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European Heart Journal Advance Access originally published online on May 9, 2007
European Heart Journal 2007 28(11):1326-1333; doi:10.1093/eurheartj/ehm076
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis

Alida L.P. Caforio1,*, Fiorella Calabrese2, Annalisa Angelini2, Francesco Tona1, Annalisa Vinci1, Stefania Bottaro1, Angelo Ramondo1, Elisa Carturan2, Sabino Iliceto1, Gaetano Thiene2 and Luciano Daliento1

1 Division of Cardiology, Department of Cardiological, Thoracic, and Vascular Sciences, University of Padova-Policlinico, Centro ‘V. Gallucci’, Via Giustiniani 2, 35128 Padova, Italy
2 Institute of Pathological Anatomy, University of Padua, Padua, Italy

Received 6 October 2006; revised 23 February 2007; accepted 8 March 2007; online publish-ahead-of-print 9 May 2007.

* Corresponding author. Tel: +3949 821 2348; fax: +3949 876 1764. E-mail address: alida.caforio{at}unipd.it

See page 1279 for the editorial comment on this article (doi:10.1093/eurheartj/ehm111)

Aims: Myocarditis may be idiopathic, viral, and/or immune; frequency of these forms and prognosis are ill-defined. We aimed at identifying aetiopathogenetic and prognostic markers in myocarditis, including viral genome on endomyocardial biopsy (EMB) by polymerase chain reaction (PCR) and serum anti-heart autoantibodies (AHA).

Methods and results: We studied 174 patients, 110 males, aged 36 ± 18 years, median follow-up 23.5 months, range 10–54; 85 patients had active myocarditis and 89 borderline myocarditis (no diffuse or severe inflammation) (Dallas criteria). Serum AHA were detected by indirect immunofluorescence. PCR was used to detect virus. Six-year actuarial survival was 73%. AHA were found in 56% of patients and positive PCR in 26%. Univariate predictors of death/transplantation were young age, longer symptom duration, giant cell myocarditis, NYHA II–IV, positive PCR, presentation with LV dysfunction, clinical signs/symptoms of heart failure, and echocardiographic and haemodynamic indexes of cardiac dysfunction. By Cox univariate analysis, highest risk was conferred by clinical signs/symptoms of left (HR = 4.3, CI 1.7–10.8, P = 0.002) and right heart failure (HR 3.4, CI 1.5–7.3, P = 0.002).

Conclusion: In myocarditis, biventricular dysfunction at diagnosis was the main predictor of death/transplantation. AHA identified immune-mediated myocarditis in the majority of cases. Viral genome was a univariate predictor of adverse prognosis. Our approach of using AHA and positive PCR as aetiopathogenetic markers should help patient selection and recruitment in future studies on aetiological therapy.

Key Words: Cardiomyopathy • Myocarditis • Antibodies • Immunology


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