Cardiovascular complications of influenza are often unrecognized. Common cardiovascular complications related to influenza virus infection include exacerbation of underlying heart disease, such as ischemic heart disease or heart failure. An uncommon cardiovascular complication is myocarditis, with an incidence of approximately 11% and in-hospital mortality of 24%.[5,6] The inflammation can extend to the pericardium, leading to myopericarditis. During the H1N1 influenza pandemic in 2009, 58 cases of associated myocarditis were identified worldwide; of these cases, fulminant myocarditis occurred in 36 patients (62%).
The diagnosis of myocarditis is based on clinical symptoms and diagnostic findings. The clinical symptoms of myocarditis include chest pain, dyspnea, and syncope. These symptoms generally begin a few days after an influenzalike illness. The diagnostic findings in myocarditis/myopericarditis are:
Serologic tests that reveal elevated cardiac enzyme (troponin and creatine kinase-MB) levels without evidence of an acute ischemic event
Transthoracic echocardiography or cardiovascular MRI that shows cardiac dysfunction, diffuse wall thickening, reduced ejection fraction, decreased wall motion, small cardiac chamber size, and pericardial effusion[1,7]
An abnormal ECG that shows diverse changes such as atrioventricular block, widened QRS complex, reduced R-wave height, abnormal Q wave, diffuse ST segment elevation, atrial fibrillation, supraventricular tachycardia, or ventricular fibrillation[1,8]
An endomyocardial biopsy that reveals cellular infiltration of mononuclear cells; cardiomyocyte rupture, fusion, and disappearance; and interstitial edema along with fibril formation (negative histopathologic examination results do not exclude the possibility of myocarditis, given the frequency of false-negative results)[1,9,10]
A PCR assay of a respiratory specimen that is positive for viral infection or a convalescent-phase viral antibody titer that is four times higher than the acute-phase titer
The pathophysiology of influenza-associated myocarditis is not completely understood. Direct viral invasion of the endocardium and an exaggerated immune response caused by severe influenza virus infection, with increasing interleukin levels[1,8,10] and an elevated tumor necrosis factor-alpha level, can result in myocardial injury.[3,9,11]
The management of myocarditis depends on treating the underlying cause, such as viral infection, along with treating the cardiac dysfunction and maintaining hemodynamic stability. Oseltamivir is an oral neuraminidase inhibitor approved for the treatment of influenza in patients who are symptomatic for 48 hours or less. However, treatment should be started in patients who are hospitalized with influenza regardless of the duration of symptoms. Early treatment with a neuraminidase inhibitor is the standard of care based on an observational study, because it decreases symptom duration.[13,14] Patients with influenza-related fulminant myocarditis usually require arteriovenous extracorporeal membrane oxygenation, an intra-aortic balloon pump, or percutaneous cardiac devices.[1,5] Although myocarditis is a rare complication of influenza, it should be rapidly identified in patients infected with influenza virus, as often these patients can develop fulminant myocarditis that requires circulatory support. Prompt initiation of such support is key to these patients' recovery.
Identifying patients who are at high risk for complications of influenza is imperative, and early initiation of empiric treatment, if influenza is suspected, is warranted in such patients. The following persons are at high risk for complications:
Children aged < 5 years and adults aged ≥ 65 years
Persons with chronic pulmonary disease (asthma), cardiovascular disease (excludes patients with a sole diagnosis of hypertension), chronic kidney disease, hematologic disease (eg, sickle cell disease), metabolic disorders (eg, diabetes mellitus), or chronic neurologic conditions (eg, stroke or epilepsy)
Persons with immunosuppression, including patients with HIV infection
Women who are pregnant or postpartum (within 2 weeks after delivery)
Persons with extreme obesity (body mass index of ≥ 40 kg/m2)
Patients in facilities (nursing homes, group homes)
Children and adolescents up to 18 years of age receiving aspirin- or salicylate-containing medication who are at risk for Reye syndrome after influenza virus infection
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