Myocardial Inflammation Clinical Trial
Official title:
Cardiac Magnetic Resonance Evaluation of Myocardial Inflammation Persistence After Acute Myocarditis: Prognostic Relevance
Patients with acute myocarditis (AM) usually experience spontaneous healing, but a
considerable percentage of them evolve towards chronic long-term cardiac impairment. The
evolution towards dilated cardiomyopathy (DCM) occurs in a subtle manner, frequently after an
initial recover that mimics complete healing. Differences in the course of the disease may
reflect the course of underlying myocardial inflammation related to viral clearance or
persistence and to the following autoimmune response.
Cardiac magnetic resonance (CMR) mapping parameters have been developed for the
quantification of edema and necrosis, showing high diagnostic accuracy. No mapping parameter
has been developed for the assessment of the third Lake Louise criteria, namely the
hyperemia, and, furthermore, their prognostic role is not completely understood.
The study hypothesis is that the early-enhanced T1 mapping parameter may have great
diagnostic accuracy for myocarditis, and that a short-term monitoring with a complete CMR
protocol at 2 month after symptoms onset may identify the subgroup of patients at high risk
of progression towards DCM.
The results of this study will help to significantly improve diagnostic performances of CMR
and may help to manage patients with AM.
Background and Significance:
In patients with acute myocarditis (AM), spontaneous improvement can be observed in the
majority of cases, but progression towards dilated cardiomyopathy (DCM) is a not rare outcome
(around 20% of patients) (Feldmann N Engl J Med 2000;343:1388-98). Differences in the course
of the disease may reflect the course of the underlying viral infection. In a large series of
patients with AM submitted to two endo-myocardial biopsies (EMBs) in few months, Kuhl
demonstrated that viral clearance was associated with spontaneous ejection fraction (EF)
improvement, while EF did not improve or even deteriorated in patients with viral and
myocardial inflammation persistence (Kühl Circulation 2005;111:887-93. Kühl Circulation
2005;112:1965-70). However, repeated EMBs cannot be proposed in the clinical routine and,
hence, non-invasive detection of the subgroup of patients with inflammation persistence
should have important implications. Today, cardiac magnetic resonance (CMR) is recognized as
an accurate non-invasive imaging tool to diagnose acute myocarditis, because of its ability
to detect myocardial inflammation and necrosis (Friedrich J Am Coll Cardiol 2009;53:1475-87).
The introduction of mapping techniques has significantly improved CMR sensitivity, allowing
to detect both focal and diffuse involvement, with a substantial benefit in the convalescent
phase where conventional Lake Louise criteria often fail.
However, no technical development has been performed for the evaluation of Early Gadolinium
Enhancement (EGE), which continues to be assessed on T1-w images, being the less robust Lake
Louise criteria and eliminated from the updated Lake Louise criteria [Ferreira J Am Coll
Cardiol 2018;72(24):3158-76.].
Therefore, there are two major clinical needs: (a) the first being the improvement in
diagnosis fulfilling the lack in technical advancement in the setting of EGE evaluation, (b)
the second being risk-stratification and prediction of prognosis. The study hypothesis is
that the development of a quantitative method based on T1 mapping for the assessment of EGE
may be highly sensitive and specific for the diagnosis of myocarditis. Then, the assessment
of early changes in CMR parameters at a short-term CMR study (2 months after symptoms onset)
may have great value in outcome prediction.
Preliminary data: A previous study performed on patients with chronic inflammatory
cardiomyopathy demonstrated that the positivity of CMR parameters of necrosis (LGE) and
inflammation (oedema) is significantly higher in patients with an active inflammation at EMB,
compared to patients with borderline histological criteria (De Cobelli 2006 JACC;47:1649-54).
These data suggest the possibility to detect with CMR the persistence of subtle myocardial
inflammation after the acute phase in patients with myocarditis.
Moreover, Wagner and Colleagues demonstrated, in a small group of patients, a correlation
between CMR evidence of myocardial hyperaemia persistence 4 weeks after the onset of acute
myocarditis and negative left ventricular (LV) remodelling 30 months later (Wagner A 2003
MAGMA;16:17-20).
Materials and Methods:
This is a prospective multicentre cohort study. 80 patients with diagnosis of acute
myocarditis (AM) will be enrolled.
All patients admitted to Hospital with suspect of AM will be submitted to:
collection of detailed anamnesis and physical examination, 12-lead ECG, laboratory exams,
transthoracic echocardiography, coronary catheterization or coronary computed tomography (CT)
angiography when an ischemic cause of symptoms need to be excluded and CMR imaging within 3-5
days.
CMR protocol will include Lake-Louise criteria, parametric mappings (native T1, T2 mapping
and ECV), with an additional early-enhanced T1 mapping acquired 2 minutes after gadolinium
injection.
All patients with clinically or EMB confirmed diagnosis of AM will be enrolled and will
undergo a second CMR study 2 month later.
All patients will undergo a clinical/instrumental follow-up including: CMR assessment of LV
ejection fraction and end-diastolic volume after at least 1 year from diagnosis; registration
of all-cause mortality, cardiac death and aborted cardiac sudden death in patients with
implantable cardioverter-defibrillator (ICD).
Impact and Translational Implications:
Myocarditis is characterized by significant heterogeneity of long-term evolution. CMR could
play a key role in the non-invasive and early identification of patients with persistent
myocardial inflammation, at high risk to evolve towards an irreversible post-myocarditis
heart failure. Thus, CMR may help to design tailored management of patients. In this
perspective, invasive characterization of damage mechanism and aetiology might be reserved to
patients with CMR evidence of inflammation persistence.
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