In this population-based cohort, established on hospitalization for myocarditis according to the Swedish NPR database, the following major findings were observed: 1) A slightly increased incidence of myocarditis per 100 000 inhabitants (from 6.3 in 2000 to 8.6 in 2014); 2) A decline in 1-year mortality in patients with myocarditis during 2000–2014; 3) An observed reduction in the mortality during the study period in patients ≥ 50 years of age.
The incidence of myocarditis in the general population is at present unknown. Studies have shown suspected myocarditis in 3.5-5% of patients during outbreaks of Coxsackievirus infection 7,12. The “golden standard” for diagnosis of myocarditis is endomyocardial biopsy. However, this is infrequently used, and has limited sensitivity 4,13. Autopsy studies have shown estimates of the prevalence of myocarditis to be 2–12% in those who died suddenly 14–16. Other studies reported myocarditis as a cause of initially unexplained DCM in 9% 17 and 10% in unexplained HF 9.
Our data showed a slight increment of incidence of clinical suspected myocarditis during a period of 15 years. Despite that endomyocardial biopsy is the diagnostic gold standard; it is seldom used in daily clinical practice, partly because of its low sensitivity 1, but also because myocarditis is often a self-limiting and mostly benign condition for which an invasive procedure is not warranted. Some guidelines recommend endomyocardial biopsy only in a limited number of clinical scenarios, including hemodynamic compromise, patients with life-threatening arrhythmia and those whose condition does not respond to conventional therapy 13. Therefore, noninvasive examinations and biomarkers are essential for the recognition of myocarditis in clinical practice. During the past few decades, the application of biomarkers has notably improved. Cardiac troponins are more sensitive to myocyte injury than creatinine kinase in patients with clinically suspected myocarditis 18,19. In Sweden, troponin T assay was introduced in 1997, which certainly contributed to better detection of myocarditis. However, the increased incidence of myocarditis cannot be sole explained by improvements in biomarker sensitivity, as the increasing trend could be seen already from when coverage for the NPR became nationwide in 1987 (data not shown). The increase might be attributable to other reasons, such as greater awareness among physicians of the myocarditis diagnosis, but also a possible real increase in myocarditis due to a rise in viral infections. Thus, our data may well indicate a true increase in myocarditis over the past decade.
Little information is available about the development of HF/DCM in patients with myocarditis. In our previous studies 20,21 we hypothesized that an increased incidence of myocarditis might at least partly account for the rise in the incidence of HF in the younger sector of the population. Moreover, some studies reported persistent cardiac dysfunction in about 25% of cases and either death or end-stage DCM in 12–25% 1–6,22,23. In the current study, we found that 6.4% of the patients with myocarditis developed incident HF/DCM within 1 year after the index hospitalization and 9.3% throughout the study period. The incident rates of HF/DCM were higher from 2000 to 2004, with 7.1% developing these conditions within 1 year after index hospitalization, compared with 5.8% in the last period. For patients ≥ 50 years of age, the incidence of HF/DCM was much higher, with 12% during the first year after the index hospitalization and approximately 19% during long-term follow-up, which is close to previously reported rates 1–6, 22,23. Of note, we observed a steadily decreased incidence of HF/DCM over time, which might be attributable to improved diagnosis and medical care of myocarditis, as well as of hypertension and ischemic heart disease which also causes HF. The highest risk of both HF/DCM and death occurred in the immediate post-discharge period after index hospitalization, in particular in those ≥ 50 years, suggesting that there is great potential for further improvement of acute care of myocarditis and subsequent follow-up.
Despite higher mortality in patients with myocarditis than in the reference population, mortality continued to decrease in the past decade (2000–2014). The declining trend in 1-year mortality in patients with myocarditis is probably multifactorial, partly attributable to earlier recognition of myocarditis and improved acute management, including HF treatment. Even though we noted a similar trend in mortality in the reference population, the fall was steeper in those diagnosed with myocarditis. The higher 1-year mortality in the myocarditis group, as compared with the reference population, indicates that myocarditis is not an entirely benign condition. Identifying the risk factors for cardiovascular death in patients with myocarditis is imperative and will be the focus of our future research.
Limitations and strengths
The main strengths of this study are access to data from practically all persons in Sweden and that the study covers an extended period. In Sweden, patients with suspected myocarditis based on symptoms and objective signs of cardiac dysfunction are routinely hospitalized. Almost all known myocarditis in Sweden during the study period are thus included in our database.
It is not possible to validate the individual diagnosis in nationwide register studies, which is a limitation. Still, in this study we performed diagnostic validation at the Sahlgrenska University Hospital in Gothenburg - a conglomerate of three hospitals at different locations in the city - every fifth year and records for all patients with a diagnosis of myocarditis. In this diagnosis-validated subpopulation, we showed a similar trend with an increasing incidence as in the overall cohort.
In conclusion, by having access to the Swedish national databases (for hospitalization, cause of death and the general population), we could show an increasing trend in the incidence of myocarditis over time but also a declining trend in both development of HF/DCM and mortality in these patients