Drug-induced aortic valve stenosis: An under recognized entity.

BACKGROUND: We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS. METHODS: Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient >15mmHg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria. RESULTS: Twenty-five (19 females, mean age 62years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13mmHg. Aortic regurgitation was ≥ mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD. CONCLUSION: The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS.

Valvular heart disease associated with long-term treatment by methysergide: a case report.

This case report concerns a woman treated continuously since at least 10 years by methysergide for cluster headache. The echocardiographic and histological features of the severe valve fibrosis presented by this patient are very similar to those described with 5 HT(2B) receptors agonistic drugs.

[Preventive medication in migraine headache : Individualized clinical pathways]. / Medikamentöse Prophylaxe der Migräne : Individuelle Behandlungspfade.

With the introduction of the highly effective triptans in the treatment of acute migraine attacks, the significance of migraine prevention temporarily lost ground in the awareness of doctors and, even more so, patients. This was unjustified, as the increasing numbers of patients with triptan-overuse headache clearly demonstrated. Recent years have seen this trend reversed with a resurgence of migraine prevention. In daily practice the first question is whether migraine prevention is indeed indicated for the patient. If answered affirmatively, the next step is the intricate selection of the most promising agent for the patient. Treatment guidelines regularly updated by the relevant medical societies provide a general overview of the agents principally available according to the principles of evidence-based medicine. Yet, low compliance rates suggest that in practice implementation of these guidelines may have to be tailored to the patient in question. The treatment algorithm presented here tries to bridge the gulf between general treatment guidelines and the actual needs of the patient. From this, feasible clinical pathways are derived for individualized treatment.

Drug-induced fibrotic valvular heart disease.

The initial association between the development of valvular heart disease and drugs stems from observations made during the use of methysergide and ergotamine for migraine prophylaxis in the 1960s. Since then, the appetite suppressants fenfluramine and dexfenfluramine, the dopamine agonists pergolide and cabergoline, and more recently, the recreational drug ecstasy (3,4 methylenedioxymethamphetamine; MDMA) have been implicated. Results from clinical trials show that drug dose and treatment duration affect both the risk of developing the disease and its severity. The natural history of the disease remains unclear, although regression of valvular lesions after the end of treatment has been reported. Interference with serotonin metabolism and its associated receptors and transporter gene seems a likely mechanism for development of the drug-induced valvular heart disease. Physicians need to balance the benefits of continued therapy with these drugs against possible risks. Further investigation is needed to assist with treatment decisions. Continued vigilance is necessary because several commonly prescribed treatments interact with serotonergic pathways.

Methysergide-induced valvular heart disease: a report of 2 cases.

Methysergide is a serotonin antagonist and is used as a long-term prophylactic treatment for migraine. Although many patients experience adequate control of migraine episodes, methysergide has been reported to cause retroperitoneal and pleuropulmonary fibrosis. Cardiovascular side effects mainly in the form of valvular fibrosis have been less recognized. We report 2 cases of methysergide-related mitral valve fibrosis.

Pharmacological prevention of migraine: to be considered case by case.

(1) Migraines are characterized by recurrent headaches generally lasting between 4 and 72 hours and disappearing without complication. They can be incapacitating, owing to their frequency and/or intensity. (2) Many drugs have been used to prevent migraines. One of the most common outcome measures used in clinical trials is the proportion of responder patients, defined as those in whom the monthly frequency of migraines is at least halved. On average, about one-third of patients respond to placebo in clinical trials. (3) Propranolol is the betablocker with the best-documented efficacy: in absolute terms the response rate is about 30% higher than with placebo. The adverse effects of betablockers are mainly cardiovascular and neuropsychological. (4) Valproic acid, an anticonvulsant, is about as effective as propranolol, and its adverse effects are generally acceptable. (5) Amitriptyline is the antidepressant with the best-documented preventive effects, with a response rate about 20% higher than placebo. Its principal adverse effects are due to its atropinic action. Amitriptyline can also have a sedative effect. (6) Flunarizine also has documented efficacy, but this "hidden neuroleptic" can cause extrapyramidal disorders and weight gain. (7) Among the serotonergic antagonists, methysergide has documented efficacy but long-term treatment can lead to serious retroperitoneal, pulmonary or cardiac fibrosis. Pizotifen causes drowsiness or weight gain in about 50% of patients. (8) The choice of preventive treatment for migraine must be based on the balance between efficacy (compared to placebo) and adverse effects. In practice, the first choice drug is propranolol. (9) Because the frequency of migraines fluctuates over time, withdrawal of prophylaxis should be attempted on a regular basis, with the patient's consent.

Mediastinal fibrosis causing myocardial ischemia.

This report describes an unusual etiology of coronary artery disease. A 60-year-old male presented with angina. He was treated with methysergide for migraine. It was determined that the patient possessed an extremely thick-walled ascending aorta that caused the coronary ostial narrowing. He underwent replacement of the ascending aorta and proximal aortic arch. Double vessel coronary artery bypass grafting was performed using saphenous vein. Microscopic examination indicated the pathology to be sclerosing mediastinis.

Psychiatric side effects during methysergide treatment.

A patient is reported with psychological change characterised by impaired concentration and thought projection, followed by both severe anxiety and depression, starting after three weeks on high dose methysergide. The acute problem settled slowly after methysergide withdrawal and is likely to represent an unusual and serious side effect of that drug.

Drug-induced pleural disease.

Drug-induced pleural disease is uncommon and less known to clinicians than drug-induced parenchymal lung disease. Pleural reactions from drugs manifest as pleural effusions, pleural thickening, or pleuritic chest pain, and may occur in the absence of parenchymal infiltrates. The clinician should be cognizant of the possibility of a drug-induced pleural reaction. A detailed drug history, temporal relationship between symptom onset and initiation of therapy, and pleural fluid eosinophilia should raise the suspicion of a drug-related process. We suspect that as new drugs are marketed in the United States, the number of drugs that result in pleuropulmonary toxicity will continue to increase. Moreover, if the cause of an exudative pleural effusion is not clinically obvious after pleural fluid analysis, drug therapy withdrawal should be a consideration if clinically appropriate before initiating an extensive diagnostic evaluation that may entail unnecessary economic burden and discomfort for the patient.

[Current views on migraine and anti-migraine preparations]. / Sovremennye predstavleniia o migreni i mekhanizmakh deistviia sredstv dlia ee lecheniia i profilaktiki.

On the basis of comprehensive experimental and clinical research the authors defined a variety of migraine-related mechanisms and schemes of migraine-correction by drugs, which should be both of the vascular- and general-actions to ensure an effective medication.

Successful repair of aortic and mitral incompetence induced by methylsergide maleate: confirmation by intraoperative transesophageal echocardiography.

Methylsergide maleate, an effective anti-migraine medication, has a well-documented association with left-sided cardiac valve dysfunction. Prior reports have described cardiac valve dysfunction in patients using methylsergide chronically for a minimum of 6 years, with surgical intervention consisting of valve replacement for patients with intractable congestive heart failure. We report a 51-year-old woman who developed severe mitral and aortic valvular dysfunction after taking methylsergide maleate for migraine headaches for a period of 19 months, and who subsequently underwent aortic and mitral valve repair with excellent short-term results.

Fibrosis due to ergot derivatives: exposure to risk should be weighed up.

(1) Ergot derivatives are used for a variety of indications, including migraine, Parkinson's disease, endocrine disorders, and cognitive and neurosensory deficits in elderly people. (2) Fibrosis is a common complication of treatment with ergot derivatives. (3) Retroperitoneal fibrosis is the commonest form. Pleuropulmonary and pericardial fibrosis also occur. (4) Cardiac valve damage has been linked to some ergot derivatives. (5) Fibrosis occurs during long-term treatment. (6) Renal, pulmonary and cardiac complications can be serious. The fibrosis is often reversible if the drug is stopped quickly. (7) In practice, this risk of serious adverse effects tips the scales against these drugs for poorly established indications such as cognitive and neurosensory deficits in elderly people. The possibility of drug induced fibrosis should be considered at the first sign of renal, cardiac or pulmonary fibrosis in a patient on ergot derivatives.