ReviewCardiovascular manifestations associated with influenza virus infection
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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