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(Circulation. 2006;113:2-4.)
© 2006 American Heart Association, Inc.

Editorial

Serotonin Transporter Mechanisms and Cardiac Disease

Robert J. Levy, MD

From the Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, Pa.

Correspondence to Robert J. Levy, MD, Children’s Hospital of Philadelphia, Abramson Research Center, Suite 702, 3615 Civic Center Blvd, Philadelphia, PA 19104–4318. E-mail levyr@email.chop.edu

Key Words: Editorials • fibrosis • pathology • serotonin • valves

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Serotonin (5-HT)–related mechanisms have been explored extensively for pharmaceutical development, especially with regard to antidepressants and appetite suppressants. However, pharmacological agents acting through 5-HT-related pathways have been associated with a number of significant cardiovascular adverse effects, including pulmonary hypertension,^1,2 cardiac arrhythmias,² and cardiac valve abnormalities.^1–4 Evidence for a 5-HT valvulopathy has arisen from a variety of observations, including clinical,^3,4 animal model,⁵ and cell culture investigations.^6,7 Patients with carcinoid syndrome tumors,⁴ others treated with the diet drug combination fenfluramine-phentermine (Fen/Phen),³ and individuals treated with ergot derivatives⁸ have been observed to develop what is most likely a 5-HT valvulopathy with comparable heart valve pathology between these different clinical groupings. In patients with carcinoid syndrome tumors, high 5-HT levels were observed to be associated with fibrodysplasia affecting predominantly the right-side cardiac valves³; a comparable pattern of valve disease was observed in a number of reported patients treated with ergot derivatives.⁸ The reason for this right-side valvulopathy distribution (tricuspid and pulmonary valves) has been hypothetically attributed to pulmonary monoamine oxidase clearance of 5-HT, thereby resulting in left-side cardiac valves being exposed to relatively lower 5-HT levels^1,4 despite elevated systemic 5-HT. However, a recent animal study involving daily injection of 5-HT in rats demonstrated both elevated 5-HT levels and right- and left-side valve abnormalities.⁵

Article p 81

The Fen/Phen valvulopathy has been reported to affect both right- and left-side cardiac valves,³ and this was hypothesized to be due in part to pulmonary monoamine oxidase inhibition by Phen, resulting in increased 5-HT exposure for left-side . . . [Full Text of this Article]

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