Author + information
- Ulrich W. Kolck, MD,
- Kirsten Alfter, MD,
- Jürgen Homann, MD,
- Ivar von Kügelgen, MD and
- Gerhard J. Molderings, MD⁎ ()
- ↵⁎Institute of Pharmacology and Toxicology, University of Bonn, Reuterstrasse 2b, D-53113 Bonn, Germany
Kim et al. (1) reported that in patients with chronic heart failure (CHF), the H2-histamine receptor antagonist famotidine improved both cardiac symptoms and ventricular remodeling, which was suggested to be an indirect hint for a role of histamine and its receptors in the failing heart. More direct conclusions might be deduced from investigations of patients with systemic mastocytosis who have an increased myocardial histamine concentration due to an increased mast cell density in the heart. Here we report findings observed in 17 patients with systemic mast cell activation disorder (2) who, among other symptoms, had a mast cell mediator-induced tachycardia indicating a significant infiltration in the heart by pathologically activated mast cells. One should expect that, because of the long time course of the disease (median duration of illness: 14 years), a contribution of a continuously increased histamine concentration in the heart should have become observable in those patients. In echocardiography, left ventricular diastolic and systolic diameter, fractional shortening, and ejection fraction were not pathologically altered in our patients. However, a diastolic left ventricular dysfunction occurred in 12 of 17 patients as determined by pulse wave- and/or tissue-Doppler imaging, which represents a sensitive first sign of a myocardial textural alteration. In 5 of those 12 patients a left ventricular hypertrophy was observed. Because of the absence of other precipitating factors, these alterations are probably due to the remodeling effect of prohypertrophic cytokines and proteases and profibrotic growth factors synthesized and secreted by mast cells (3).
In conclusion, our findings do not support the contention that an increased myocardial histamine concentration alone, even over a long period, leads to CHF because of a direct effect on the cardiac myocytes. The beneficial effect of the H2-histamine receptor antagonist famotidine on CHF described by Kim et al. (1) may rather indicate an indirect role of histamine in the evolution and progression of CHF. In this context, it is conceivable that H2-histamine receptor antagonists may reduce the activity of the mast cells in the heart by blocking H2-histamine receptors on them and, thereby, may reduce release of those mast cell mediators which, according to animal experiments and to our aforementioned findings, can induce a remodeling of the heart with an associated functional distortion.
- American College of Cardiology Foundation