Myocarditis: COVID mRNA is the largest drug cause

Created August 2025

Top 10 drugs most frequently associated with adverse events of myocarditis and pericarditis

Scientific Reports volume 15, Article number: 28849 (2025) https://doi.org/10.1038/s41598-025-13234-6

Jaehyeong Cho, Hyesu Jo, Jaeyu Park, Jeongseon Oh, Hyunjee Kim, Soeun Kim, Hayeon Lee, Yeona Jo, Jinyoung Jeong, Sooji Lee, Ho Geol Woo, Lee Smith, Guillermo F. López Sánchez, Sang Youl Rhee, Jee Myung Yang & Dong Keon Yon

Myocarditis and pericarditis are managed with various treatments, yet prior studies and case reports indicate that certain drug classes may elevate the risk for these inflammatory cardiac conditions. This research aimed to systematically identify the leading drugs most frequently associated with myocarditis and pericarditis cases.

Analyses were carried out using the global database of individual case safety reports from 1968 to 2024.

We identified the drugs most frequently reported in signal detection with myocarditis and pericarditis, selecting the top 10 drugs based on record count, excluding those used in the treatment of inflammatory cardiac conditions to avoid potential confounding. Two statistical indicators, the information component (IC) with IC025 and reporting odds ratio (ROR) with 95% confidence interval (CI) were used to conduct the disproportionality analysis in this study.

The following five drugs were consistently observed with both myocarditis and pericarditis: clozapine, mesalazine, smallpox vaccine, influenza vaccine, and COVID-19 mRNA vaccine.

The other leading drugs differed by condition, with nivolumab, pembrolizumab, ipilimumab, valproate, and metronidazole appearing more frequently for myocarditis, and ribavirin, sulfasalazine, methotrexate, omalizumab, and heparin for pericarditis.

Each of these drugs showed a significant signal detection with myocarditis (ROR, 83.22 [95% CI, 81.17–85.33]; IC, 3.96 [IC025, 3.94]) and pericarditis (42.16 [41.19–43.16]; 3.66 [3.64]). Although our findings did not allow for causal inference, these findings highlight the importance of monitoring for possible adverse carditis cases when prescribing these drugs. Further studies are encouraged to investigate underlying mechanisms, assess individual patient risk factors, and explore the long-term impacts associated with myocarditis and pericarditis in relation to drug.

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Myocarditis: definition and association with AFib and HRV - Perplexity AI Aug 2025

Myocarditis is an inflammatory condition affecting the myocardium (the middle muscular layer of the heart wall). This inflammation weakens the heart muscle and disrupts its electrical system, reducing the heart's ability to pump blood effectively. The condition affects approximately 10-20 people per 100,000 individuals worldwide, with an estimated 1.5 million cases occurring globally each year. heart+4

Causes and Risk Factors

The most common cause of myocarditis is viral infection , though the exact cause often remains unknown.

Major infectious causes include: mayoclinic+3

Viruses : COVID-19, influenza, adenovirus, coxsackie B, cytomegalovirus, Epstein-Barr virus, and hepatitis B/C webmd+1
Bacteria : Streptococcus, staphylococcus, and mycoplasma webmd
Parasites : Toxoplasma gondii and Trypanosoma cruzi webmd
Fungi : Candida and aspergillus webmd

Non-infectious causes include autoimmune disorders (lupus, rheumatoid arthritis), certain medications (chemotherapy agents, antibiotics), toxins (alcohol, cocaine), and rarely, COVID-19 vaccines. clevelandclinic+1

Risk factors include being male, young adult age, heavy alcohol consumption, chronic conditions like diabetes or HIV/AIDS, and certain medical treatments. clevelandclinic+1

Symptoms and Clinical Presentation

Many people with myocarditis have no symptoms or only mild ones. When symptoms occur, they include: heart+2

Chest pain (most common symptom) pennmedicine+2
Shortness of breath at rest or during activity pennmedicine+3
Fatigue and exercise intolerance heart+2
Rapid or irregular heartbeat (arrhythmias) mayoclinic+3
Lightheadedness or fainting mayoclinic+1
Flu-like symptoms including fever, headache, and body aches pennmedicine+3
Swelling in legs, ankles, and feet pennmedicine+2

Myocarditis and Atrial Fibrillation (AFib)

Yes, myocarditis is associated with atrial fibrillation. Research shows a significant connection between these conditions:

Clinical Evidence

Studies demonstrate that atrial fibrillation occurs in approximately 9% of patients hospitalized with acute myocarditis. When AFIB occurs alongside myocarditis, it significantly worsens outcomes: pmc.ncbi.nlm.nih

70% higher risk of in-hospital mortality (odds ratio 1.7) pmc.ncbi.nlm.nih
90% higher risk of cardiogenic shock (odds ratio 1.9) pmc.ncbi.nlm.nih
460% higher risk of cardiac tamponade (odds ratio 5.6) pmc.ncbi.nlm.nih
60% higher risk of acute kidney injury (odds ratio 1.6) pmc.ncbi.nlm.nih
Longer hospital stays and higher costs of care pmc.ncbi.nlm.nih

myocarditis and AFib

The relationship between myocarditis and AFIB occurs through several mechanisms: pmc.ncbi.nlm.nih

Direct viral injury to cardiac myocytes disrupting electrical conduction
Inflammatory processes causing cellular and extracellular matrix changes
Pericardial involvement leading to edema or ischemia from microvascular disease
Sympathetic nervous system activation creating a pro-arrhythmic state
Cytokine release (particularly interleukin-6) predisposing to AFIB development pmc.ncbi.nlm.nih

Myocarditis and AFib

COVID-19-associated myocarditis has been documented presenting as new-onset atrial fibrillation and heart failure without typical respiratory symptoms, highlighting that cardiac presentations may be the primary manifestation of viral myocarditis. pmc.ncbi.nlm.nih

Myocarditis and Heart Rate Variability (HRV)

Yes, myocarditis is strongly associated with altered heart rate variability. HRV serves as both a diagnostic tool and prognostic indicator in myocarditis:

HRV can predict myocarditis

Research demonstrates that ultra-short HRV measurements can predict clinical outcomes in myocarditis patients. Specifically: pmc.ncbi.nlm.nih

RMSSD < 10.72 ms was associated with:
- 14-fold higher risk of severe heart failure (adjusted odds ratio 14.056) pmc.ncbi.nlm.nih
- 9-fold higher risk of developing dilated cardiomyopathy (adjusted odds ratio 8.826) pmc.ncbi.nlm.nih
Model accuracy for predicting severe heart failure reached 86% using HRV parameters pmc.ncbi.nlm.nih

Mechanism of HRV Changes

HRV alterations in myocarditis result from: bmcanesthesiol.biomedcentral

Excessive sympathetic activation and parasympathetic inhibition
Autonomic nervous system dysfunction due to inflammatory processes
Reduced vagal activity correlating with disease severity
Inflammatory cytokines affecting cardiac autonomic control

Clinical Significance of HRV

HRV indices (particularly SDNN and RMSSD ) are significantly reduced in COVID-19 patients with myocardial injury compared to those without. This reduction correlates with: bmcanesthesiol.biomedcentral

Severity of left ventricular dysfunction jacc
Risk of ventricular arrhythmias aging-us
Overall prognosis and survival outcomes jacc+1

Arrhythmic Complications of Myocarditis

Ventricular arrhythmias occur in approximately 25% of acute myocarditis cases pmc.ncbi.nlm.nih+2
41% recurrence rate of major arrhythmic events during follow-up pmc.ncbi.nlm.nih+1
Sudden cardiac death affects up to 10.9% of myocarditis patients openheart.bmj+1

Cardiovascular Events – long term risk

Even patients with uncomplicated myocarditis face substantial long-term risks: academic.oup

42-fold higher risk of cardiovascular events compared to controls
Incidence rate of 43.7 events per 1000 patient-years vs. 0.9 in controls
6% recurrence rate of myocarditis episodes academic.oup
8.6% risk of developing pericardial disease academic.oup

Myocarditis Prognosis

The overall prognosis of myocarditis varies significantly: pmc.ncbi.nlm.nih

Mortality rate : approximately 4.4% overall, with fulminant cases having 26.7% mortality pmc.ncbi.nlm.nih
Recovery : Most patients with mild disease recover completely pmc.ncbi.nlm.nih+1
Chronic complications : 2-25% may develop dilated cardiomyopathy myocarditisfoundation+1
Recurrence : occurs in 10-15% of cases thecardiologyadvisor+1
Prognostic factors for worse outcomes include older age, poor functional status (NYHA class), lower albumin levels, and presentation with fulminant disease. pmc.ncbi.nlm.nih
References

Tags: Cardiovascular Virus