Viral Infections Can Lead To Arrhythmias And Cardiac Deaths In Early Stages Of Infections Even Before Myocarditis Sets In!

Medical News: In recent groundbreaking research conducted by the Fralin Biomedical Research Institute at Virginia Tech Carilion-USA, a startling revelation has emerged about the intricate relationship between viral infections and the heart. Traditionally, the medical community has focused on the inflammatory response known as myocarditis, which often occurs as a result of the body's immune reaction to viral infections. However, this paradigm is shifting, as a study co-led by Dr James Smyth, an associate professor at the institute, has uncovered a previously unrecognized threat: viral infections create perilous conditions in the heart even before the onset of inflammation.


Viral Infections Can Lead To Arrhythmias And Cardiac Deaths In Early Stages Of Infections Even Before Myocarditis Sets In

So far, including in this ongoing COVID-19 pandemic, the focus has been on heart inflammation known as myocarditis, which is often triggered by the body's immune response to a viral infection. This new discovery suggests completely new directions to diagnose and treat viral infections affecting the heart.
 
Considering that the high incidence of viral-related myocarditis leading to sudden cardiac death, the insight is crucial. Up to 42% of sudden cardiac deaths in young adults are attributed to myocarditis, and of these cases viral infection is the leading cause.
 
Dr Smyth added, "From a clinical perspective, our understanding of viral infection of the heart has focused on inflammation, causing problems with the rate or rhythm of the heartbeat. But we have found an acute stage when the virus first infects the heart and before the body's immune response causes inflammation. So even before the tissue is inflamed, the heart is being set up for arrhythmia."
 
The Critical Discovery
This discovery challenges the conventional understanding of viral infections' impact on cardiac health, shedding light on a crucial early stage that precedes myocarditis. Smyth and his team, in their investigation focusing on adenovirus, a common instigator of cardiac infections and myocarditis, have unveiled how the virus itself sets the stage for potential cardiac issues before the body's immune response triggers inflammation.
 
Early Infection and Cardiac Disturbances
The study, co-led by virologist Dr Rachel Padget, utilized mouse adenovirus type-3 to replicate the human infection process. The findings indicate that in the early stages of infection, the virus disrupts crucial components of the heart's communication and electrical systems. Specifically, adenoviral infection disturbs gap junctions, tiny tunnels between heart cells facilitating communication, and ion channels, gates in cell membranes maintaining the necessary balance of ions for normal heart function. Even before noticeable symptoms manifest, these disruptions create an environment conducive to irregular patterns of electrical activity, known as arrhythmias, potentially leading to sudden cardiac problems, especially in individuals with active viral infections.
 
Implications for Diagnosis and Treatment
This paradigm-shifting research offers new avenues for both diagnosis and treatment of viral infections affecting the heart. Dr Smyth emphasizes the significance of targeting specific heart changes induced by viral infections at the molecular level to mitigate the risk of cardiac complications in those grappling with viral illnesses. By delving into the molecular intricacies, researchers aim to identify biomarkers that can indicate a higher risk of arrhythmias, potentially paving the way for simple blood tests in routine clinical settings.
 
Looking Beyond Traditional Diagnostics
The traditional diagnostic methods, such as MRI and echocardiography, may not reveal the early danger presented by viral infections. Dr Smyth explains that while individuals with acute infections may appear normal under these diagnostic techniques, molecular-level analysis provides a deeper understanding of the risks involved. He told Thailand Medical News, "Individuals who have acute infections can look normal by MRI and echocardiography, but when we delved into the molecular level, we saw that something very dangerous could occur.”
 
Consequently, the research opens up the possibility of developing more targeted and sensitive diagnostic tools, such as blood tests, to identify individuals at a higher risk of developing arrhythmias.
 
A Closer Look at the Research
The study, titled "Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis," delves into the molecular mechanisms underlying the acute phase of viral cardiac infection. Utilizing mouse adenovirus type-3 as a model, the researchers investigated the alterations to the infected heart before the onset of significant immune responses or visible cardiomyopathy. The results of optical mapping revealed a decrease in conduction velocity along with increased phosphorylation of Cx43Ser368, a residue crucial for gap junction function. Moreover, hearts with a phospho-null mutation at Cx43Ser368 demonstrated protection against adenoviral-induced conduction velocity slowing.
 
Human Relevance
The researchers extended their findings to human systems, demonstrating that human adenovirus type-5 increased phosphorylation of Cx43Ser368, disrupting synchrony in human induced pluripotent stem cell-derived cardiomyocytes. This alignment of findings across mouse and human systems emphasizes the common mechanisms underlying the arrhythmogenic substrate created by adenoviral infections.
 
Conclusion
In conclusion, this research by the has unveiled a previously overlooked aspect of viral infections, indicating that the heart faces potential dangers even before the onset of myocarditis. The findings provide a foundation for re-evaluating diagnostic approaches and developing targeted treatments to address the early stages of viral cardiac infections. By understanding the molecular alterations induced by the virus, healthcare professionals can potentially identify individuals at a higher risk of cardiac complications, paving the way for more proactive and personalized interventions. As the medical community continues to explore these new insights, the hope is to improve outcomes for individuals grappling with viral infections and mitigate the risk of cardiac-related complications, ultimately saving lives.
 
The key takeaway of the study is:  Viral infections such as adenoviral infections, creates an arrhythmogenic substrate through direct targeting of gap junction and ion channel function in the heart. Such alterations are known to precipitate arrhythmias and likely contribute to sudden cardiac death in acutely infected patients.
 
The study findings were published in the peer reviewed journal: Circulation Research.
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.122.322437
 
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