Ann Thorac Surg 2003;76:2102-2104
© 2003 The Society of Thoracic Surgeons
Case report
Resolved hypersensitivity myocarditis after ventricular circulatory assist
Florian Grabellus, MDa,b*,
Andreas Hoffmeier, MDc,
Klaus J. Schmitz, MDa,
Reinhard Kandolf, MDd,
Burkhard D. Bültmann, MDd,
Hans-H. Scheld, MDc,
Hideo A. Baba, MDa,b
a Institute of Pathology, University of Essen, Essen, Germany
b Gerhard-Domagk-Institute of Pathology, Münster, Germany
c Department of Thoracic and Cardiovascular Surgery, University of Münster, Münster, Germany
d Institute of Pathology, University of Tübingen, Tübingen, Germany
Accepted for publication April 23, 2003.
* Address reprint requests to Dr Grabellus, Institute of Pathology, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany
e-mail: florian.grabellus{at}medizin.uni-essen.de
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Abstract
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Hypersensitivity myocarditis is known to be a cardiac manifestation of a delayed-type hypersensitivity response caused by drug treatment. In heart transplantation candidates the incidence is elevated. We report the case of a patient with end-stage heart failure who underwent implantation of a left ventricular assist device as a bridge to transplantation. The histologic investigation of the left ventricular specimen obtained during device implantation revealed the diagnosis of a hypersensitivity myocarditis. Ten months later this lesion showed complete reversibility within specimens of the explanted heart, maybe as a result of the termination of inotropic therapy after implantation of the left ventricular assist device.
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Introduction
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Hypersensitivity myocarditis is known to be a cardiac manifestation of an allergic reaction mainly caused by drug treatment. A multitude of drugs have been accused of being possible etiologic agents. The main offenders seem to be sulfonamides and methyldopa, as well as penicillin and its derivatives. The hypersensitive drug reaction is mediated by chemically reactive drug metabolites that bind to endogenous protein carriers and function as haptens. As a result of a delayed-type hypersensitivity response, T lymphocytes are activated, from which eosinophil-stimulating cytokines (eg, interleukin 5) are liberated [1, 2].
In heart transplantation candidates the incidence of hypersensitivity myocarditis is elevated, and inotropic substances like dobutamine are known to be common causes [3, 4]. The clinical findings are often minor and nonspecific and include allergic drug reaction with rash, fever, bronchospasm, and eosinophilia [5]. Cardiac symptoms may be present but vary in severity from chest discomfort and palpitations to electrocardiographic changes and dilatation of the cardiac chambers. In some cases the clinical features include infarction-like findings, acute heart failure, or abnormalities of the bundle of His with block formation and intractable ventricular tachycardia, rarely leading to sudden cardiac death [2, 5, 6].
The histopathologic diagnosis is mainly based on the combination of an interstitial eosinophil-rich infiltrate with lymphocytes, plasma cells, and histiocytes involving all layers of the heart wall in the form of a pancarditis and an absent or minor myocyte damage (Fig 1).
A nonnecrotizing vascular involvement is frequently present in areas of extensive infiltration, and in some cases granuloma-like lesions or giant cells may be present within the interstitium. Further examination methods such as immunohistochemical or molecular biological techniques have not been established so far. After withdrawal of the causative agent the majority of patients recover in a few days [1, 2, 6].
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Fig 1. Algorithm for diagnosis of eosinophilic heart diseases. It is based on morphologic features and available clinical and laboratory data.
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A 52-year-old man with a diagnosis of dilated cardiomyopathy and a standard oral heart failure therapy for 5 years exhibited the clinical signs of end-stage heart failure (New York Heart Association class III–IV) within 6 months and was listed for heart transplantation.
While on the waiting list the hemodynamic situation of the patient worsened rapidly under advanced heart failure therapy, and he was taken to the intensive care unit where a systemic positive inotropic therapy was started. Because of increasing doses of catecholamines the decision of an early implantation of a left ventricular assist device (LVAD) as a bridge to transplantation was made 3 days later. After LVAD implantation his hemodynamics markedly improved, and the inotropic support could be terminated. Ten months later the patient underwent orthotopic heart transplantation.
Signs of drug reactions such as fever, rash, or eosinophilia were not observed at any time.
The histologic examination of the transmural specimen collected from the left ventricular apex during LVAD implantation revealed a conspicuous interstitial inflammatory infiltrate in all layers of the heart wall (Fig 2A, 2B). This infiltrate consisted of lymphocytes, plasma cells, histiocytes, some mast cells, and a moderate percentage of eosinophils (20%). Single granuloma-like lesions with a central fibrinoid degeneration were present (Fig 2C). Myocyte damage was minor and a slight interstitial edema was observed.
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Fig 2. Histopathology of left ventricular specimen collected during implantation of the left ventricular assist device. (A) Eosinophil-rich inflammatory infiltrate within the interstitial spaces of the myocardium (Giemsa, x400). (B) Epicardial manifestation of the hypersensitivity myocarditis (hematoxylin & eosin, x200). (C) Two granuloma-like lesions (*) (hematoxylin & eosin, x400). (D, E) Histopathology of the heart at the time of implantation of the left ventricular assist device (D: hematoxylin & eosin, x400) and explantation of the left ventricular assist device plus heart transplantation (E: hematoxylin & eosin, x200). The eosinophilic infiltrates are completely resolved after left ventricular assist device support. (i= interstitium; m = myocardium; v = small vessels.)
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To make sure that an eosinophil-rich type of a viral myocarditis could be excluded we performed a polymerase chain reaction screening for viral genome on a paraffin-embedded myocardial specimen collected during LVAD implantation. This screening was negative for all relevant viruses.
After long-term circulatory support the initially observed eosinophilic inflammatory infiltrate was not present anymore, which was proved by histologic investigation of the explanted organ (Fig 2D, 2E). For this reason specimens of all four heart chambers, including transmural specimens of the left ventricular apex from close to the LVAD implantation area (Fig 2E), were investigated.
The
routine endomyocardial biopsies which were carried out for rejection diagnosis showed no recurrent myocardial tissue eosinophilia.
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Comment
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A variety of pharmacologic agents are known to be causes of hypersensitivity myocarditis in healthy persons. Sulfonamides, methyldopa, and penicillin and its derivatives seem to be the main offenders and account for up to 75% of cases [2, 6]. Hypersensitivity myocarditis in explanted hearts occurs in up to 22% of cases [3, 4]. In patients with end-stage heart failure, intravenous application of dobutamine has been accused of being a possible trigger for these findings [4].
Inasmuch as the clinical features of the hypersensitivity myocarditis are often minor and nonspecific and most of what is known about hypersensitivity myocarditis is from autopsy studies, the diagnosis of hypersensitivity myocarditis in this case was made accidentally within the transmural left ventricular specimen collected during LVAD implantation of a living patient. Surprisingly, the inflammatory infiltrates were completely resolved in the histopathologic investigation of the explanted heart after 10 months of mechanical circulatory support. Residues of myocardial damage such as an increase in interstitial fibrosis were not seen.
Examination of the patient's medications (Table 1)
revealed a prolonged intravenous dobutamine administration before LVAD implantation, which was, together with epinephrine, terminated after this operation and may be a plausible, well-known explanation for the course of the interesting histologic findings.
This report describes a reversible hypersensitivity myocarditis under left ventricular circulatory support, which was verified by histologic examination.
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Acknowledgments
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The authors thank Dorothe Moellmann, Maria Wolters, and Birgit Schulte for excellent technical assistance.
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References
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- Lewis L., Silver M.D. Adverse effects of drugs on the cardiovascular system. In: Silver M.D., Gotlieb A.I., Schoen F.J., eds. Cardiovascular pathology, 3rd ed New York: Churchill Livingstone, 2001:542-544.
- Fenoglio J.J., Jr, McAllister H.A., Jr, Mullick F.G. Drug related myocarditis. I. Hypersensitivity myocarditis. Hum Pathol 1981;12:900-907.[Medline]
- Gravanis M.B., Hertzler G.L., Franch R.H., et al. Hypersensitivity myocarditis in heart transplant candidates. J Heart Lung Transplant 1991;10:688-697.[Medline]
- Spear G.S. Eosinophilic explant carditis with eosinophilia:? hypersensitivity to dobutamine infusion. J Heart Lung Transplant 1995;14:755-760.[Medline]
- Hawkins E.T., Levine T.B., Goss S.J., Moosvi A., Levine A.B. Hypersensitivity myocarditis in the explanted hearts of transplant recipients. Reappraisal of pathologic criteria and their clinical implications. Pathol Annu 1995;30:287-304.
- Kounis N.G., Zavras G.M., Soufras G.D., Kitrou M.P. Hypersensitivity myocarditis. Ann Allergy 1989;62:71-74.[Medline]
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Abstract
Introduction
