Acute myocarditis linked to higher 90-day all-cause mortality and adverse cardiac outcomes

1st November 2021

Acute myocarditis is associated with a high 90-day all-cause mortality and adverse cardiac outcomes including arrhythmias and cardiac arrest.

Patients hospitalised with acute myocarditis (MC) are at an increased risk of all-cause mortality, heart failure, arrhythmias and cardiac arrest compared to matched controls, according to research by a group from the Department of Cardiology, Aalborg University Hospital, Denmark. Inflammation of the cardiac muscle or myocardium (myocarditis) is typically seen in infants and teenagers but can occur at any age. Acute MC symptoms include a stabbing pain and or tightness in the chest which may spread across the body, shortness of breath with light exercise, difficulty in breathing at rest and even flu-like symptoms such as a high temperature, tiredness and fatigue. In addition, acute myocarditis has been shown to be a frequent cause of sudden death in men aged 18 to 28 years of age and in high school athletes. Although evidence points to favourable long-term outcomes in adults with myocarditis, the condition does appear to be associated with an increased risk of  cardiovascular and all-cause mortality within 3 months after discharge.

However, there is limited data on the short-term risks of MC, leading the Danish group to retrospectively analysis the outcomes for patients hospitalised with the condition. The researchers turned to the Danish Civil Registration System, which contains information on all registered Danish citizens and can be linked to other administrative databases. Patients were included in the analysis if they had been hospitalised with a primary diagnosis of MC between 2002 and 2018 or as a secondary diagnosis and with a primary diagnosis of heart failure (HF), ventricular tachycardia (VT), ventricular fibrillation (VF), cardiac arrest and cardioverter-defbrillator (ICD). These secondary diagnoses were used because the clinical diagnosis of MC may involve one of these other conditions. Those with myocarditis was age and sex-matched to a population of control patients without a diagnosis of prior MC in a 1:5 ratio. The primary outcome of interest was 90-day all-cause mortality and secondary outcomes were included 90-day presumed cardiovascular causes of death and 90-day risks for HF, a composite of VT or VF or cardiac arrest and ICD. The analysis involved regression modelling with hazard ratios adjusted for age, sex and co-morbidities.

Findings

A total of 15,138 patients were included in the analysis with 2523 with myocarditis who had a median age of 48 years (67.7% male). The 90-day all-cause mortality risk was 4.9% for those with myocarditis versus 0.3% for controls (p < 0.001), with an adjusted hazard ratio, aHR of 22.12 (95% CI 14.44 – 33.88). Similarly, the 90-day risk for  HF was 75 times higher (aHR = 75.29, 95% CI 42.54 – 133.23, p < 0.001), as was the risk for the VT/VF composite (aHR = 78.80, p < 0.01) and for ICD implantation (aHR = 65.56, p < 0.01).

Commenting on these results, the authors suggested the myocarditis is a serious disease that is associated with a significantly elevated short-term risk of death. They concluded that “patients with acute myocarditis may benefit from careful diagnostic work-up including cardiac monitoring in the early phase after diagnosis.”

Citation

MicroRNAs can distinguish between myocarditis and myocardial infarction

11th June 2021

Myocarditis can mimic myocardial infarction but a unique biomarker provides clinicians an opportunity to distinguish the two conditions.

Acute myocarditis (aMC) has many different causes but the prevalence is unclear because the condition has similar clinical symptoms to an acute myocardial infarction (aMI). Although the diagnosis of myocarditis can be confirmed with cardiac magnetic resonance imaging, this technique is not always available. However, one approach to resolve the diagnosis involves the use of microRNAs (miRNAs), which are small, non-coding RNAs that play an important role in gene expression. Several miRNAs have been identified in the infarcted heart and this led a team from the Vascular Pathophysiology Area, Madrid, to try and identify a unique miRNA which could be used to distinguish between myocarditis and myocardial infarction. The team focused on circulating T cells, in particular T helper 17 (Th17) cells, which were confirmed as being a characteristic of myocardial injury in the acute phase of myocarditis. They performed a miRNA microarray analysis and quantitative polymerase chain reaction (qPCR) assays in Th17 cells after experimentally inducing myocarditis and myocardial infarction in mice to identify unique biomarkers.

Findings
The researchers identified the miRNA, mmu-miR-721, produced by Th17 cells in mice which was only produced in response to either autoimmune or viral myocarditis and which was absent from those with aMI. Using four patient cohorts with myocarditis, they subsequently identified a human homologue to mmu-miR-721, termed has-miR-Chr8:96. The researchers found that plasma levels of has-miR-Chr8:96 were considerably higher among myocarditis patients compared to both those with a myocardial infarction and in healthy controls. The area under the receiver-operating characteristics curve for has-miR-Chr8:96 was 0.927 (i.e., 92.7%) for distinguishing between aMC and aMI and this diagnostic value was retained even after adjusting for age, ejection fraction, and serum troponin levels.

Although the authors accepted that more work is needed to validate this biomarker in other cardiac disorders such as dilated cardiomyopathy, their preliminary findings suggest that raised plasma levels of has-miR-Chr8:96 are unique to those with myocarditis and have sufficient discriminatory power from myocardial infarction.

Citation
Blanco-Dominguez R et al. A Novel Circulating MicroRNA for the Detection of Acute Myocarditis. N Engl J Med 2021;384:2014-27