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.

The Assessment of Myocardial Strain by Cardiac Imaging in Healthy Infants with Acute Bronchiolitis: A Systematic Review and Meta-Analysis.

This study aims to systematically review the incidence of myocardial strain detected by echocardiography in previously healthy infants with acute bronchiolitis and its role as a predictor for adverse outcomes in this setting. METHODS: Pubmed/Medline, Excerpta Medica Data Base (EMBASE), and Cochrane Library were searched in April 2020 to identify original observational prospective studies that systematically performed echocardiography for the screening of myocardial strain in healthy infants with acute bronchiolitis. Pooled estimates were generated using random-effects models. Heterogeneity within studies was assessed using Cochran's Q and I2 statistics. Funnel plots and Egger´s regression method were constructed to evaluate publication bias. Sensitivity analyses were also conducted to evaluate potential sources of heterogeneity. RESULTS: After a detailed screening of 305 articles, a total of 10 studies with 395 participants (mean of 40 participants per study) was included. Five of them were classified as high-quality studies. Up to 28% of cases presented adverse outcomes. The echocardiographic screening for myocardial strain was performed within the first 24 h of admission in 92% cases. Tissue Doppler imaging and Speckle-Tracking echocardiography were performed only in 20% of cases. The presence of pulmonary hypertension was evaluated with methods different from the tricuspid regurgitation jet in 64% of cases. Seven studies found some grade of myocardial strain with a pooled incidence of 21% (CI 95%, 11-31%), in the form of pulmonary hypertension (pooled incidence of 20% (CI 95%, 11-30%)), and myocardial dysfunction (pooled incidence of 5% (CI 95%, 1-9%)). The presence of these echocardiographic alterations was associated with adverse outcomes (pooled relative risk = 16; CI 95%, 8.2-31.5). After a subgroup analysis based on the echocardiographic techniques used, no significant heterogeneity across the studies was observed. There was no evidence of publication bias when assessed by Egger´s test. Cardiac biomarkers to assess myocardial strain were used in five studies. Only N-terminal-pro-brain natriuretic peptide accurately predicted the presence of myocardial strain by echocardiography. CONCLUSIONS: Myocardial strain is not infrequent in previously healthy infants with acute bronchiolitis, and it could be present at the early stages of the disease with prognostic implications. There is a need for sufficiently powered prospective studies with a similar methodology, preferably employing advanced imaging techniques, to conclusively address the usefulness of the assessment of myocardial strain in this setting.

Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy.

Dystrophin-deficient cardiomyopathy (DDC) is currently the leading cause of death in patients with dystrophinopathies. Targeting myocardial fibrosis (MF) has become a major therapeutic goal in order to prevent the occurrence of DDC. We aimed to review and summarize the current evidence about the role of the renin-angiotensin-aldosterone system (RAAS) in the development and perpetuation of MF in DCC. We conducted a comprehensive search of peer-reviewed English literature on PubMed about this subject. We found increasing preclinical evidence from studies in animal models during the last 20 years pointing out a central role of RAAS in the development of MF in DDC. Local tissue RAAS acts directly mainly through its main fibrotic component angiotensin II (ANG2) and its transducer receptor (AT1R) and downstream TGF-b pathway. Additionally, it modulates the actions of most of the remaining pro-fibrotic factors involved in DDC. Despite limited clinical evidence, RAAS blockade constitutes the most studied, available and promising therapeutic strategy against MF and DDC. Conclusion: Based on the evidence reviewed, it would be recommendable to start RAAS blockade therapy through angiotensin converter enzyme inhibitors (ACEI) or AT1R blockers (ARBs) alone or in combination with mineralocorticoid receptor antagonists (MRa) at the youngest age after the diagnosis of dystrophinopathies, in order to delay the occurrence or slow the progression of MF, even before the detection of any cardiovascular alteration.