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Myocarditis AcuteMIAMINCT03525639

CMR Evaluation of Myocardial Inflammation Persistence After Acute Myocarditis: Prognostic Relevance

A study testing Cardiac Magnetic Resonance in people with Myocarditis Acute and Myocardial Inflammation, run by Antonio Esposito at 3 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Myocarditis Acute, Myocardial Inflammation
What is being tested?
Cardiac Magnetic Resonance
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
3 sitesItaly
Study dates
6 Dec 2016to 20 Feb 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Presence of at least 1 of the subsequent clinical features [12]:
  • Acute chest pain (pericarditic, or pseudo-ischaemic)
  • New-onset dyspnoea at rest or during exercise
  • Fatigue with or without left/right heart failure signs
  • Palpitation or unexplained arrhythmia symptoms or syncope or aborted sudden cardiac death
  • Unexplained cardiogenic shock
Show all 11Show fewer
  • Associated with at least 1 of the subsequent diagnostic criteria [12]:
  • Newly abnormal 12 lead ECG and/or Holter and/or stress testing, any of the following: I to III degree atrioventricular block, or bundle branch block, ST/T wave change, sinus arrest, ventricular tachycardia or fibrillation and asystole, atrial fibrillation, reduced R wave height, intraventricular conduction delay, abnormal Q waves, low voltage, frequent premature beats, supraventricular tachycardia
  • Myocardial injury markers (elevated troponin T/Troponin I)
  • New, otherwise unexplained left ventricular (LV) and/or right ventricular (RV) functional and/or structural abnormalities on cardiac imaging (echo/angio/CMR) compatible with acute myocarditis and excluding other diseases
  • Signed informed consent

Who cannot join

  • History of cardiomyopathies
  • Coronary artery disease (coronary catheterization or CT angiography will be performed when coronary artery disease need to be excluded in consideration of signs and symptoms)
  • ICD or pacemaker
  • Inability to hold breath or to lay down for 45 min
  • Claustrophobia
  • Recent history of alimentary/alcoholic/respiratory intoxication
Show all 10Show fewer
  • CMR diagnostic criteria suggestive of other cardiac disease explaining signs and symptoms (e.g. myocardial infarction with patent coronary arteries, tako-tsubo syndrome)
  • Risk for nephrogenic systemic fibrosis (estimated glomerular filtration rate < 30 mL/min/1.73 m2)
  • History of allergic reaction to MR contrast media
  • Pregnancy or breast-feeding

Trial locations and contacts

3 sites in 1 country.

Italy3 sites

  • IRCCS San Raffaele

    Milan, 20132

  • Policlinico Umberto I

    Roma

  • AOU Città della Salute e della Scienza

    Torino

Other trials in Italy

About this study

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.

Read more

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.

Read the detailed description

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.

Being tested
Cardiac Magnetic Resonance
Keywords
Cardiac Magnetic Resonance, Acute Myocarditis, Myocardial Inflammation
Medical subject headings
Myocarditis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cardiac Magnetic ResonanceDiagnostic test

    Additional CMR study 2 month after the initial diagnosis of acute myocarditis to assess myocardial inflammation persistence (2-month-CMR).

Study groups in NCT03525639
Study groupRoleWhat they receive
Patients with Acute MyocarditisExperimentalPatients undergoing Cardiac Magnetic Resonance at baseline, 2 month, 1 year.
Receives: Diagnostic Test: Cardiac Magnetic Resonance

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Improvement in CMR diagnosis with early enhanced T1 mapping and early changes in CMR parameters reflecting inflammation activity

    T2 ratio; LGE (Late Gadolinium Enhancement); native T1 relaxation time; T2 relaxation time; extracellular volume fraction (ECV); early enhanced T1 relaxation time; baseline; 2 month; delta (2 month - baseline).

    Measured: Baseline; 2 month

  2. MACE and left ventricular remodelling

    Major adverse cardiac events (MACE): cardiac death; aborted sudden cardiac death; all-cause mortality.

    Left ventricular end-diastolic volume (LV EDV); left ventricular ejection fraction (LVEF).

    Measured: Inclusion; 2 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2018
  2. Study start6 Dec 2016
  3. Primary completion31 Dec 2020
  4. Study completion20 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03525639
Sponsor's protocol ID
MIAMI GR-2013-02356832
Acronym
MIAMI
Status last verified
Apr 2021
First submitted
3 May 2018
Last updated
1 May 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Youn JC, Shim HS, Lee JS, Ji AY, Oh J, Hong N, Lee HS, Park S, Lee SH, Choi D, Chung N, Kang SM. Detailed pathologic evaluation on endomyocardial biopsy provides long-term prognostic information in patients with acute myocarditis. Cardiovasc Pathol. 2014 May-Jun;23(3):139-44. doi: 10.1016/j.carpath.2014.01.004. Epub 2014 Jan 17.

    PubMed 24529879

  • Anzini M, Merlo M, Sabbadini G, Barbati G, Finocchiaro G, Pinamonti B, Salvi A, Perkan A, Di Lenarda A, Bussani R, Bartunek J, Sinagra G. Long-term evolution and prognostic stratification of biopsy-proven active myocarditis. Circulation. 2013 Nov 26;128(22):2384-94. doi: 10.1161/CIRCULATIONAHA.113.003092. Epub 2013 Oct 1.

    PubMed 24084750

  • Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet. 2012 Feb 25;379(9817):738-47. doi: 10.1016/S0140-6736(11)60648-X. Epub 2011 Dec 18.

    PubMed 22185868

  • Kuhl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W, Kandolf R, Schultheiss HP. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with "idiopathic" left ventricular dysfunction. Circulation. 2005 Feb 22;111(7):887-93. doi: 10.1161/01.CIR.0000155616.07901.35. Epub 2005 Feb 7.

    PubMed 15699250

  • Kuhl U, Pauschinger M, Seeberg B, Lassner D, Noutsias M, Poller W, Schultheiss HP. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation. 2005 Sep 27;112(13):1965-70. doi: 10.1161/CIRCULATIONAHA.105.548156. Epub 2005 Sep 19.

    PubMed 16172268

  • Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, White JA, Abdel-Aty H, Gutberlet M, Prasad S, Aletras A, Laissy JP, Paterson I, Filipchuk NG, Kumar A, Pauschinger M, Liu P; International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009 Apr 28;53(17):1475-87. doi: 10.1016/j.jacc.2009.02.007.

    PubMed 19389557

  • Mahrholdt H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, Vogelsberg H, Fritz P, Dippon J, Bock CT, Klingel K, Kandolf R, Sechtem U. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation. 2006 Oct 10;114(15):1581-90. doi: 10.1161/CIRCULATIONAHA.105.606509. Epub 2006 Oct 2.

    PubMed 17015795

  • Natale L, De Vita A, Baldari C, Meduri A, Pieroni M, Lombardo A, Crea F, Bonomo L. Correlation between clinical presentation and delayed-enhancement MRI pattern in myocarditis. Radiol Med. 2012 Dec;117(8):1309-19. doi: 10.1007/s11547-012-0790-x. Epub 2012 Feb 10. English, Italian.

    PubMed 22327917

  • Grun S, Schumm J, Greulich S, Wagner A, Schneider S, Bruder O, Kispert EM, Hill S, Ong P, Klingel K, Kandolf R, Sechtem U, Mahrholdt H. Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery. J Am Coll Cardiol. 2012 May 1;59(18):1604-15. doi: 10.1016/j.jacc.2012.01.007. Epub 2012 Feb 22.

    PubMed 22365425

  • Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Helio T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM; European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. 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 Sep;34(33):2636-48, 2648a-2648d. doi: 10.1093/eurheartj/eht210. Epub 2013 Jul 3.

    PubMed 23824828

  • De Cobelli F, Pieroni M, Esposito A, Chimenti C, Belloni E, Mellone R, Canu T, Perseghin G, Gaudio C, Maseri A, Frustaci A, Del Maschio A. Delayed gadolinium-enhanced cardiac magnetic resonance in patients with chronic myocarditis presenting with heart failure or recurrent arrhythmias. J Am Coll Cardiol. 2006 Apr 18;47(8):1649-54. doi: 10.1016/j.jacc.2005.11.067. Epub 2006 Mar 29.

    PubMed 16631005

  • Wagner A, Schulz-Menger J, Dietz R, Friedrich MG. Long-term follow-up of patients paragraph sign with acute myocarditis by magnetic paragraph sign resonance imaging. MAGMA. 2003 Feb;16(1):17-20. doi: 10.1007/s10334-003-0007-7.

    PubMed 12695882

  • Francone M, Chimenti C, Galea N, Scopelliti F, Verardo R, Galea R, Carbone I, Catalano C, Fedele F, Frustaci A. CMR sensitivity varies with clinical presentation and extent of cell necrosis in biopsy-proven acute myocarditis. JACC Cardiovasc Imaging. 2014 Mar;7(3):254-63. doi: 10.1016/j.jcmg.2013.10.011. Epub 2014 Feb 19.

    PubMed 24560214

  • Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. Eur Heart J. 2009 Aug;30(16):1995-2002. doi: 10.1093/eurheartj/ehp249. Epub 2009 Jun 25.

    PubMed 19556262

  • Chimenti C, Kajstura J, Torella D, Urbanek K, Heleniak H, Colussi C, Di Meglio F, Nadal-Ginard B, Frustaci A, Leri A, Maseri A, Anversa P. Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res. 2003 Oct 3;93(7):604-13. doi: 10.1161/01.RES.0000093985.76901.AF. Epub 2003 Sep 4.

    PubMed 12958145

Questions about this trial

What is this clinical trial studying?

A study testing Cardiac Magnetic Resonance in people with Myocarditis Acute and Myocardial Inflammation, run by Antonio Esposito at 3 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Improvement in CMR diagnosis with early enhanced T1 mapping and early changes in CMR parameters reflecting inflammation activity (time frame: Baseline; 2 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03525639, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2025.

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