Background-Aortic valve stenosis (with or without aortic regurgitation and without associated mitral stenosis) in adults in the Western world has been considered in recent years to most commonly be the result of degenerative or atherosclerotic disease. Methods and Results-We examined operatively excised, stenotic aortic valves from 932 patients aged 26 to 91 years (meanϮSD, 70Ϯ12), and none had associated mitral valve replacement or evidence of mitral stenosis: A total of 504 (54%) had congenitally malformed valves (unicuspid in 46 [unicommissural in 42; acommissural in 4] and bicuspid in 458); 417 (45%) had tricuspid valves (either absent or minimal commissural fusion); and 11 (1%) had valves of undetermined type. It is likely that the latter 11 valves also had been congenitally malformed. Of the 584 men, 343 (59%) had either a unicuspid or a bicuspid valve; of the 348 women, 161 (46%) had either a unicuspid or a bicuspid aortic valve. Conclusions-The data from this large study of adults having isolated aortic valve replacement for aortic stenosis (with or without associated aortic regurgitation) and without associated mitral stenosis or mitral valve replacement strongly suggest that an underlying congenitally malformed valve, at least in men, is more common than a tricuspid aortic valve.

The causes of sudden and unexpected death in 29 highly conditioned, competitive athletes, ages 13-30 years, are summarized. Sudden death occurred during or just after severe exertion on the athletic field in 22 of the 29 athletes. Structural cardiovascular abnormalities were identified at necropsy in 28 of the 29 athletes (97%), and in 22 (76%) were almost certainly the cause of death. The most common cause of death in this series was hypertrophic cardiomyopathy, which was present in 14 athletes. Other cardiovascular abnormalities that occurred in more than one athlete were anomalous origin of the left coronary artery from the right (anterior) sinus of Valsalva, idiopathic concentric left ventricular hypertrophy, coronary heart disease and ruptured aorta. Cardiac disease was suspected during life in only seven of the 29 patients, and in only two of the seven was the correct diagnosis made clinically. Hence, in this series of young athletes, sudden death was usually due to structural cardiovascular disease, and hypertrophic cardiomyopathy was a frequent cause of sudden death; atherosclerotic coronary heart disease was relatively uncommon.

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality.The clinical examination of individuals with MPS is often difficult due to physical and, sometimes, intellectual patient limitations. The absence of precordial murmurs does not exclude the presence of cardiac disease. Echocardiography and electrocardiography are key diagnostic techniques for evaluation of valves, ventricular dimensions and function, which are recommended on a regular basis. The optimal technique for evaluation of coronary artery involvement remains unsettled.Standard medical and surgical techniques can be modified for MPS patients, and systemic therapies such as hematopoietic stem cell transplantation and enzyme replacement therapy (ERT) may alter overall disease progression with regression of ventricular hypertrophy and maintenance of ventricular function. Cardiac valve disease is usually unresponsive or, at best, stabilized, although ERT within the first few months of life may prevent valve involvement, a fact that emphasizes the importance of early diagnosis and treatment in MPS.

Many patients with hypertrophic cardiomyopathy have signs and symptoms of myocardial ischemia and dysfunction. Although hypertrophy and increased left ventricular pressure can account for such abnormalities, altered small intramural coronary arteries have also been described in such patients. To determine the prevalence and extent as well as the clinical relevance of abnormal intramural coronary arteries, a histologic analysis of left ventricular myocardium obtained at necropsy was performed in 48 patients with hypertrophic cardiomyopathy (but without atherosclerosis of the extramural coronary arteries) and in 68 control patients with either a normal heart or acquired heart disease. In hypertrophic cardiomyopathy, abnormal intramural coronary arteries were characterized by thickening of the vessel wall and a decrease in luminal size. The wall thickening was due to proliferation of medial or intimal components, or both, particularly smooth muscle cells and collagen. Of the 48 patients with hypertrophic cardiomyopathy, 40 (83%) had abnormalities of intramural coronary arteries located in the ventricular septum (33 patients), anterior left ventricular free wall (20 patients) or posterior free wall (9 patients); an average of 3.0 +/- 0.7 abnormal arteries were identified per tissue section. Altered intramural coronary arteries were also significantly more common in tissue sections having considerable myocardial fibrosis (31 [74%] of 42) than in those with no or mild fibrosis (31 [30%] of 102; p less than 0.001). Abnormal intramural coronary arteries were also identified in three of eight infants who died of hypertrophic cardiomyopathy before 1 year of age. In contrast, only rare altered intramural coronary arteries were identified in 6 (9%) of the 68 control patients (0.1 +/- 0.05 abnormal arteries per section; p less than 0.001) and those arteries showed only mild thickening of the wall and minimal luminal narrowing. Moreover, of those patients with abnormal intramural coronary arteries, such vessels were about 20 times more frequent in patients with hypertrophic cardiomyopathy (0.9 +/- 0.2/cm2 myocardium) than in control patients (0.04 +/- 0.02/cm2 myocardium). Hence, abnormal intramural coronary arteries with markedly thickened walls and narrowed lumens are present in increased numbers in most patients with hypertrophic cardiomyopathy studied at necropsy and may represent a congenital component of the underlying cardiomyopathic process.(ABSTRACT TRUNCATED AT 400 WORDS)

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