**7. References**

Andréoletti L, Ventéo L, Douche-Aourik F, et al. Active Coxsackieviral B infection is associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial infarction. J Am Coll Cardiol 2007;50:2207-14.

No specific trial or data from single-center studies on the treatment of myocarditis presenting with ventricular arrhythmias are currently available in literature. In patients with acute myocarditis, therapy for arrhythmias is essentially supportive, since arrhythmias usually resolve after the acute phase of the disease, which can last several weeks, together with the resoluton of the inflammatory process. Even in chronic myocarditis, management of ventricular arrhythmias is currently confined to antiarrhythmic drug therapy, with limited efficacy, and to implantable cardioverter-defibrillator for higher-risk patients, including those with hemodynamically unstable ventricular tachycardias (Zipes et al., 2006) and those with aborted sudden death. Radiofrequency catheter ablation has been demonstrated to be effective in reducing ventricular tachycardia occurrence in patients with Chagas cardiomyopathy and sarcoidosis. Regarding ventricular arrhythmias in patients with lymphocytic myocarditis, isolated reports suggest that RFCA may be effective, (Chauhan et al., 2008; Hama et al. 2009; Kettering et al., 2009; Zeppenfeld et al., 2007) but its safety and long-term efficacy in this setting is unclear. In our Institution we documented the safety and efficacy of RFCA in a series of consecutive patients with chronic active myocarditis presenting with drug-refractory ventricular tachycardias. We enrolled 20 pts with biopsy-proven myocarditis and drug-refractory ventricular tachycardia including 5 pts presenting with electrical storm. All patients underwent endocardial RFCA with an irrigation catheter, using contact electroanatomical mapping. Recurrence of sustained ventricular tachycardia after endocardial RFCA was treated with additional epicardial RFCA. Endocardial RFCA was acutely successful in 14 pts (70%), while in the remaining 6 pts (30%) clinical ventricular tachycardia was successfully ablated by epicardial RFCA thus demonstrating that in patients with myocarditis, RFCA of drug-refractory ventricular tachycardia is feasible, safe and effective and that epicardial RFCA should be considered as an important therapeutic option to increase success rate (Pieroni and colleagues in press).

Myocarditis represents a frequent but often underestimated cause of life-threatening ventricular arrhyhmias and sudden arrhythmic death and therefore should be always suspected in these clinical settings. The recognition of myocarditis as the cuase of ventricular arrhythmias may have dramatic implications on treatment and prognosis. Imaging techniques such as CMR have improved our ability to recognize myocardial inflammatory damage, and increased the awareness of the disease among physicians. Nevertheless EMB still represents the gold standard for the diagnosis of myocarditis as offers a immunohistological and virological characterization of thr inflammatoty process that may influence the treatment. Electroanatomic mapping-guided EMB represents a new important technique that allows increasing diagnostic sensitivity and minimizing the sampling error in patients with myocarditis presenting with arrhythmias. In the next future 3D-EAM-guide EMB will also represent an important research tool in the study of

Andréoletti L, Ventéo L, Douche-Aourik F, et al. Active Coxsackieviral B infection is

associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial infarction. J Am Coll Cardiol 2007;50:2207-14.

channellopathies and other genetically determined arrhythmic syndromes.

**6. Conclusion** 

**7. References** 


Myocarditis Presenting with Ventricular Arrhythmias:

Rhythm 2006;3:924 –9.

Circulation 2003; 107: 2793-2798.

Role of Electroanatomical Mapping-Guided Endomyocardial Biopsy in Differential Diagnosis 385

Kishimoto C, Matsumori A, Kawai C. Electrocardiographic findings in experimental murine myocarditis--arrhythmias in the chronic stage. Jpn Circ J. 1983;47:1317-21. Koplan BA, Soejima K, Baughman K, et al. Refractory ventricular tachycardia secondary to

Kuhl U, Pauschinger M, Schwimmbeck PL, et al. Interferon-beta treatment eliminates

Kuhl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation 2005; 112: 1965-1970. Leone O, Rapezzi C, Sinagra G, Angelini A, Arbustini E, Bartoloni G, Basso C, Caforio AL,

Liu, P, Aitken, K, Kong, YY*, et al.* The tyrosine kinase p56lck is essential in coxsackievirus

Magnani JW, Danik HJ, Dec GW, Jr., DiSalvo TG. Survival in biopsy-proven myocarditis: a

Mahrholdt H, Goedecke H, Wagner A et al. Cardiovascular magnetic resonance assessment

Matsumori A, Kishimoto C, Kawai C, Sawada S. Right ventricular aneurysms complicating encephalomyocarditis virus myocarditis in mice. Jpn Circ J. 1983;47:1322-4. Muratore CA, Baranchuk A. Current and emerging therapeutic options for the treatment of chronic chagasic cardiomyopathy. Vasc Health Risk Manag 2010;6:593-601. Neumann DA, Rose NR, Ansari AA,Herskowitz A. Induction of multiple heart

Ohkubo K, Watanabe I, Okumuru Y et al. Right ventricular histological substrate and conduction delay in patients with Brugada Syndrome. Int J Cardiol 2010;51:17-23). Ordovas KG, Reddy GP, Higgins CB. MRI in nonischemic acquired heart disease. J Magn

Ott P, Marcus FI, Sobonya RE, Morady F, Knight BP, Fuenzalida CE. Cardiac sarcoidosis

Pankuweit S, Portig I, Lottspeich F,Maisch B. Autoantibodies in sera of patients with

Pieroni M, Dello Russo A, Marzo F, et al. High prevalence of myocarditis mimicking

and N-terminal sequence analysis. J Mol Cell Cardiol 1997; 29: 77-84. Phillips MP, Robinowitz M, Higgins JR, et al. Sudden cardiac death in Air Force recruits.

Patologia Cardiovascolare Italiana. G Ital Cardiol. 2009;10:3S-50S

B3-mediated heart disease. Nat Med 2000; 6: 429-434.

autoimmune myocarditis. J Immunol 1994; 152: 343-350.

predictors. Am Heart J 2006;151:463-70.

Circulation 2004;109:1250-8.

Reson Imaging. 2008;27:1195–213.

2003;26:1498-503.

2009;53:681-9.

JAMA 1986;256:2696-2699.

cardiac sarcoid: electrophysiologic characteristics, mapping, and ablation. Heart

cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction.

Calabrese F, Coccolo F, d'Amati G, Mariesi E, Milanesi O, Nodari S, Oliva F, Perkan A, Prandstraller D, Pucci A, Ramondo A, Silvestri F, Valente M, Thiene G; Federazione Italiana di Cardiologia; Associazione per la Patologia Cardiovascolare Italiana. Consensus document on endomyocardial biopsy of the Associazione per la

long-term retrospective analysis of the histopathologic, clinical, and hemodynamic

of human myocarditis: comparison to histology and molecular pathology.

autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced

masquerading as right ventricular dysplasia. Pacing Clin Electrophysiol.

myocarditis: characterization of the corresponding proteins by isoelectric focusing

arrhythmogenic right ventricular cardiomyopathy differential diagnosis by electroanatomic mapping-guided endomyocardial biopsy. J Am Coll Cardiol


Fabre A, Sheppard MN. Sudden adult death syndrome and other non-ischaemic causes of

Fabre A, Sheppard MN. Sudden adult death syndrome and other non-ischaemic causes of

Friedman RA, Kearney DL, Moak JP, Fenrich AL, Perry JC. Persistence of ventricular

Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, White JA,

Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological substrate in patients with clinical

Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of

Frustaci A, Verardo R, Caldarulo M, Acconcia MC, Russo MA, Chimenti C. Myocarditis in

Granér M, Lommi J, Kupari M, Raisanen-Sokolowski A, Toivonen L. Multiple forms of

Hama Y, Funabashi N, Ueda M, et al. Right-sided heart wall thickening and delayed

Henz BD, do Nascimento TA, Dietrich Cde O, et al. Simultaneous epicardial and

Hofmann R, Trappe HJ, Klein H, Kemnitz J. Chronic (or healed) myocarditis mimicking arrhythmogenic right ventricular dysplasia. Eur Heart J 1993;14:717–20. Hoshino T, Matsumori A, Kawai C, Imai J. Electrocardiographic abnormalities in Syrian golden hamsters with coxsackievirus B1 myocarditis. Jpn Circ J 1982;46:1305-12. Hoshino T, Matsumori A, Kawai C, Imai J. Ventricular aneurysms and ventricular

Jefic D, Joel B, Good E, Morady F, Rosman H, Knight B, Bogun F. Role of radiofrequency

Kettering K, Kampmann C, Mollnau H, Kreitner KF, Munzel T, Weiss C. Catheter ablation

an adolescent with subacute myocarditis. Clin Res Cardiol 2009;98:66-70.

monomorphic ventricular tachycardia. Circulation 2009;119:e200-3.

cardiomyopathy. J Interv Card Electrophysiol 2009;26:195-205.

myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009;53:1475-87. Frustaci A, Bellocci F, Olsen EG. Results of biventricular endomyocardial biopsy in

phenotype of Brugada syndrome. Circulation 2005;112:3680 –7.

cardiomyopathy: the TIMIC study. Eur Heart J. 2009;30:1995-2002.

arrhythmia after resolution of occult myocarditis in children and young adults. J

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

survivors of cardiac arrest with apparently normal hearts. Am J Cardiol

immunosuppressive therapy in patients with virus-negative inflammatory

hypertrophic cardiomyopathy patients presenting acute clinical deterioration. Eur

sustained monomorphic ventricular tachycardia as common presentation in giant-

enhancement caused by chronic active myocarditis complicated by sustained

endocardial substrate mapping and radiofrequency catheter ablation as first-line treatment for ventricular tachycardia and frequent ICD shocks in chronic chagasic

arrhythmias complicating Coxsackie virus B1 myocarditis of Syrian golden

catheter ablation of ventricular tachycardia in cardiac sarcoidosis: report from a

of an incessant ventricular tachycardia originating from the left aortic sinus cusp in

sudden cardiac death. Heart. 2006 Mar;92(3):316-20.

Feldman AM, McNamara D. Myocarditis. N Engl J Med. 2000;343:1388–98.

sudden cardiac death. Heart. 2006;92:316-20.

Am Coll Cardiol 1994;24:780-3.

1994;74:890-5.

Heart J. 2007;28:733-40.

cell myocarditis. Heart 2007;93:119-21.

hamsters. Cardiovasc Res. 1984;18:24-9.

multicenter registry. Heart Rhythm. 2009;6:189-95.


**19** 

**Acute Myocarditis – A Trigger of** 

**Autoantibodies (ETiCS) Study** 

*Comprehensive Heart Failure Centre CHFC/IFB, Würzburg,* 

**Expected Insights from the Etiology, Titre-**

*University Hospital of Würzburg, Department of Internal Medicine I, Cardiology,* 

Progressive cardiac dilatation and pump failure of unknown aetiology - termed "idiopathic" dilated cardiomyopathy (DCM) (Richardson et al., 1996; Maron et al., 2006) - represents one of the main causes of severe heart failure in Western populations with an annual incidence of about 100 and a prevalence of 300-400 patients per year (American Heart Association, 2009). The large majority of cases are thought to arise from an initial (mostly viral) infection leading to acute myocardial inflammation. Acute myocarditis may either heal (about one third of the cases) or progress to a chronic inflammatory process with continued fibrotic repair, subsequent dilatation of the left and/or right ventricle and –finally– severe congestive heart failure (about another third of the patients). Progression to DCM appears to occur particularly, when associated (a) with chronic inflammation of the myocardium due to viral persistence (Kühl et al., 2005) and/or (b) with the development of autoantibodies directed against distinct sarcoplasmatic or myocyte membrane proteins that are essential for cardiac function (Freedman & Lefkowitz, 2004; Jahns et al., 2006). The latter findings are further strengthened by the fact that patients with DCM often have alterations in both, their innate and their adaptive immune system (Limas, 1997; Luppi et al., 1998; Jahns et al., 2006; Mahrholdt et al., 2006). Thus, under certain conditions an initial acute inflammatory reaction may proceed into a kind of low-grade inflammation (MacLellan & Lusis, 2003) facilitating the development of abnormal or misled immune responses to the primary (infectious)

Nikolas Deubner1, Valérie Biovin2, Alida L.P. Caforio3, Stephan B. Felix4, Michael Fu5, Martin J. Lohse2,

*1 University Hospital of Würzburg, Department of Internal Medicine I,Cardiology, Comprehensive Heart Failure* 

*3 University of Padua, Division of Cardiology, Dpt. of Cardiologic, Thoracic and Vascular Sciences, Padua, Italy;* 

*2 University of Würzburg, Institute for Pharmacology and Toxicology, Würzburg, Germany;* 

*4 University of Greifswald, Department of Internal Medicine B – Cardiology, Greifswald,Germany; 5 University of Gothenburg, Department of Molecular and Clinical Medicine, Gothenburg, Sweden.* 

**1. Introduction** 

 \*

and Georg Ertl1

*Centre CHFC/IFB, Würzburg, Germany;* 

**Course, and Effect on Survival of Cardiac** 

**Cardiac Autoimmunity?** 

Roland Jahns et al.\*

*Germany* 

