Cardiovascular manifestations associated with influenza virus infection

doi:10.1016/j.ijcard.2008.04.044

International Journal of Cardiology

Volume 130, Issue 3, 28 November 2008, Pages 304-309

https://doi.org/10.1016/j.ijcard.2008.04.044 Get rights and content

Abstract

Influenza accounts for 3 to 5 million cases of severe illness and up to 300,000 deaths annually. Cardiovascular involvement in acute influenza infection can occur through direct effects of the virus on the myocardium or through exacerbation of existing cardiovascular disease. Epidemiological studies have demonstrated an association between influenza epidemics and cardiovascular mortality and a decrease in cardiovascular mortality in high risk patients has been demonstrated following vaccination with influenza vaccine. Influenza is a recognised cause of myocarditis which can lead to significant impairment of cardiac function and mortality. With recent concerns regarding another potential global pandemic of influenza the huge potential for cardiovascular morbidity and mortality is discussed.

Introduction

Influenza is a debilitating respiratory illness which accounts for 3–5 million cases of severe illness and up to 300,000 deaths annually. Influenza pandemics are rarer events which occur every 10 to 50 years and during the 20th century at least 3 pandemics have occurred 1918, 1957 and 1968 [1]. The 1918 pandemic was the worst pandemic in history which killed more people than world war one with an estimated mortality between 50 and 100 million people [2]. It is widely believed that there will be another influenza pandemic before long. The next pandemic is expected to cause clinical disease in potentially billions of people. If the death toll associated with the 1918 influenza virus is translated to the current population, there could be 180 million to 360 million deaths globally documented [3]. Recent reports of an avian influenza strain, H5N1, which has caused multiple outbreaks in poultry on three continents and has infected several hundred people, killing more than half of them has raised concerns of another global pandemic especially because of intriguing parallels between the H5N1 virus and the 1918 influenza strain.

It is estimated that half of those infected with influenza virus have no clinical symptoms whilst in the remaining half clinical presentation varies from afebrile respiratory symptoms to febrile illness causing disorders affecting the lung, heart brain, kidneys and liver. Despite such a huge burden on morbidity and mortality worldwide and the potential for a future pandemic the cardiac manifestations of influenza infection have not been previously reviewed even though it is thought that a significant proportion of deaths from the global pandemics of the 20th century were due to cardiovascular causes. Furthermore it has been observed that during influenza epidemics in a number of population and clinical studies there is a marked increase in death rates from cardiovascular causes [4]. It is for this purpose that this review is written.

Section snippets

Influenza virus

Influenza A and B viruses are spherical or long shaped enveloped viruses with a segmented genome made of eight single stranded RNA segments of 890 to 2341 nucleotides each [5]. Influenza viruses hold generic status in the Orthomyxoviridae family and are classified into types A, B or C based on antigenic differences of their nucleo- and matrix proteins. They can be divided on the basis of the antigenicity of the surface proteins Haemaglutinin (HA) and Neuraminidase (NA). Influenza viruses are

Direct cardiac involvement in influenza infection

The frequency of myocardial involvement in influenza infection is variable with rates of up to 10% having been reported in the literature although this is dependant on the methods used to detect myocardial involvement. In a UK based study in which 152 patients were recruited from 60 primary health care centres with serological evidence of influenza infection [8] it was found that CK levels were elevated in 18 patients (12%). However none of these patients had clinical evidence of myocarditis

H5N1 avian influenza

The highly pathogenic avian influenza strain H5N1 has reached endemic levels among poultry in several South East Asian countries and reported cases have been described worldwide. H5N1 has crossed the species barrier in South East Asia, Africa and the Middle East with case fatalities reported in the order of 60% and continues to ignite global fears of a future pandemic [36]. Excellent reviews on H5N1 pathophysiology have been published recently which are beyond the scope of this review [36], [37]

Treatment

To date there have been no placebo controlled randomised trials in the treatment of influenza myocarditis, data has mainly been obtained from published case series. In a case series of 3 patients with influenza myocarditis [34] which were treated with intravenous ribavirin, it was demonstrated that influenza viral titres abruptly declined following initiation of drug therapy although 2 of the 3 patients in this series died shortly afterwards and the 3rd patient required left ventricular support

Influenza and coronary heart disease

A recent study investigated the impact of influenza epidemics on autopsy proven coronary deaths due to acute myocardial infarction and chronic ischaemic heart disease. Around 35,000 autopsy proven coronary heart disease deaths were recorded from 1993 to 2000 in St Petersburg, Russia. In each year studied peak coronary heart disease deaths were present and coincided with the influenza epidemic peak, and the odds ratio for acute myocardial infarction and chronic ischaemic heart disease deaths

Conclusion

In conclusion influenza accounts for up to 300,000 deaths annually and was responsible for around 50–100 million deaths worldwide in the global pandemic of 1918. With recent reported cases of human fatalities with the avian flu H5N1 influenza virus and its similarity to the influenza virus responsible for the 1918 global pandemic has raised concerns for another global pandemic. Cardiovascular involvement in acute influenza infection can occur through direct effects of the virus on the

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Influenza associated cardiac arrhythmia- a systematic review
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Influenza infection is rarely associated with cardiac conduction disorder. Cardiac arrhythmias due to such an infection have a full spectrum with ventricular arrythmias being the most common.
In our systematic review from PubMed, OVID Medline and EMBASE we have identified 23 articles describing arrythmias associated with different influenza infection. Most of them were case reports where ventricular arrhythmias were the most common.
Complete heart block after influenza infection is usually temporary and a permanent pacemaker is rarely needed. There are reports of Influenza associated with arrhythmias in adults, neonates, and even fetuses in pregnant woman. Different mechanisms were described in literatures by which influenza causes arrhythmias such as interleukin 6 & tumor necrosis factor-alpha mediated inflammatory response, sympathetic overactivation, focal myocarditis and cleavage of angiotensin converting enzyme 2 protein which is cardioprotective.
ACE 2 binder influenza viruses have more prone to be associated with cardiac conduction disorder. Oseltamivir for influenza infection is also associated with bradycardia and can shorten or lengthen QT segment. Influenza vaccination has found to be protective from cardiac arrhythmia.
Post-COVID myocarditis simulating acute coronary syndrome: Case report
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Acute myocarditis corresponds to an acute inflammation of the myocardium whose origin is most often viral. Several viruses can be incriminated to note the parvovirus B19, the virus herpes of the group 6 and to a lesser degree the virus of the hepatitis C (VHC). Since 2019 and with the discovery of SARS COV2 some cases of myocarditis associated with COVID have been noted, this last association is rare and is present in only 5% of cases. The diagnosis of myocarditis is sometimes difficult and can lead to confusion with acute coronary syndrome, especially in cases of ST-segment elevation on the EKG, hence the interest of magnetic resonance imaging, which has made it possible in recent years to reduce the rate of unnecessary coronary angiography, especially in the case of young subjects with no cardiovascular risk factors. Here, we report the case of a 33-year-old patient with no cardiovascular risk factors and no medical or surgical antecedents who was admitted to the emergency department for the management of acute chest pain, the patient had initially undergone an electrocardiogram which showed an ST-segment elevation in the inferior territory and in the low lateral territory with a mirror image in the high lateral territory. In view of the typical character of the pain and based on the electrical data, it was decided to carry out a coronary angiography which came back without any particularity. As part of the etiological work-up, an MRI scan was performed, which showed an appearance compatible with viral myocarditis. This case shows diagnostic difficulties and management of this disease.
Clinical characteristics and outcomes of mixed virus or bacterial infection in children with laboratory-confirmed influenza infection
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This study investigated the demographic characteristics and influenza complications of paediatric patients and explored the association of different influenza virus types and viral and bacterial coinfections with disease severity.
This retrospective cohort study used data collected in 2010–2016 from the Chang Gung Research Database (CGRD), the largest collection of multi-institutional electronic medical records in Taiwan. Data were retrieved for children aged 0–18 years with laboratory-confirmed influenza. We extracted and analysed the demographic characteristics and the data on clinical features, complications, microbiological information, and advanced therapies of each case.
We identified 6193 children with laboratory-confirmed influenza, of whom 1964 (31.7%) were hospitalised. The age of patients with influenza A infection was lower than that of patients with influenza B (4.48 vs. 6.68, p < 0.001). Patients with influenza B infection had a higher incidence of myositis or rhabdomyolysis (4.4%, p < 0.001) and a higher need for advanced therapies (OR, 1.96; 95% CI, 1.32–2.9, p < 0.001). In addition to bacterial (OR, 9.07; 95% CI, 5.29–15.54, p < 0.001) and viral coinfection (OR, 7.73; 95% CI, 5.4–11.07, p < 0.001), dual influenza A and B infection was also a risk factor for influenza complications (OR, 2.13; 95% CI, 1.47–3.09, p < 0.001).
Dual influenza A and B infection and bacterial coinfection can contribute to influenza complications. Early recognition of any influenza complication is critical for the timely initiation of organ-specific advanced therapies to improve influenza-associated outcomes.
A multicenter cohort study of severe dengue and critically ill influenza patients with elevated cardiac troponin-I: Difference clinical features and high mortality
2022, Travel Medicine and Infectious Disease
As cardiac involvement can cause serious complications and death, understanding its role in acute dengue and influenza virus infections is important.
We provide a comparative evaluation of severe dengue and critically ill influenza patients with elevated cardiac troponin-I (cTnI) from 2014 to 2019. Inclusion criteria included patients in which cTnI test were ordered. Patient without cTnI test was excluded.
During the study period, 82 (41 severe dengue and 41 critically ill influenza) patients had cTnI elevations, and 81 (35 severe dengue and 46 critically ill influenza) patients had a single normal cTnI test. Severe dengue patients with cTnI elevations had a significantly higher incidences of acute kidney injury, gastrointestinal bleeding, early mortality (≤7 after illness onset) and in-hospital mortality than those with severe dengue and single normal cTnI test. Significantly higher aspartate aminotransferase (AST) levels and higher incidence of gastrointestinal bleeding was observed in critically ill influenza patients with cTnI elevations compared to critically ill influenza patients with single normal cTnI measurement. Of the patients with cTnI elevations, the early and in-hospital mortality rates were 53.6% and 65.8%, respectively, in severe dengue patients, and 7.3% and 46.3%, respectively, in critically ill influenza patients. Significantly higher early mortality rates were observed in severe dengue patients with elevated cTnI levels than in critically ill influenza patients with cTnI elevations. Critically ill influenza patients with elevated cTnI levels had significantly higher incidences of pneumonia, pneumothorax, and bacteremia than severe dengue patients with cTnI elevations. Multivariate analysis revealed elevated AST (>1000U/L) (95% confidence interval [CI]: 1.690–143.174) was an independent risk factor for in-hospital mortality in severe dengue patients with elevated cTnI levels. Leukocytosis (95% CI: 1.079–1.124) and thrombocytopenia (95% CI: 2.739–5.821) were independently correlated with in-hospital mortality in critically ill influenza patients with cTnI elevations.
Differences in clinical features between severe dengue and critically ill influenza patients with cTnI elevations. High early mortality rate was observed in severe dengue patients with cardiac involvement. In contrast, most critically ill influenza patients died ≥2 weeks after the onset of illness, regardless of cTnI elevations. Our report has important clinical implications for the timely recognition and management of cardiac complication in patients with acute dengue and influenza virus infections.
Influenza update
2022, Viral, Parasitic, Bacterial, and Fungal Infections: Antimicrobial, Host Defense, and Therapeutic Strategies
Influenza is a highly contagious, viral respiratory tract infection that causes epidemics annually during winter months in temperate zones and periodic worldwide pandemics. It manifests as an acute febrile illness with variable degrees of symptoms and severity, ranging from mild fatigue, fever and cough, to respiratory failure and death. Laboratory testing is available to confirm the diagnosis of influenza. Most patients will recover with supportive care, but specific antiviral therapy is recommended for individuals with underlying medical conditions that place them at high risk for poor outcomes of influenza infection, as well as patients with severe disease. Annually, regular annual influenza vaccination is suggested for all persons aged ≥ 6 months who do not have a contraindication.
Prognostic impact of high sensitive troponin in predicting 30-day mortality among patients admitted to hospital with influenza
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Worldwide, seasonal influenza causes significant mortality and severe infections may cause cardiac injury. High-sensitive-troponins (hsTnT) are sensitive and specific markers of myocardial damage. This study investigated the prognostic impact of hsTnT on 30-day mortality in hospitalised influenza patients.
This retrospective study included influenza patients ≥ 18 years, who had hsTnT performed during admission in two tertiary-hospitals in South Australia. Diagnosis of influenza was confirmed by polymerase–chain-reaction (PCR) test and hsTnT > 14 ng/L with a change of > 20% during admission was considered to be indicative of acute-cardiac injury. Clinical characteristics, complications and 30-day mortality were compared among four groups of patients: hsTnT unavailable, hsTnT negative, chronically elevated hsTnT and acutely elevated hsTnT. Cox-proportional hazard regression determined the hazard of death at 30-days following hospital discharge after adjustment for co-variates.
Between January 2016 -March 2020, 1828 influenza patients, mean age 66.4 years, were hospitalised. Troponin results were available for 617 (47.7%) patients, of whom, 62 (10%) had acute myocardial injury and 232 (37.6%) had chronic hsTnT elevation. Both inpatient and 30-day mortality were significantly higher among patients with acute (P < 0.001) and chronic hsTnT (P < 0.001) when compared to other groups. When compared to patients with negative hsTnT, acute but not chronic hsTnT elevation was significantly associated with 30-day mortality after adjustment for various co-variates (HR 8.30, 1.80–17.84, P value = 0.013).
This is the largest available analysis of cardiac-specific biomarker hsTnT in patients with influenza. An acutely elevated hsTnT was associated with 30-day mortality among hospitalised influenza patients.

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ReviewCardiovascular manifestations associated with influenza virus infection

Abstract

Introduction

Section snippets

Influenza virus

Direct cardiac involvement in influenza infection

H5N1 avian influenza

Treatment

Influenza and coronary heart disease

Conclusion

Autoimmun Rev

JACC

Mod Pathol.

J Am Coll Cardiol

J Heart Lung Transplant

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

Am Heart J

Pandemic influenza and mortality: past evidence and projections for the future

Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic

Bull Hist Med

Preparing for the next pandemic

N Engl J Med

Architecture of ribonucleoprotein complexes in influenza a virus particles

Nature

Structured model of influenza virus replication in MDCK cells

Biotechnol Bioeng

The prevalence of myocarditis and skeletal muscle injury during acute viral infection in adults: measurement of cardiac troponins I and T in 152 patients with acute influenza infection

Arch Intern Med

Elevated serum myosin light chain I in influenza patients.

Intern Med

Surveillance for influenza admissions among children hospitalized in Canadian immunization monitoring program active centers, 2003–2004

Pediatrics

Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003–2004 season

Clin Infect Dis

Cardiac findings during uncomplicated acute influenza in ambulatory adults

Clin Infect Dis

Influenza A1 myocarditis in conscripts

Acta Med Scand

Idiopathic giant cell myocarditis—natural history and treatment

N Engl J Med.

Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology.

Circulation

Clinical manifestations of influenza a myocarditis during the influenza epidemic of winter 1998–1999

J Cardiol

Fulminant influenza type A associated myocarditis: a fatal case in an 8 year old child

Arch Mal Coeur Vaiss

Left ventricular pseudoaneurysm after acute influenza A myocardiopericarditis

J Cardiovasc Surg

A case of influenza subtype A virus-induced fulminant myocarditis: an experience of percutaneous cardio-pulmonary support (PCPS) treatment and immunohistochemical analysis

Tohoku J Exp Med

Influenza A virus infection complicated by fatal myocarditis

Am J Forensic Med Pathol

Review
Cardiovascular manifestations associated with influenza virus infection