Content uploaded by Heiko Mahrholdt
Author content
All content in this area was uploaded by Heiko Mahrholdt on Apr 03, 2020
Content may be subject to copyright.
Review
Myocarditis in athletes: A clinical
perspective
Martin Halle
1,2
, Leonhard Binzenho
¨fer
1
, Heiko Mahrholdt
3
,
Michael Johannes Schindler
1
, Katrin Esefeld
1,2
and
Carsten Tscho
¨pe
4,5,6
Abstract
Myocarditis is an important cause of arrhythmias and sudden cardiac death (SCD) in both physically active individuals and
athletes. Elite athletes seem to have an increased risk for viral infection and subsequent myocarditis due to increased
exposure to pathogens (worldwide traveling/international competition) or impaired immune system (continuing training
during infections/resuming training early thereafter, strenuous exercise training or competition, and exercising in
extreme weather conditions). Initial clinical presentation is variable, but athletes characteristically express non-specific
symptoms of fatigue, muscle soreness, increased heart rate at rest, as well as during exercise and reduced overall
exercise capacity. Beyond resting electrocardiogram (ECG), cardiac biomarkers, echocardiography, and 24-hour
Holter ECG, diagnostic work-up should include cardiac magnetic resonance imaging (CMR) assessing inflammation,
oedema, and fibrosis by late gadolinium enhancement (LGE), respectively, as these measures are crucial for prognosis
and sports eligibility. For patients with insufficient cardiac recovery, endomyocardial biopsy is recommended to clarify
differential diagnoses and initiate specific treatment options. In uncomplicated cases with normal left ventricular function
during acute phase and absent LGE, eligibility for sports can be attested to three months after clinical recovery. In those
with persistent pathological findings, even after six months, the risk for SCD remains increased and resuming exercise
beyond recreational activities can only be recommended individually based on course of disease, left ventricular function,
arrhythmias, pattern of LGE in CMR, as well as intensity and volume of exercise performed during training and com-
petition. For all athletes, follow-up examination should be performed yearly.
Keywords
Myocarditis, exercise, physical activity, return to play, sports eligibility
Received 8 December 2019; accepted 8 February 2020
Introduction
Myocarditis is considered to be one of the most
common acquired causes of arrhythmias, myocardial
dysfunction, heart failure, and sudden cardiac death
(SCD) in young, otherwise healthy individuals.
1,2
Recommendations for preventative measures, as well
as advice for resuming physical activity and sports
after myocarditis, include assessment of exercise inten-
sity, establishing a stepwise training schedule, and
recommendations for eligibility in competitive sports.
These measures have only been discussed briefly in pre-
vious European and American recommendations.
3,4
Therefore, the aim of this clinical perspective is to sum-
marize the existing knowledge of exercise in the devel-
opment of acute myocarditis, and to extend the
1
Department of Preventive Sports Medicine and Sports Cardiology,
Technical University of Munich, Germany
2
DZHK (German Centre for Cardiovascular Research), partner site
Munich Heart Alliance, Germany
3
Department of Cardiology, Robert Bosch Medical Center, Stuttgart,
Germany
4
Department of Cardiology, Campus Virchow (CVK), Charite
´
Universita
¨tsmedizin Berlin, Germany
5
DZHK (German Centre for Cardiovascular Research), partner site
Berlin, Germany
6
Berlin Institute of Health/Center for Regenerative Therapy (BCRT),
Germany
Corresponding author:
Martin Halle, Department of Preventive Sports Medicine and Sports
Cardiology, School of Medicine, University Hospital Klinikum rechts der
Isar, Technical University of Munich, Georg-Brauchle-Ring 56, 80992
Munich, Germany.
Email: Martin.Halle@mri.tum.de
European Journal of Preventive
Cardiology
0(00) 1–11
!The European Society of
Cardiology 2020
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/2047487320909670
journals.sagepub.com/home/cpr
rationale for current recommendations for sports and
exercise training both during and after recovery. This
information applies to all individuals who perform
exercise, irrespective of whether they are involved in
competitive or recreational sports.
Potentially increased susceptibility for
myocarditis in athletes
The exact incidence of acute myocarditis in the general
population remains unclear, since undiagnosed and
asymptomatic cases defy a comprehensive statistical
analysis.
5,6
In athletes, myocarditis accounts for up to
8% of deaths, but incidence rate varies significantly
depending on the investigated cohorts.
1,7,8
Elite athletes in particular have a unique lifestyle
characterized by frequent international travel, leading
to increased exposure to a variety of pathogens and
accompanied by factors that may potentially impair
the athlete’s immune system (e.g. extreme climate envir-
onmental or high altitudes during competition).
Moreover, their immunological competence may be
impaired by sleep deprivation, jet lag, climate shifts,
and exhaustive exertion during long tournaments,
although scientific evidence for this remains equivocal.
9
Continuing training or competition despite symptoms
of common cold infection may be an additional factor,
which, when combined (Figure 1), may pave the way
for various pathogens to trespass physical barriers,
spread systemically, and affect the myocardium.
Evidence from animal models
In the absence of data determining the effect of exercise
in the context of active myocarditis in humans, animal
studies have sought to illuminate immunological
features and clinical course of the condition. Mouse
models with CVB3 myocarditis have revealed an exer-
cise-induced increase of viral titers,
10,11
a threefold
increase in the number of cytotoxic T-cells when exer-
cise was initiated after 48 hours of viral infection,
12
and
an augmented myocardial necrosis,
10,11
accompanied
by significantly increased mortality in most
10,11,13
but
not all studies.
12
Particularly strenuous exercise during
the early phase (within nine days of viral myocardial
infection) has shown to aggravate pathophysiological
mechanisms and significantly worsen clinical out-
come.
10,11,13
The clinical course seems to be affected
to a lesser extent during the latter phase (>9 days),
when viral load diminishes.
11
These data, however,
Figure 1. Factors increasing susceptibility of infection and potential myocarditis in athletes.
2European Journal of Preventive Cardiology 0(00)
are limited to animal studies and may not be applicable
to humans.
Aetiology
Viral infections of the upper airways and of the
gastrointestinal tract are the most common pathogens
to cause acute myocarditis. Endomyocardial biopsy
(EMB) samples have revealed adenovirus (AV), enter-
oviruses (e.g. CVB3, cytomegalovirus), parvovirus B19
(B19V), and Human Herpesvirus 6 (HHV6) to be the
most frequent causes. Persisting cardiac B19V and
HHV6 virus may pose the potential for latent infection;
however, the mere presence of B19V specifically does
not automatically indicate a trigger for myocarditis,
since B19V DNA can also be found non-pathogenically
in nearly all organs, including in those of healthy indi-
viduals. Less prevalent causes include bacterial, fungal,
and protozoal infections.
14,15
In suspected cases of
myocarditis, a thorough travel history must be con-
ducted in order to assess for schistosomiasis (primarily
in Africa, but also in Japan, China, Middle East, South
America, the Caribbean; no direct infiltration of worms
into pulmonary artery or myocardium, but indirect
inflammatory or immune-reaction-induced vascular,
e.g. pulmonary artery or myocardial, manifestation),
Chagas disease (North America, Europe, Japan,
Australia), tuberculosis (Asia and Africa, Eastern
Europe), or hepatitis C (Japan). In athletes performing
outdoor sports, Lyme disease (borreliosis) is also a
common diagnosis. Non-infectious diseases, such as
inflammatory bowel disease, rheumatoid arthritis,
collagenosis, vasculitis, and idiopathic forms (e.g.
giant-cell myocarditis, sarcoidosis) should also be con-
sidered.
6,14
Moreover, antibiotics, diuretics, tricyclic
anti-depressants, cocaine, or doping substances such
as amphetamines, dissociation curve modulators, and
anabolic agents can potentially induce myocardial
inflammation or cardiomyopathy (Figure 1).
16–18
Clinical presentation
Symptoms of acute myocarditis are highly variable and
rather non-specific, if not completely absent. Although
clinical findings in both physically active and sedentary
individuals with acute myocarditis are similar, athletes
are usually more alert to subtle disease symptoms that
are either commonly neglected or not perceived at all in
inactive subjects, due to their sedentary behaviour and
lower body awareness (Table 1). These symptoms
include increased fatigability, minor declines in physical
performance, myalgia, headache, mild depressive symp-
toms, or new onset of atrial or ventricular arrhythmias,
which may cause light-headedness, dizziness, or even
pre-syncopal symptoms, particularly in endurance
athletes with resting heart rates of 50 beats per
minute (BPM) or less. Peripheral muscle soreness unre-
lated to exercise training or overall body discomfort
may be present at rest or after training. An increase
in heart rate of 5–10 BPM at rest or during standar-
dized exercise may be recognized, indicating potential
subclinical infection. The more infrequent cases of
severe myocarditis initially present with dyspnoea on
exertion, post-viral-induced fatigue syndrome, signs of
heart failure, or cardiogenic shock, as well as rhythm
abnormalities or even aborted SCD.
14
Diagnostics in athletes
Typical electrocardiogram (ECG) findings are ventricu-
lar and supraventricular arrhythmias, multiple-lead ST-
elevation in associated pericarditis, T-wave inversions,
left-bundle branch block, ventricular ectopy, high-
grade AV block, and low voltage resulting from peri-
cardial effusion or myocardial oedema.
3,19
In some ath-
letes with acute myocarditis, however, the ECG
remains completely normal. Moreover, differential
diagnosis can be more complicated in elite endurance
athletes with ‘‘athlete’s heart’’, as characteristic ECG
findings of cardiac adaptation to long-term exercise
are similar to findings in myocarditis (e.g. low-grade
AV block, sinus bradycardia, or ST-elevations in pre-
cordial leads V2 and V3).
20
If a previous routine ECG
is available, a careful comparison with the present find-
ings should be made. A 24-hour Holter ECG may
reveal rhythm abnormalities that can reveal ventricular
arrhythmias uncommon for athletes in terms of morph-
ology and complexity. These abnormal arrhythmias
will have to be differentiated from those with primarily
benign prognosis (for detail, see Corrado et al.
21
).
Therefore, a 24-hour Holter ECG should be pursued
in the course of a complete cardiac work-up in athletes
when myocarditis is suspected, as well as in follow-up
examinations in confirmed cases.
Assessing cardiac biomarkers for establishing diag-
nosis and tracking recovery is generally regarded as
standard of care, particularly as the ECG may still
be normal. Laboratory findings include elevated tropo-
nin T/I and CK/CK-MB, as well as elevated inflam-
matory markers. In athletes, it is noteworthy that
high-intensity training or strenuous competition may
physiologically induce several-fold increases of cardiac
biomarkers such as CK, CK-MB, troponins, and myo-
globin and natriuretic peptide levels (even into the
pathological range). However, these should normalize
within 48 hours post exercise and stay prolonged
elevated in myocarditis.
22
Viral serology is currently
not recommended as part of the standard diagnostic
work-up due to prominently occurring false-negative
results.
Halle et al. 3
Echocardiography is a key component of the stand-
ard diagnostic work-up for myocarditis. One of its
major advantages is the detection of pericardial effusion
as in (peri-)myocarditis or regional and global impair-
ment of left ventricular contractility (regional or global
dysfunction, or hypokinesia). Abnormal results from
strain analysis indicate cardiac inflammation with
oedema, especially when contractility is still pre-
served.
23
However, dilation of the left ventricle in elite
endurance athletes should not be mistaken as a sign
of acute myocarditis or as a basis for the definitive
diagnosis of myocardial disease. In ‘‘athlete’s heart’’,
left ventricular end-diastolic diameters (LVEDD) of
up to 60–65 mm may still be physiological in highly
trained male elite endurance athletes.
24
In addition, in
athletes with significant bradycardia, resting echocardi-
ography may reveal mildly impaired left ventricular
ejection fraction (LVEF), which, in athletes, immedi-
ately resolves during a short bout of exercise. If myo-
cardial function of the right ventricle is impaired and
the right ventricle dilated, arrhythmogenic right ven-
tricular cardiomyopathy has to be included in the list
of differential diagnoses of myocarditis. Nonetheless, a
sound history of exercise volume over the last years,
adjustment of LVEDD for gender and body size, and
comparisons to previous echocardiographic assess-
ments are important to differentiate physiological
from pathological findings.
20,24
Beyond echocardiography, cardiac magnetic res-
onance imaging (CMR) is the gold standard in non-
invasive diagnostics to quantify tissue characteristics,
and is crucial in patients with suspected acute myocar-
ditis.
6,25–27
Because of recent advances in relating CMR
findings to prognosis, the assessment of suspected
Table 1. Risk factors for increased risk for myocarditis and specific presentation of symptoms
in athletes.
Risk factors Stress factors by travelling
Jet lag
Time shift
Climate zone shift
Sleep deprivation
Increased exposure to pathogens
Frequent worldwide travel
Competition site with communal housing and canteens
Travel in buses between competition sites
Extreme environmental conditions
Cold (e.g. snow and ice sports)
Heat (e.g. high temperatures during the summer)
Extreme environments (e.g. desert runs)
Altitude (e.g. skiing and mountain climbing)
Low humidity (reduction of airway barrier)
Competition
High mental stress
High and repetitive intensive exercise strain
Reduced recovery time
Exercise despite early signs of infection
Medication
Illicit drugs (e.g. cocaine)
Doping agents (e.g. amphetamines and anabolic steroids)
Increased risk of depressive symptoms (e.g. tricyclic antidepressants)
Symptoms Increased body awareness
Perception of subtle disease symptoms
Subtle fatigability at rest and during exercise
Perception of arrhythmias
Presentation of uncommon symptoms
Exaggerated muscle soreness
Reduced submaximal and maximal exercise capacity
Prolonged presentation of unspecific symptoms after infection
Increased heart rate
at rest (e.g. 5 beats/min) and in 24-hour Holter ECG
during exercise (e.g. 5–10 beats/min)
4European Journal of Preventive Cardiology 0(00)
myocarditis by CMR has been proposed as a core diag-
nostic tool for clinical work-up as well as risk predic-
tion in athletes.
26
It is of particular value in patients
and athletes beyond echocardiography, as late gado-
linium enhancement (LGE) and tissue characterization
techniques provide prudent diagnostic information
characteristically for myocarditis.
25,28
Changes in
CMR are best detected at 7–14 days within the course
of disease, as depicted by myocardial oedema or LGE.
The sensitivity of LGE alone to detect myocarditis is
approximately 50–60%; in combination with the assess-
ment of cardiac morphology and function sensitivity,
however, the sensitivity increases to 83%.
29
Novel tools
in CMR technology (e.g. T1 and T2 mapping for
assessing relaxation times and detection of extracellular
volumes (ECVs)) are very sensitive markers beyond
classical LGE imaging. In these cases, T1 mapping
can detect and quantify even small areas of fibrosis,
whereas T2 mapping can quantitatively detect myocar-
dial oedema, enabling discrimination between acute
and chronic pathologies,
25
findings which may also be
a prognostic criterion.
27
Recent data have revealed that
ECV calculation by T1 mapping does not only yield
higher diagnostic accuracy, but also has a prognostic
value, even in LGE negative but clinically suspected
myocarditis.
30
Moreover, the assessment of LGE visu-
ally or semi-quantitatively can both increase the accur-
acy of determining prognosis, although the predictive
value is limited (hazard ratio 1.05, 95% confidence
interval: 1.02–1.08, p¼0.001).
31
Healing of myocarditis
can be monitored by native myocardial T1 and T2
measurements, without the need for contrast media.
32
The association between the presence of LGE and
increased risk of cardiac mortality, as well as all-cause
mortality (including SCD), although only assessed in
few studies so far, makes CMR the key diagnostic
tool in the assessment of acute myocarditis.
27,29,33
Impairment of LVEF alone significantly increases mor-
tality. Positive LGE findings indicate increased cardiac
risk (MACE: death, heart failure decompensation,
heart transplantation, sustained ventricular arrhythmia
(>30 s), recurrent acute myocarditis) despite adequate
left ventricular (LV) function.
27
These findings also
indicate an increased MACE in patients with LVEF
40% from 1.1 to 2.6%, and in patients with LVEF
<40% from 6.4 to 10.5%. In those with mild impair-
ment (LVEF 40%) and absent LGE, mortality risk is
0.4% and increases to 1.2% with LGE, and further to
2.8–3.1% in those with LVEF <40%, depending on the
absence or presence of LGE.
27
Moreover, the negative
predictive potential of CMR, and especially LGE, is of
high clinical importance, as patients with biopsy-
proven myocarditis but normal CMR (LVEF >60%,
left ventricular end-diastolic volume <180 ml and no
LGE) have excellent prognoses.
29,34
Changes in the presence and size of LGE during the
first six months of disease also add to predicting clinical
outcomes. In a recent registry analysis (ITAMY:
ITAlian study in MYocarditis), compared to imaging
during the early phase of myocarditis, the number of
LGE segments decreased in 46%, remained unchanged
in 31% and increased in 14% of CMR, the latter being
associated with the worst prognosis.
35
Moreover, both
native myocardial T1 and T2 provide an excellent per-
formance for assessing the stage of myocarditis by
CMR.
32
These findings indicate that the reassessment
of LGE after six months may be of additional value for
risk prediction.
Furthermore, the volume and character of the LGE
pattern seems to be of prognostic value, although a
more ‘‘benign’’ pattern does not exclude the potential
of life-threatening arrhythmias. LGE with a spotty pat-
tern at inferior insertion point of the right ventricular
free wall to the interventricular septum seems to be
rather benign in contrast to a stria pattern, which is
associated with increased life-threatening arrhythmias
and cardiac sudden death.
36
Moreover, the localization
of LGE within the myocardium is of prognostic signifi-
cance with an (antero)-septal mid-wall patchy LGE
pattern, which is associated with a less favourable clin-
ical outcome as compared to other LGE patterns (e.g.
infero-lateral location linear/diffuse epicardial pat-
tern).
27,35,37
Antero-septal mid-wall patchy LGE pat-
terns are also associated with a more than twofold
increase in a patient’s risk for clinical cardiac events.
37
A positive LGE in CMR in athletes is, however, not
pathognomonic for acute myocarditis, as myocardial
fibrosis is found in up to 12% of middle-aged, leisure
time, asymptomatic athletes.
38
In particular, long-term
endurance exercise may induce fibrosis at the hinge
points between the right ventricle and interventricular
septum. It is still unclear whether this fibrosis is due
either to (a) previous silent and/or de novo myocarditis,
(b) reactivation of virus activity after a primary infec-
tion in early childhood, or (c) repetitive and prolonged
myocardial strain and maladaptation due to lifelong
endurance training.
39,40
Under the view of the environ-
mental and immunological challenges of elite athletes
(Figure 1 and Table 1), the reactivation of viral infec-
tion and subsequent fibrosis in elite endurance athletes
may be a plausible, albeit unproven, explanation.
Overall acute myocarditis can be diagnosed with high
sensitivity (84–96%) using multiple diagnostic tools in
conjunction with one another.
25
These approaches are,
however, not sufficiently sensitive in chronic myocarditis
cases to exclude chronic inflammation via negative
results (sensitivity of T2 mapping 77%; native T1 map-
ping 54%).
41
Considering the high susceptibility and severe conse-
quences of undiagnosed myocarditis in elite athletes,
Halle et al. 5
the threshold for pursuing early diagnostic procedures
(including ECG, echocardiography, and laboratory
testing for cardiac markers and inflammation with
repetition after 72 hours of pausing exercise) should
be lower as compared to physically inactive subjects.
These diagnostics should be pursued even in athletes
with only subtle perception of general symptoms –
regardless of whether these symptoms are acute or pro-
longed. Most importantly, for both diagnostic reasons
and for recommendations of eligibility for exercise
training or competition, the indication for CMR
should be broadly considered, even in patients with
normal LV function. This is especially important
since a normal CMR is indicative of a favourable prog-
nosis independent of clinical symptoms and other find-
ings.
29,34
In the chronic phase of the disease, a negative
CMR result cannot rule out the persistence of an
ongoing cardiac low-gradient inflammation, which
can have a prognostic impact over time. Furthermore,
chronic myocarditis should be included in the differential
diagnosis of ‘‘overtraining syndrome’’, a poorly defined
disease entity observed in athletes after overload of pro-
longed and intensive periods of exercise training, accom-
panied by reduced regeneration periods.
42
Therapy in athletes
The principles of myocarditis treatment in (elite) ath-
letes or those performing recreational exercise and
sports are not different from the general patient popu-
lation
6,43
(Figure 2). They are rooted in general
approaches of heart failure and antiarrhythmic ther-
apy. In EMB virus-positive myocarditis specific anti-
viral therapy (e.g. HHV), immunomodulation (e.g.
AV and enterovirus) or immunosuppression (e.g.
B19V) may be considered. Immunosuppression is man-
datory for virus-negative giant-cell, eosinophilic,
lymphocytic or sarcoid myocarditis, or myocarditis
secondary to autoimmune disease. It is important to
recognize and treat giant-cell myocarditis promptly,
because its course is often fulminant and can be fatal.
In Lyme disease, which often induces AV block, anti-
biotic therapy can lead to full recovery. Therefore, the
implantation of pacemakers or defibrillators should be
deferred beyond the acute phase.
The only current diagnostic tool capable of verifying
the aetiology of myocarditis is EMB with tissue ana-
lysis.
6,43
Histology and immune-histochemistry may be
applied, as well as polymerase chain reaction analysis to
directly detect viral genomes.
6
The procedure is recom-
mended in patients with acute myocarditis and (pre)car-
diogenic shock (class I recommendations
44
)orin
patients with arrhythmias and/or impaired LVEF, des-
pite conservative therapy for more than three months
(class II A recommendation
44
) to identify prognostically
relevant inflammation and aid in selecting treatment
options (e.g. giant-cell myocarditis). After exclusions
of the persistence of cardiotropic viruses, prednisone
plus azathioprine regimes are often used for up to six
months (e.g. methylprednisolone (initial dose 1 mg/kg,
after two weeks, decrease by 10 mg, and then another
10 mg every two weeks until 10 mg maintenance dose
(all together, six months) plus azathioprine (50–150 mg
for six months; accompanying treatment: proton
blocker, calcium 1 g/24 h)). In virus-positive patients,
treatment recommendations are not well established
(for a review, see Tschope et al.
43
). In these cases, the
differentiation between primarily cardiotropic viruses
3. Inflammation positive
Virus positive
2. Inflammation positive
Virus negative
Adenoviruses,
Enteroviruses
Immunmodulation with
Interferons possible
1. Inflammation negative
Virus negative
EMB results Differential diagnosis Therapeutic options
Post MC
Dilated cardiomyopathy
Heart failure therapy
Risk-adjusted therapy
Lymphocytic MC
Giant Cell MC
Sarcoid MC
Eosinophilic MC
Immunosuppression according
to tailored protocols
Herpesviridae
Parvovirus B19
Immunoglobulins or antivirals
in selected cases
Immunglobulins or
immunosuppression in
selected cases
Figure 2. Treatment algorithm in acute myocarditis (MC) depending on endomyocardial biopsy (EMB).
6European Journal of Preventive Cardiology 0(00)
(e.g. entero- and adenoviruses) and bystander viruses
(e.g. B19V, HHV6) is important. Entero- and adeno-
virus-induced myocarditis can be treated by immune
globulins or interferons. Bystander-associated myocar-
ditis forms most probably do not a specific anti-viral
therapy.
45
However, in selected no-option cases, anti-
viral therapy may be used.
Recommendations for exercise eligibility
Athletes with an uncomplicated course of acute myo-
carditis and complete recovery, including normal LV
function without LGE, have excellent prognosis.
27,34
In these cases, physical activity beyond moderate inten-
sity (as in cardiac rehabilitation or recreation, which
may be recommended as early as one month post-
acute phase with normal re-evaluation) can mostly be
resumed after three months
3,4
(Figure 3). This recom-
mendation also applies to pericarditis without signifi-
cant myocardial involvement.
Athletes with impaired LV function during the acute
phase, even with complete recovery, should be advised
to refrain from structured high-intensity training
or competitive sports for at least six months
3,4
(Figure 3), as long-term effects on myocardial function
remain uncertain depending on persistence of viral load
and chronic inflammation. Before starting exercise, a
thorough cardiological evaluation – for example, echo-
cardiography and 24-hour Holter ECG, including
a maximal exercise test and, optimally, a cardio-
pulmonary exercise test with spirometry (CPET) – has
to be performed to determine maximal exercise capacity
and exercise intensity thresholds. If results are normal,
athletes are eligible for sports, but, from our point
of view, should be advised to first start with moderate-
intensity (50–70% maximum oxygen uptake (VO
2max
))
endurance exercise for 4–6 weeks before higher-
intensity exercise is resumed. If this is tolerated well
for two months, full eligibility for competitive sports
can be approved in most cases.
In athletes with persistently reduced LV function
beyond six months, despite optimal medical heart fail-
ure therapy, eligibility for competitive sports cannot
be attested to, but moderate-intensity exercise can be
safely resumed, according to recommendations based
on studies of exercise in heart failure patients.
46
Thereafter, depending on the subsequent course of
recovery and type of sports, eligibility may be attested
to, but only on an individual basis with close monitor-
ing (Figure 3). The reasons for this approach are based
on the findings that the combination of impaired EF
and positive LGE has the worst prognosis, with a
Normal Abnormal
Non-eligible for any competitive sports
and exercise of moderate to vigorous
intensity for ≥6 months. Restricted to low
to moderate intensity rehabilitation
exercise on an individual basis
Non-ischemic
LGE positive or EF impaired or both
No signs of inflammation,
LGE negative, normal EF
Cardiac MR Imaging (CMR)
Suspected diagnosis of myocarditis in an athlete
according to medical history and symptoms
Persisting symptoms
Complete recovery
(symptoms,
cardiological work-up
including maximal
exercise test/CPET)
Eligible for any exercise and
competitive sport (start with
individually tailored recovery
programme).
Diagnosis of myocarditis confirmed.
(Consider endomycardial biopsy in case
of complications or signs of incomplete
recovery)
Prognostically relevant myocarditis unlikely
Clinical diagnosis of (peri)myocarditis
(despite normal CMR)
Non-eligible for competitive sports
and exercise of vigorous intensity for
3 months (despite good prognosis).
Recreational exercise of moderate
intensity is allowed on an individual
basis
Persisting symptoms
Complete recovery
(symptoms,
cardiological work-
up including
maximal exercise
test/CPET)
Exclusion of coronary artery disease
Complete recovery (symptoms, cardiological
work-up including maximal exercise
test/CPET). Advice on increased risk for
SCD in LGE+ (In uncertainty of risk of SCD,
CMR can be repeated after 6 months).
Incomplete recovery
Non-eligible for competitive sports
and exercise of vigorous intensity.
Restricted to low to moderate
intensity exercise. Reevaluation
every 3– 6 months.
Eligible for any exercise and
competitive sport depending
on risk for SCD (LGE)
Cardiological work-up: ECG, echocardiography, 24 h Holter ECG, inflammatory markers, cardiac biomarkers
Figure 3. Algorithm for sports and exercise eligibility in myocarditis.
SCD: sudden cardiac death; CMR: cardiac magnetic resonance imaging; CPET: cardio-pulmonary exercise testing; EF: left ventricular
ejection fraction; LGE: late gadolinium enhancement.
Halle et al. 7
MACE rate of 10.5% and mortality rate of 3.1% over
five years.
27
In patients with mildly impaired LV func-
tion, the presence of fibrosis also significantly increases
the risk for MACE and mortality.
27
However, clinically indicated recommendations are
not clear in those with completely normal LV function
with persistent LGE. Recent data from the ITAMY
registry indicate variability of LGE over six months
and an increased risk for cardiac events in LGE-
positive subjects.
35
Positive LGE may reflect post-
inflammatory scarring, but is also found in 12% of
asymptomatic athletes.
38
Until the pathophysiology,
differential diagnosis, and clinical significance of this
constellation is better understood, decision-making
will remain extremely difficult. However, from a current
perspective, eligibility for sports can mostly be recom-
mended, but only on an individual basis and close
follow-up examinations (Figure 3).
Overall, recommendations for eligibility for sports
should specify type and cardio-pulmonary intensity of
sports (e.g. marathon running vs golf), and also include
sports conditions at altitude or in water (e.g. climbing
or swimming) with high fatality risk during arrhyth-
mias and subsequent unconsciousness. An approach
of shared decision-making with well-informed athletes
is of utmost importance, as, from our experience, both
recreational and elite athletes continue their sports des-
pite restrictive advice from their attending medical pro-
fessional. Therefore, detailed documentation is also
mandatory for both forensic and legal reasons.
Exercise recommendations after recovery
from acute myocarditis
Before starting an exercise program, a CPET has to be
performed, which will yield maximal exercise capacity
as well as individual exercise intensity thresholds.
47
Initially, sessions are limited to regenerative intensity
levels (<50% VO
2max
), which will then be gradually
increased in duration and, if tolerated well, also in
intensity (50–75% VO
2max
). Dynamic resistance exer-
cise can also be included in this phase. Exercise tests
should be repeated after six and 12 weeks for assess-
ment of pathologies, and particularly before adaptation
of exercise of even higher intensity levels (>75%
VO
2max
). If maximal exercise is tolerated well and no
other pathologies – for example, impaired LV function
or arrhythmias are present – recommendation of full
eligibility can usually be given. In general, in recre-
ational as well as competitive athletes, a definition
and detailed prescription of mode, duration, as well
as definite exercise heart rate corridor is particularly
important, as these individuals often have a vastly dif-
ferent view and perception of training intensities or
optimal training schedule.
Preventative measures
For some of the above-mentioned microbial infections,
preventive measures are available in the form of vac-
cinations (Corynebacterium diphtheria, influenza virus,
tuberculosis (although less effective in the common
respiratory form)), general hygiene, and cautious con-
tact with animals and uncooked foods. Repellents and
appropriate clothing improve personal tick bite protec-
tion, particularly in athletes performing outdoor sports
and training (Lyme disease). Physicians caring for ath-
letes should frequently advise the athlete and coaches
against the use of illicit drugs. Moreover, lifestyle meas-
ures should be followed by athletes, including reduced
alcohol consumption, healthy food, regular sleep, and
avoidance of large groups of people with sufficient
recovery after travels, strenuous training sessions, and
competitions (Figure 1 and Table 1).
Recommendations for exercise training and compe-
tition in athletes with clinical symptoms of infection
are based on expert opinions only. In the presence
of common symptoms of upper airway and gastrointes-
tinal infections, particularly when accompanied by gen-
eral symptoms (e.g. fatigue), athletes should be very
cautious and significantly reduce exercise intensity
and prolong recovery periods after training sessions.
Optimally, endurance exercise should be stopped for a
minimum for 2–3 days when symptoms are present,
and may be fully resumed only after 3–4 days of com-
plete recovery. Exercise without cardio-pulmonary
strain, such as skill exercises, may be resumed earlier.
Athletes presenting with fever, general fatigue, periph-
eral muscle soreness, or even muscle pain are advised to
refrain from any exercise while symptoms persist. These
patients may resume exercise 5–7 days after symptoms
subside, but with reduced volume and intensity load.
48
Special counselling aspects in athletes
In acute myocarditis, the attending physician must
counsel the athlete and explain the generally prolonged
healing process, dangers of premature resumption of
exercise training, and potential of delayed disease
course, including potential lethal consequences. The
team physician and coach should be consulted and
advised on the risk associated with an athlete resuming
exercise too early. The diagnosis of myocarditis typic-
ally has a significant impact on an athlete’s career,
including cancellation of competitions, and potential
financial constraints. Therefore, early psychological
consultation may be advantageous. Team physicians
should take over the task to protect the athlete from
external psychological pressure of sponsors, coaches,
sports clubs, and league authorities. The collaboration
between a sports cardiologist and sports scientist is opti-
mal in defining an individually tailored training plan.
8European Journal of Preventive Cardiology 0(00)
Fortunately, most athletes with myocarditis undergo
complete recovery. Nonetheless, yearly cardiology con-
sultations remain important.
Clinical perspective and future research
Although (elite) athletes represent only a smaller group
within our society, the challenges for diagnosis, treat-
ment, and exercise recommendations are crucial for any
cardiologist in order to prevent an overall increased risk
of SCD. These also extend to recreational athletes – a
group that is constantly increasing in numbers.
There is a clear demand for extending knowledge of
myocarditis in recreational as well as elite athletes
through both animal and human studies, especially
for studies which employ current state-of-the-art scien-
tific methods. From a clinical perspective, the long-term
effects of exercise during the post-acute phase
(<3 months) and the importance of LGE is unresolved.
To answer this, we currently lack an international stan-
dardized registry on myocarditis in recreational and
elite athlete populations,
26
which would considerably
help to improve future decision-making on initiation
of general exercise and recommendations of eligibility
for recreational and competitive sports.
Author contribution
LB and MaH drafted the manuscript. MeH, MS, KE, and CT
critically revised the manuscript. All authors gave final
approval and agree to be accountable for all aspects of
work ensuring integrity and accuracy.
Acknowledgements
We thank Rhys Isaac Beaudry, College of Nursing and
Health Innovation, The University of Texas Arlington,
USA, and Lennard Halle, University of Freiburg, Germany,
for their critical comments.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
References
1. Harmon KG, Asif IM, Maleszewski JJ, et al. Incidence
and etiology of sudden cardiac arrest and death in high
school athletes in the United States. Mayo Clin Proc 2016;
91: 1493–1502.
2. Peretto G, Sala S, Rizzo S, et al. Arrhythmias in myocar-
ditis: state of the art. Heart Rhythm 2019; 16: 793–801.
3. Pelliccia A, Solberg EE, Papadakis M, et al.
Recommendations for participation in competitive and
leisure time sport in athletes with cardiomyopathies,
myocarditis, and pericarditis: position statement of the
Sport Cardiology Section of the European Association
of Preventive Cardiology (EAPC). Eur Heart J 2019;
40: 19–33.
4. Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and
disqualification recommendations for competitive ath-
letes with cardiovascular abnormalities: Task Force 3:
hypertrophic cardiomyopathy, arrhythmogenic right ven-
tricular cardiomyopathy and other cardiomyopathies,
and myocarditis: a scientific statement from the
American Heart Association and American College of
Cardiology. Circulation 2015; 132: e273–e280.
5. Pollack A, Kontorovich AR, Fuster V and Dec GW.
Viral myocarditis–diagnosis, treatment options, and cur-
rent controversies. Nat Rev Cardiol 2015; 12: 670–680.
6. Caforio AL, Pankuweit S, Arbustini E, et al. Current
state of knowledge on aetiology, diagnosis, management,
and therapy of myocarditis: a position statement of the
European Society of Cardiology Working Group on
Myocardial and Pericardial Diseases. Eur Heart J 2013;
34: 2636–2648, 2648a–2648d.
7. Maron BJ, Haas TS, Ahluwalia A, et al. Incidence of
cardiovascular sudden deaths in Minnesota high school
athletes. Heart Rhythm 2013; 10: 374–377.
8. Finocchiaro G, Papadakis M, Robertus JL, et al.
Etiology of sudden death in sports: insights from a
United Kingdom regional registry. J Am Coll Cardiol
2016; 67: 2108–2115.
9. Nieman DC. Marathon training and immune function.
Sports Med 2007; 37: 412–415.
10. Kiel RJ, Smith FE, Chason J, et al. Coxsackievirus B3
myocarditis in C3H/HeJ mice: description of an inbred
model and the effect of exercise on virulence. Eur J
Epidemiol 1989; 5: 348–350.
11. Gatmaitan BG, Chason JL and Lerner AM.
Augmentation of the virulence of murine coxsackie-
virus B-3 myocardiopathy by exercise. J Exp Med 1970;
131: 1121–1136.
12. Ilback NG, Fohlman J and Friman G. Exercise in cox-
sackie B3 myocarditis: effects on heart lymphocyte sub-
populations and the inflammatory reaction. Am Heart J
1989; 117: 1298–1302.
13. Cabinian AE, Kiel RJ, Smith F, et al. Modification of
exercise-aggravated coxsackievirus B3 murine myocardi-
tis by T lymphocyte suppression in an inbred model.
J Lab Clin Med 1990; 115: 454–462.
14. Kindermann I, Barth C, Mahfoud F, et al. Update on
myocarditis. J Am Coll Cardiol 2012; 59: 779–792.
15. Tschope C, Bock CT, Kasner M, et al. High prevalence of
cardiac parvovirus B19 infection in patients with isolated
left ventricular diastolic dysfunction. Circulation 2005;
111: 879–886.
16. Maraj S, Figueredo VM and Lynn Morris D. Cocaine
and the heart. Clin Cardiol 2010; 33: 264–269.
17. La Gerche A and Brosnan MJ. Cardiovascular effects
of performance-enhancing drugs. Circulation 2017; 135:
89–99.
Halle et al. 9
18. Montisci M, El Mazloum R, Cecchetto G, et al. Anabolic
androgenic steroids abuse and cardiac death in athletes:
morphological and toxicological findings in four fatal
cases. Forensic Sci Int 2012; 217: e13–e18.
19. Maron BJ, Levine BD, Washington RL, et al.
Eligibility and disqualification recommendations for
competitive athletes with cardiovascular abnormalities:
Task Force 2: preparticipation screening for cardiovascu-
lar disease in competitive athletes: a scientific statement
from the American Heart Association and American
College of Cardiology. J Am Coll Cardiol 2015; 66:
2356–2361.
20. Sharma S, Drezner JA, Baggish A, et al. International
recommendations for electrocardiographic interpretation
in athletes. Eur Heart J 2018; 39: 1466–1480.
21. Corrado D, Drezner JA, D’Ascenzi F, et al. How to
evaluate premature ventricular beats in the athlete: crit-
ical review and proposal of a diagnostic algorithm. Brit J
Sport Med. Epub ahead of print 3 September 2019. DOI:
10.1136/bjsports-2018-100529.
22. Scherr J, Braun S, Schuster T, et al. 72-h kinetics of high-
sensitive troponin T and inflammatory markers after
marathon. Med Sci Sports Exerc 2011; 43: 1819–1827.
23. Kasner M, Aleksandrov A, Escher F, et al.
Multimodality imaging approach in the diagnosis of
chronic myocarditis with preserved left ventricular ejec-
tion fraction (MCpEF): the role of 2D speckle-tracking
echocardiography. Int J Cardiol 2017; 243: 374–378.
24. Pressler A, Haller B, Scherr J, et al. Association of body
composition and left ventricular dimensions in elite ath-
letes. Eur J Prev Cardiol 2012; 19: 1194–1204.
25. Ferreira VM, Schulz-Menger J, Holmvang G, et al.
Cardiovascular magnetic resonance in nonischemic myo-
cardial inflammation: expert recommendations. JAm
Coll Cardiol 2018; 72: 3158–3176.
26. Eichhorn C, Biere L, Schnell F, et al. Myocarditis in ath-
letes is a challenge: diagnosis, risk stratification, and uncer-
tainties. JACC Cardiovasc Imaging 2020; 13: 494–507.
27. Grani C, Eichhorn C, Biere L, et al. Prognostic value of
cardiac magnetic resonance tissue characterization in risk
stratifying patients with suspected myocarditis. J Am Coll
Cardiol 2017; 70: 1964–1976.
28. O’Connor MJ. Imaging the itis: endocarditis, myocardi-
tis, and pericarditis. Curr Opin Cardiol 2019; 34: 57–64.
29. Grun S, Schumm J, Greulich S, et al. Long-term follow-
up of biopsy-proven viral myocarditis: predictors of mor-
tality and incomplete recovery. J Am Coll Cardiol 2012;
59: 1604–1615.
30. Grani C, Biere L, Eichhorn C, et al. Incremental value of
extracellular volume assessment by cardiovascular mag-
netic resonance imaging in risk stratifying patients with
suspected myocarditis. Int J Cardiovasc Imaging 2019; 35:
1067–1078.
31. Grani C, Eichhorn C, Biere L, et al. Comparison of myo-
cardial fibrosis quantification methods by cardiovascular
magnetic resonance imaging for risk stratification of
patients with suspected myocarditis. J Cardiovasc Magn
Reson 2019; 21: 14.
32. Bohnen S, Radunski UK, Lund GK, et al. Tissue
characterization by T1 and T2 mapping cardiovascular
magnetic resonance imaging to monitor myocardial
inflammation in healing myocarditis. Eur Heart J
Cardiovasc Imaging 2017; 18: 744–751.
33. Mewton N, Dernis A, Bresson D, et al. Myocardial
biomarkers and delayed enhanced cardiac magnetic res-
onance relationship in clinically suspected myocarditis
and insight on clinical outcome. J Cardiovasc Med
(Hagerstown) 2015; 16: 696–703.
34. Schumm J, Greulich S, Wagner A, et al. Cardiovascular
magnetic resonance risk stratification in patients with
clinically suspected myocarditis. J Cardiovasc Magn
Reson 2014; 16: 14.
35. Aquaro GD, Ghebru Habtemicael Y, Camastra G, et al.
Prognostic value of repeating cardiac magnetic resonance
in patients with acute myocarditis. J Am Coll Cardiol
2019; 74: 2439–2448.
36. Zorzi A, Perazzolo Marra M, Rigato I, et al.
Nonischemic left ventricular scar as a substrate of
life-threatening ventricular arrhythmias and sudden car-
diac death in competitive athletes. Circ Arrhythm
Electrophysiol 2016; 9: e004229.
37. Aquaro GD, Perfetti M, Camastra G, et al. Cardiac MR
with late gadolinium enhancement in acute myocarditis
with preserved systolic function: ITAMY Study. JAm
Coll Cardiol 2017; 70: 1977–1987.
38. Breuckmann F, Mohlenkamp S, Nassenstein K, et al.
Myocardial late gadolinium enhancement: prevalence,
pattern, and prognostic relevance in marathon runners.
Radiology 2009; 251: 50–57.
39. Wilson M, O’Hanlon R, Prasad S, et al. Diverse patterns
of myocardial fibrosis in lifelong, veteran endurance ath-
letes. J Appl Physiol 2011; 110: 1622–1626.
40. van de Schoor FR, Aengevaeren VL, Hopman MT, et al.
Myocardial fibrosis in athletes. Mayo Clin Proc 2016; 91:
1617–1631.
41. Lurz P, Luecke C, Eitel I, et al. Comprehensive cardiac
magnetic resonance imaging in patients with suspected
myocarditis: the MyoRacer-Trial. J Am Coll Cardiol
2016; 67: 1800–1811.
42. Meeusen R, Duclos M, Foster C, et al. Prevention, diag-
nosis, and treatment of the overtraining syndrome: joint
consensus statement of the European College of Sport
Science and the American College of Sports Medicine.
Med Sci Sports Exerc 2013; 45: 186–205.
43. Tschope C, Cooper LT, Torre-Amione G, et al.
Management of myocarditis-related cardiomyopathy in
adults. Circ Res 2019; 124: 1568–1583.
44. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC
guidelines for the diagnosis and treatment of acute and
chronic heart failure: the Task Force for the Diagnosis
and Treatment of Acute and Chronic Heart Failure of the
European Society of Cardiology (ESC). Developed with
10 European Journal of Preventive Cardiology 0(00)
the special contribution of the Heart Failure Association
(HFA) of the ESC. Eur J Heart Fail 2016; 18: 891–975.
45. Tschope C, Elsanhoury A, Schlieker S, et al.
Immunosuppression in inflammatory cardiomyopathy
and parvovirus B19 persistence. Eur J Heart Fail 2019;
21: 1468–1469.
46. Schindler MJ and Adams V and Halle M. Exercise in
heart failure-what is the optimal dose to improve patho-
physiology and exercise capacity? Curr Heart Fail Rep
2019; 16: 98–107.
47. Guazzi M, Adams V, Conraads V, et al. EACPR/AHA
Scientific Statement. Clinical recommendations for
cardiopulmonary exercise testing data assessment in spe-
cific patient populations. Circulation 2012; 126:
2261–2274.
48. Scharhag J and Meyer T. Return to play after acute infec-
tious disease in football players. J Sports Sci 2014; 32:
1237–1242.
Halle et al. 11
