key: cord-0318594-sox9dr4b authors: Caycho Torres, M. d. C.; Clavo Yamahuchi, J.; Cornejo Ramos, C.; Diaz Gomez, K. A.; Zanoni Ramos, O.; Gayoso Liviac, A.; Ugarte-Gil, C.; Vega Zambrano, V. title: CARDIOVASCULAR DISEASES ASSOCIATED WITH INFLUENZA INFECTION: SYSTEMATIC REVIEW AND META-ANALYSIS date: 2021-08-13 journal: nan DOI: 10.1101/2021.08.11.21261941 sha: 96045557b2e473d762b110b5aca171baa3132769 doc_id: 318594 cord_uid: sox9dr4b Background: Cardiovascular diseases represent important diagnoses that can become fatal if an early and adequate management is not carried out. Since 1930, a possible relationship between these events and influenza virus infection has been proposed. Objectives: To determine the association between cardiovascular diseases and previous infection by influenza virus. Materials and methods: A systematic review was carried out according to PRISMA. The electronic search was carried out in the databases of EMBASE, PubMed, Global Index Medicus, Google Scholar and Cochrane Library. The included studies had laboratory-confirmed influenza in patients over 18 years of age; studies that considered pregnant patients or animals were excluded. The quality of the studies was verified using the standardized tool of the National Heart Lung and Blood Institute and the certainty of the results was assessed with GRADE. In addition, 2 meta-analysis of the association measures were performed using the Cochrane Software Review Manager 5.4.1. Results: 31 records were identified, of which 4 were included (n = 1101). These studies were conducted in Finland, China, and Australia. The estimated combined OR for the positive association between influenza A and acute myocardial infarction obtained was 2.52 (95% CI 1.59 - 4); and in the association with influenza B, an OR of 4.78 ( 95% CI 1.57-14.61). The OR obtained for the association with myocarditis was 5.23 (95% CI 1.00 - 27.32). Conclusions: Evidence of almost 5 times the risk of suffering acute myocardial infarction was found in those who had a previous episode of influenza B, and almost 3 with influenza A. Better quality longitudinal studies are required to confirm this finding. comorbidities than those without influenza infection. Acute myocardial infarction without ST elevation was observed in 90% of cases, while in those without influenza it was 74% (7). In another case series study in Ontario, Canada, a group of residents older than 35 years in whom infection with different respiratory viruses was found and were hospitalized for acute myocardial infarction in the interval from 2008 to 2015, 364 cases were found of acute myocardial infarction, of which 332 were positive for influenza and only 20 occurred within the risk range (7 days after respiratory infection). Higher risk was found in the first 3 days post infection, in cases of influenza B, in older patients and in patients with first hospitalization for acute myocardial infarction (8). An association between influenza infection and cardiac arrhythmias has been seen. For example, in a retrospective study carried out in Houston, Texas in 2019, it was seen that there is a significant correlation between high influenza activity and the incidence of ventricular arrhythmias that required shock treatment, in patients with implanted cardiac defibrillators (9). Another study carried out in Taiwan in 2016 indicates that unvaccinated patients with influenza are associated with a significantly higher risk of developing atrial fibrillation (AF), with an Odds ratio of 1.18 (p = 0.03). Whereas, in vaccinated patients, but without infection, the risk of atrial fibrillation was significantly lower with an Odds ratio of 0.88 (p <0.001). Finally, vaccinated patients who had the infection had an Odds ratio similar to patients who were not infected or vaccinated, with an Odds ratio of 1.14 (p = 0.21). It is concluded that influenza infection is significantly associated with the development of AF, with an 18% increase in risk, which can be reduced with vaccination (10) . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.11.21261941 doi: medRxiv preprint pandemic was greater than during the 2010 to 2011 season, 25 patients versus 4 patients, and the high prevalence of fulminant disease (17/29, 59%) was demonstrated in patients with myocarditis and influenza. (14) Pericardial involvement in the context of influenza has also been described as a complication, including cardiac tamponade in some case reports (15) ; however, there is little research in this regard and it may be an underdiagnosed condition. In the relationship between influenza and pericarditis, there were 2 cases reported in 2016 (16) and 2019 (17); In addition, a case associated with the use of the influenza vaccine was reported in 2018 (18) . In a study in Japan, in which 102 participants were evaluated from 2014 to 2017, only 2 cases of pericarditis were reported as a complication due to influenza infection confirmed by nasal swab (19) . The effect of increasing morbidity and complications in patients with heart failure and influenza infection is known. A cohort study showed an increase in hospitalizations for heart failure during the influenza season (20). In a 2020 meta-analysis that involved 6 cohort studies considering 179,158 patients, it was concluded that influenza vaccination was associated with a decrease in mortality in patients with heart failure (21). The last systematic review that analyzed a possible relationship between influenza infection and cardiovascular effects was in 2015 (5). Little by little, this relationship is becoming more known in the medical community; however, in recent years, recent studies have emerged that require evaluation. All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.11.21261941 doi: medRxiv preprint -To determine the association between cardiovascular diseases and influenza virus infection. -To determine the association between acute myocardial infarction and influenza virus infection. -To determine the association between atrial fibrillation and influenza virus infection. -To determine the association between pericarditis and influenza virus infection. -To determine the association between heart failure and influenza virus infection. -To determine the association between myocarditis and influenza virus infection. A systematic review will be carried out according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) (22) Eligibility Criteria We will include all patients over 18 years of age infected with any influenza virus serotype who had cardiovascular complications. We will consider those patients with diagnosis of influenza by serological tests or by any microbiological test: viral culture, rapid antigen detection test, reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence assays and rapid molecular detection assays. Patients with cardiovascular complications as elevated troponins, CPK-MB, pro-BNP, changes in EKG, acute myocardial infarction, cardiac tamponade, heart failure, cardiac arrhythmias. All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.11.21261941 doi: medRxiv preprint The association between influenza infection, vaccination, and atrial fibrillation: A nationwide casecontrol study Influenza Al Myocarditis in Conscripts Clinicopathologic Study of Thirty-Three Fatal Cases of Asian Influenza Elevated Serum Myosin Light Chain I in Influenza Patients A national survey on myocarditis associated with influenza H1N1pdm2009 in the pandemic and postpandemic season in Cardiac tamponade and heart failure as a presentation of influenza. Experimental and clinical cardiology An Interesting Case of Viral Pericarditis. Pediatric Emergency Care Influenza B virus infection complicated by life-threatening pericarditis: a unique casereport and literature review. BMC Infectious Diseases Recurrence of pericarditis after influenza vaccination: a case report and review of the literature The Prevalence and Findings of Subclinical Influenza-associated Cardiac Abnormalities among Preferred Reporting Items for Systematic Reviews and Meta-Analyzes: The PRISMA Statement Rayyan -a web and mobile app for systematic reviews Study Quality Assessment Tools | NHLBI, NIH Cochrane Handbook of Systematic Reviews of Interventions Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis