coronary artery in 1. By 8 weeks through 6 months, all patients returned to functional baseline with normal LV systolic function and resolution of coronary abnormalities. Cardiac MRI performed during recovery in select patients revealed no myocardial edema or fibrosis. Some patients demonstrated persistent diastolic dysfunction at 2 weeks (5, 11%), 8 weeks (4, 9%), and 6 months (1, 4%). CONCLUSIONS: Children with MIS-C treated with immunomodulators have favorable early outcomes with no mortality, normalization of LV systolic function, recovery of coronary abnormalities, and no inflammation or scarring on cardiac MRI. Persistence of diastolic dysfunction is of uncertain significance and indicates need for larger studies to improve understanding of MIS-C. These findings may help guide clinical management, outpatient monitoring, and considerations for sports clearance.

Strain Echocardiography and Myocardial Dysfunction in Critically Ill Children With Multisystem Inflammatory Syndrome Unrecognized by Conventional Echocardiography: A Retrospective Cohort Analysis.

OBJECTIVES: Multisystem inflammatory syndrome in children is a newly defined complication of severe acute respiratory syndrome coronavirus 2 infection that can result in cardiogenic shock in the pediatric population. Early detection of cardiac dysfunction is imperative in directing therapy and identifying patients at highest risk for deterioration. This study compares the strengths of conventional and strain echocardiography in identifying cardiac dysfunction in critically ill children with multisystem inflammatory syndrome in children and their association with ICU therapeutic needs and clinical outcomes. DESIGN: Retrospective, observational cohort study. SETTING: A large, quaternary care PICU. PATIENTS: Sixty-five pediatric patients admitted to the PICU with the diagnosis of multisystem inflammatory syndrome in children from March 2020 to March 2021. INTERVENTIONS: Global longitudinal strain four chamber was measured retrospectively by strain echocardiography and compared with conventional echocardiography. Cardiac dysfunction was defined by left ventricular ejection fraction less than 55% and global longitudinal strain four chamber greater than or equal to -17.2%. Clinical variables examined included cardiac biomarkers, immune therapies, and ICU interventions and outcomes. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients (37%) had abnormal left ventricular ejection fraction and 56 (86%) had abnormal global longitudinal strain four chamber. Between patients with normal and abnormal left ventricular ejection fraction, we failed to identify a difference in cardiac biomarker levels, vasoactive use, respiratory support needs, or ICU length of stay. Global longitudinal strain four chamber was associated with maximum cardiac biomarker levels. Abnormal global longitudinal strain four chamber was associated with greater odds of any vasoactive use (odds ratio, 5.8; 95% CI, 1.3-25.3; z-statistic, 2.3; p = 0.021). The number of days of vasoactive infusion was correlated with global longitudinal strain four chamber (r = 0.400; 95% CI, 2.4-3.9; p < 0.001). Children with abnormal strain had longer ICU length of stay (4.5 d vs 2 d; p = 0.014). CONCLUSIONS: Our findings suggest strain echocardiography can detect abnormalities in cardiac function in multisystem inflammatory syndrome in children patients unrecognized by conventional echocardiography. These abnormalities are associated with increased use of intensive care therapies. Evaluation of these patients with strain echocardiography may better identify those with myocardial dysfunction and need for more intensive therapy.

Myocarditis after Covid-19 Vaccination in a Large Health Care Organization.

BACKGROUND: Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored. METHODS: We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose. RESULTS: Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function. CONCLUSIONS: Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

Understanding the association between endothelial dysfunction and left ventricle diastolic dysfunction in development of coronary artery disease and heart failure.

Cardiovascular diseases (CVDs)  have been the most common cause of death worldwide for decades. Until recently the most affected patients were middle-aged and elderly, predominantly men, with more frequent ST elevation myocardial infarction  (STEMI) caused by obstructive coronary artery disease (CAD). However, in the last two decades we have noticed an increased incidence of ischemia with non-obstructive coronary arteries (INOCA), which includes myocardial infarction with non-obstructive coronary arteries (MINOCA) and non-myocardial infarction syndromes, such as microvascular and vasospastic angina, conditions that have been particularly pronounced in women and young adults - the population we considered low-risky till than. Therefore, it has become apparent that for this group of patients conventional methods of assessing the risk of future cardiovascular (CV) events are no longer specific and sensitive enough. Heart failure with preserved ejection fraction (HFpEF) is another disease, the incidence of which has been rising rapidly during last two decades, and predominantly affects elderly population. Although the etiology and pathophysiology of INOCA and HFpEF are complex and not fully understood, there is no doubt that the underlying cause of both conditions is endothelial dysfunction (ED) which further promotes the development of left ventricular diastolic dysfunction (LVDD). Plasma biomarkers of ED, as well as natriuretic peptides (NPs), have been intensively investigated recently, and some of them have great potential for early detection and better assessment of CV risk in the future.

COVID19-associated cardiomyocyte dysfunction, arrhythmias and the effect of Canakinumab.

BACKGROUND: Cardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive. AIMS AND METHODS: We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1ß antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy. RESULTS: Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca2+ transient amplitudes and altered baseline [Ca2+] upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca2+ release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca2+ release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca2+ release or Ca2+ signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity. CONCLUSION: Serum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca2+ signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca2+ imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein.

Cardiac pathology 6 months after hospitalization for COVID-19 and association with the acute disease severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase. METHODS: Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization. RESULTS: Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease. CONCLUSIONS: CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders. TRIAL REGISTRATION: COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232.

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).