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.

[Myocardial infarction and oral contraceptives]. / Infarctus du myocarde et contraceptifs oraux.

Shortly after the introduction of oral contraceptives in 1960, myocardial infarction (MI) started to emerge as a major adverse effect. Its mechanism and pathophysiology have remained elusive. Many epidemiological studies identified smoking, hypertension, diabetes and hypercholesterolemia as risk factors for coronary thrombosis in young women using oral contraceptives. The pathogenesis of MI involves two phases: atherosclerotic plaque formation, and thrombotic arterial occlusion. The use of very low doses of estrogen (less than 50 microg of ethinyl estradiol) and new progestagens have minimized the vascular risks. However, the risk remains in women who smoke or have other atherosclerotic risks factors. We report 12 cases of MI in women aged 35 +/- 5 years who were using different types of oral contraceptive. All the women had several risks factors, such as smoking, hypertension, hypercholesterolemia, obesity, and type II diabetes. Coronarography during the acute phase showed either occlusions on severe atherosclerotic stenoses or thrombosis of arteries with non significant atherosclerotic plaque. In two cases coronarography was normal after thrombolysis. Ten women recovered without sequelae, but reversible left ventricular dysfunction occurred in the other two women, who did not have acute-phase revascularization. Recent case-control studies show that the cardiovascular risk is very low with new, third-generation combined contraceptives. But the risk of MI increases with age, smoking, hypertension, dyslipidemia and diabetes. The absolute risks associated with oral contraceptives and smoking are higher in women over 35, because of the steeply rising incidence of atherosclerosis. It is mandatory to respect the classical contraindications of oral contraception.