Fulminant myocarditis represents a severe form of viral myocarditis, characterized by an abrupt onset and rapid clinical deterioration. Patients swiftly develop hemodynamic compromise (including pump failure and circulatory insufficiency) alongside malignant arrhythmias, resulting in an exceptionally high early mortality rate [6–7]. Endomyocardial biopsy remains the gold standard for definitive diagnosis. However, due to its inherent invasiveness, the diagnosis of fulminant myocarditis often relies on clinical features, biochemical markers, electrocardiographic findings, and echocardiographic characteristics.
Our study observed a diverse range of clinical presentations upon admission, with predominant extracardiac manifestations (gastrointestinal and respiratory) compared to circulatory symptoms. This aligns with previous international studies reporting fulminant myocarditis, often manifesting primarily through extracardiac symptoms [2]. Therefore, a high index of suspicion for fulminant myocarditis should be maintained in patients with a history of infection, after ruling out alternative explanations for these extracardiac manifestations. ECPR, also known as venoarterial ECMO, has demonstrated promising outcomes in fulminant myocarditis treatment. International literature reports a wider range of survival rates (33%-79%) for patients with fulminant myocarditis who underwent ECPR and were subsequently discharged [8–10]. However, our study's observed survival rate of 21.9% following ECPR falls below those reported internationally. This statistically significant difference (p < 0.05) may be attributed to the relatively recent development and potentially limited experience with ECMO technology in China.
Myocardial enzymes are proteins located within the heart muscle cells. When these cells are damaged or die (necrose or rupture), myocardial enzymes are released into the bloodstream. The levels of these enzymes indirectly reflect the extent of myocardial injury. CK-MB is a dimeric enzyme found predominantly in myocardial tissue. Its serum concentration exhibits a significant rise 3–8 hours following myocardial injury. The severity of the injury often correlates with the level of CK-MB, with values potentially exceeding those of healthy individuals by several fold. Cardiac troponin I is a myocardial cell-specific protein that binds calmodulin. It exists in both free and complex forms within human cardiomyocytes. Myocardial injury triggers its release into the bloodstream, leading to serum levels significantly higher than normal. While cTnI boasts high sensitivity, its return to normal levels can take 7–10 days. In this study, peak CK-MB and cTnI levels in the survival group differed significantly from those in the non-survival group. This finding suggests that a continuous rise in myocardial injury markers indicates disease deterioration, highlighting the importance of early intervention [11]. Furthermore, elevated AST and ALT were observed in most patients. This elevation may be associated with shock, congestive heart failure, or the viral triggers responsible for myocarditis itself. A pediatric study supports this association, reporting elevated AST levels in children with myocarditis [12, 13].
NT-proBNP has gained widespread use in clinical practice in recent years due to its high degree of cardiac specificity and sensitivity. This biomarker reflects left ventricular end-diastolic pressure, a measure of filling pressure within the heart's main pumping chamber. When ventricular volume or pressure load increases, leading to elevated wall tension, the synthesis and secretion of NT-proBNP rises accordingly. Consequently, NT-proBNP serves as an accurate indicator of changes in left ventricular function and is a key prognostic factor for assessing disease severity and patient outcomes [11]. Notably, this study found a significant difference (p < 0.05) in peak NT-proBNP levels between the survival and non-survival groups.
End-organ perfusion, a marker of tissue oxygenation, reflects the severity of hypoperfusion and aids in assessing circulatory shock. The kidneys, highly sensitive to ischemia and reperfusion injury, serve as an indicator of circulatory compromise. Scr is a well-established clinical measure of renal function. In fulminant myocarditis, reduced cardiac output, use of vasoactive medications, infection, hemolysis, and decreased blood volume can all contribute to renal dysfunction. Studies have demonstrated an association between Scr changes and mortality in adult fulminant myocarditis patients[14]. Our study observed that some patients received ECPR prior to ECMO, suggesting a rapid disease progression in the early stages, potentially leading to multi-organ dysfunction, particularly affecting the kidneys. Hypotension and systemic hypoperfusion before ECMO support in fulminant myocarditis patients can cause acute renal ischemia-reperfusion injury. Additionally, virus-mediated immune responses following the initial viral infection can also contribute to acute kidney injury. Consequently, changes in Scr may reflect both the severity of hypoperfusion and the intensity of the immune response, both of which can be confounding factors associated with poor prognosis[14].
Lactate, a byproduct of anaerobic glycolysis, plays a crucial role in metabolism and exercise. Its levels can not only detect abnormalities in the respiratory and circulatory systems but also reflect the severity of various conditions[15]. In critical care medicine, lactate has emerged as a risk factor for predicting patient mortality and a critical prognostic indicator [16, 17]. Elevated lactate levels can exacerbate heart failure and cardiogenic shock, ultimately contributing to increased patient mortality[18]. Our study observed a continuous rise in lactate levels within the non-survival group, with admission and peak levels exceeding those of the survival group (p < 0.05). Furthermore, logistic regression analysis identified peak lactate level as an independent risk factor for mortality in fulminant myocarditis. This aligns withprevious literature suggesting that peak lactate signifies severe myocardial damage and adversely affects patient outcomes[19–20].
ECG serves as a vital adjunct test in diagnosing fulminant myocarditis. In our study, approximately 90% of patients exhibited abnormal ECG findings. While previous literature suggests that a high-degree atrioventricular block on initial ECG may correlate with improved survival[2], Miyake et al. reported a poorer prognosis in patients with arrhythmias[21]. Notably, our study found a statistically significant difference (p < 0.05) in the incidence of VT/VF between the non-survival and survival groups, suggesting a potential association with worse outcomes in patients experiencing these arrhythmias. Echocardiography plays a valuable role in the early detection of cardiac enlargement, aiding in the diagnosis of fulminant myocarditis. This imaging modality allows for the evaluation of cardiac function and the exclusion of alternative etiologies, such as heart failure secondary to rheumatic or congenital heart disease, as well as valvular dysfunction. International studies have reported a poor long-term prognosis for patients with reduced left ventricular ejection fraction (LVEF)[18, 22]. While our data revealed lower LVEF and left ventricular fractional shortening (LVFS) in the non-survival group compared to the survival group, these differences did not reach statistical significance. This may be attributed to the relatively small sample size of our study.
Both domestic and international studies have demonstrated the efficacy of mechanical circulatory support therapy in reducing mortality rates for patients with fulminant myocarditis[23]. ECMO remains the most effective treatment option for fulminant myocarditis in children due to limitations in the pediatric medical device market and a paucity of relevant clinical research. Survival rates for patients with fulminant myocarditis treated with ECMO range from 64–83%[24–26]. Our study observed a slightly lower survival rate (57.9%) following ECMO treatment for fulminant myocarditis than previously reported data. Early and adequate administration of glucocorticoids has been shown to effectively suppress the immune response and potentially limit further myocardial cell damage[27]. While gamma globulin is currently used primarily as an immune-regulatory support therapy for fulminant myocarditis in children, existing evidence suggests that neither glucocorticoids nor IVIG have a significant impact on mortality rates[28, 29]. In this study, one patient presented with rapid disease progression upon admission. Despite implementing ECMO circulatory support following ECPR, the patient developed multiple organ failure, precluding the use of hormonal therapy or IVIG.
Study limitations
Due to the single-center, retrospective design and limited sample size, this study is susceptible to missing data and selection bias, potentially limiting the generalizability of its findings. Additionally, the absence of follow-up data precludes an evaluation of long-term outcomes in surviving patients after hospital discharge.