Recurrent Acute Myocarditis Registry

Cardiomyopathy Clinical Trial

— RAM  

Official title:

Recurrent Acute Myocarditis : Characteristics, Etiology, Prognosis and Genetic Basis.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04589156
• Other study ID #: Rythmo20200818
• Status: Recruiting
• Start date: January 1, 2018
• Est. completion date: January 1, 2022

Study information

• Verified date: October 2020
• Source: University Hospital, Caen
• Contact: Pierre Ollitrault, MD, MSc
• Phone: 0231064418
• Email: ollitrault-p[@]chu-caen.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The association between myocardial inflammation (clinically represented by acute myocarditis episodes) and the later development of an arrhythmogenic cardiomyopathy is widely elusive.

Description:

Acute myocarditis (AM) is an inflammatory disease of the myocardium caused by different infectious and non-infectious triggers. It is a major cause of sudden cardiac death, with also long-term adverse outcomes in survivors. The incidence and predictive factors of recurrent AM (RAM) are unknown. Arrhythmogenic cardiomyopathy (ACM) is a genetically-determined or acquired arrhythmogenic disorder of the myocardium. With an incidence of 1/5000, genetic ACM is the consequence of pathogenic variants in genes encoding for desmosomal and cytoskeleton proteins. Originally described as a right ventricular disease (ARVC), genetic ACM is increasingly recognized as a left (ALVC) or biventricular entity. Genetic ACM may manifest with various clinical presentations, with a predisposition to acute and chronic heart failure, ventricular arrhythmias and sudden cardiac death. Pathophysiology of genetic ACM at early stages remain widely elusive. Myocardial inflammation has been consistently reported in patients with genetic ACM, but the exact nature of their association is a matter of debate. The temporal association between RAM episodes and the later diagnosis of genetic ACM is speculative, and it has been hypothesized recently that RAM episodes might reflect early active phases in the development of a genetic ACM. The investigators aim to study the temporal association between RAM episodes and the later diagnosis of an ACM. Consecutive patients with at least two episodes of AM and referred to a tertiary university referral center (pop. 1.500.000 inhabitants) for clinical expertise, follow-up and etiological work-out were prospectively included in this registry.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 1, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria: patients with at least two episodes of acute myocarditis as defined by the European Society of Cardiology diagnostic criteria.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Myocarditis

Locations

Country	Name	City	State
France	Caen University Hospital	Caen	Normandy

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Caen

Country where clinical trial is conducted

France, 

References & Publications (16)

Ader F, Surget E, Charron P, Redheuil A, Zouaghi A, Maltret A, Marijon E, Denjoy I, Hermida A, Fressart V, Gandjbakhch E. Inherited Cardiomyopathies Revealed by Clinically Suspected Myocarditis: Highlights From Genetic Testing. Circ Genom Precis Med. 2020 Aug;13(4):e002744. doi: 10.1161/CIRCGEN.119.002744. Epub 2020 Jun 10. — View Citation

Asimaki A, Tandri H, Duffy ER, Winterfield JR, Mackey-Bojack S, Picken MM, Cooper LT, Wilber DJ, Marcus FI, Basso C, Thiene G, Tsatsopoulou A, Protonotarios N, Stevenson WG, McKenna WJ, Gautam S, Remick DG, Calkins H, Saffitz JE. Altered desmosomal proteins in granulomatous myocarditis and potential pathogenic links to arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol. 2011 Oct;4(5):743-52. doi: 10.1161/CIRCEP.111.964890. Epub 2011 Aug 22. — View Citation

Bauce B, Basso C, Rampazzo A, Beffagna G, Daliento L, Frigo G, Malacrida S, Settimo L, Danieli G, Thiene G, Nava A. Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations. Eur Heart J. 2005 Aug;26(16):1666-75. Epub 2005 Jun 7. — View Citation

Belkaya S, Kontorovich AR, Byun M, Mulero-Navarro S, Bajolle F, Cobat A, Josowitz R, Itan Y, Quint R, Lorenzo L, Boucherit S, Stoven C, Di Filippo S, Abel L, Zhang SY, Bonnet D, Gelb BD, Casanova JL. Autosomal Recessive Cardiomyopathy Presenting as Acute Myocarditis. J Am Coll Cardiol. 2017 Apr 4;69(13):1653-1665. doi: 10.1016/j.jacc.2017.01.043. — View Citation

Bowles NE, Ni J, Marcus F, Towbin JA. The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2002 Mar 6;39(5):892-5. — View Citation

Brown EE, McMilllan KN, Halushka MK, Ravekes WJ, Knight M, Crosson JE, Judge DP, Murphy AM. Genetic aetiologies should be considered in paediatric cases of acute heart failure presumed to be myocarditis. Cardiol Young. 2019 Jul;29(7):917-921. doi: 10.1017/S1047951119001124. Epub 2019 Jun 14. — View Citation

Burke AP, Farb A, Tashko G, Virmani R. Arrhythmogenic right ventricular cardiomyopathy and fatty replacement of the right ventricular myocardium: are they different diseases? Circulation. 1998 Apr 28;97(16):1571-80. — View Citation

Caforio ALP, Re F, Avella A, Marcolongo R, Baratta P, Seguso M, Gallo N, Plebani M, Izquierdo-Bajo A, Cheng CY, Syrris P, Elliott PM, d'Amati G, Thiene G, Basso C, Gregori D, Iliceto S, Zachara E. Evidence From Family Studies for Autoimmunity in Arrhythmogenic Right Ventricular Cardiomyopathy: Associations of Circulating Anti-Heart and Anti-Intercalated Disk Autoantibodies With Disease Severity and Family History. Circulation. 2020 Apr 14;141(15):1238-1248. doi: 10.1161/CIRCULATIONAHA.119.043931. Epub 2020 Mar 2. — View Citation

Chimenti C, Pieroni M, Maseri A, Frustaci A. Histologic findings in patients with clinical and instrumental diagnosis of sporadic arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol. 2004 Jun 16;43(12):2305-13. — View Citation

Lopez-Ayala JM, Pastor-Quirante F, Gonzalez-Carrillo J, Lopez-Cuenca D, Sanchez-Munoz JJ, Oliva-Sandoval MJ, Gimeno JR. Genetics of myocarditis in arrhythmogenic right ventricular dysplasia. Heart Rhythm. 2015 Apr;12(4):766-73. doi: 10.1016/j.hrthm.2015.01.001. Epub 2015 Jan 20. — View Citation

Martins D, Ovaert C, Khraiche D, Boddaert N, Bonnet D, Raimondi F. Myocardial inflammation detected by cardiac MRI in Arrhythmogenic right ventricular cardiomyopathy: A paediatric case series. Int J Cardiol. 2018 Nov 15;271:81-86. doi: 10.1016/j.ijcard.2018.05.116. Epub 2018 May 31. — View Citation

Peretto G, Sala S, Rizzo S, Palmisano A, Esposito A, De Cobelli F, Campochiaro C, De Luca G, Foppoli L, Dagna L, Thiene G, Basso C, Della Bella P. Ventricular Arrhythmias in Myocarditis: Characterization and Relationships With Myocardial Inflammation. J Am Coll Cardiol. 2020 Mar 10;75(9):1046-1057. doi: 10.1016/j.jacc.2020.01.036. — View Citation

Piriou N, Marteau L, Kyndt F, Serfaty JM, Toquet C, Le Gloan L, Warin-Fresse K, Guijarro D, Le Tourneau T, Conan E, Thollet A, Probst V, Trochu JN. Familial screening in case of acute myocarditis reveals inherited arrhythmogenic left ventricular cardiomyopathies. ESC Heart Fail. 2020 Aug;7(4):1520-1533. doi: 10.1002/ehf2.12686. Epub 2020 May 1. — View Citation

Protonotarios A, Wicks E, Ashworth M, Stephenson E, Guttmann O, Savvatis K, Sekhri N, Mohiddin SA, Syrris P, Menezes L, Elliott P. Prevalence of (18)F-fluorodeoxyglucose positron emission tomography abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy. Int J Cardiol. 2019 Jun 1;284:99-104. doi: 10.1016/j.ijcard.2018.10.083. Epub 2018 Oct 26. — View Citation

Smith ED, Lakdawala NK, Papoutsidakis N, Aubert G, Mazzanti A, McCanta AC, Agarwal PP, Arscott P, Dellefave-Castillo LM, Vorovich EE, Nutakki K, Wilsbacher LD, Priori SG, Jacoby DL, McNally EM, Helms AS. Desmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct From Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation. 2020 Jun 9;141(23):1872-1884. doi: 10.1161/CIRCULATIONAHA.119.044934. Epub 2020 May 6. — View Citation

Tanawuttiwat T, Sager SJ, Hare JM, Myerburg RJ. Myocarditis and ARVC/D: variants or mimics? Heart Rhythm. 2013 Oct;10(10):1544-8. doi: 10.1016/j.hrthm.2013.06.008. Epub 2013 Jun 14. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained ventricular arrhythmia	Any ventricular arrhythmia (VT/VF) : sustained (lasting more than 30 seconds); symptomatic or not (including sudden cardiac arrest); induced or not (including during stress ECG, pharmacological challenge or electrophysiological study)	0 - 1 year after last acute myocarditis episode
Primary	Genetic mutation	Any genetic mutation (cardiomyopathy panel)	0 - 1 year after last acute myocarditis episode
Secondary	Myocardial substrate characterization	Cardiac magnetic resonance imaging (left and right ventricular ejection fractions, volumes, late gadolinium enhancement)	0 - 1 year after last acute myocarditis episode
Secondary	Nonsustained ventricular arrhythmia	Any ventricular arrhythmia (VT/VF) : nonsustained (lasting less than 30 seconds); symptomatic or not; induced or not (including during stress ECG, pharmacological challenge or electrophysiological study)	0 - 1 year after last acute myocarditis episode