William C. Roberts

Prevention Conference V Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Noninvasive Tests of Atherosclerotic Burden : Writing Group III

Writing Group I of Prevention Conference V considered the role of routine office-based measures for assessing global risk in asymptomatic persons. With the physician-directed office risk assessment as a foundation, further risk stratification may be valuable, especially when the risk estimate is neither clearly low risk nor high risk (intermediate risk). For the intermediate-risk patient, further testing might include ≥1 noninvasive measure of atherosclerotic burden. Pathology studies have documented that levels of traditional risk factors are associated with the extent and severity of atherosclerosis. However, at every level of risk factor exposure, there is substantial variation in the amount of atherosclerosis. This variation in disease is probably due to genetic susceptibility; combinations and interactions with other risk factors, including life habits; duration of exposure to the specific level of the risk factors; and such factors as biological and laboratory variability. Thus, subclinical disease measurements, representing the end result of risk exposures, may be useful for improving coronary heart disease (CHD) risk prediction. Noninvasive tests such as carotid artery duplex scanning, electron beam–computed tomography (EBCT), ultrasound-based endothelial function studies, ankle/brachial blood pressure ratios, and magnetic resonance imaging (MRI) techniques offer the potential for directly or indirectly measuring and monitoring atherosclerosis in asymptomatic persons. High-sensitivity testing for C-reactive protein (hs-CRP) may also represent a measure of atherosclerosis “burden” and may therefore be considered another potential marker of atherosclerosis disease risk. The Prevention Conference V participants considered the status of several measures of subclinical disease in CHD risk assessment. The discussion that follows is a summary of the data reviewed and discussed at Prevention Conference V. During the discussion groups at Prevention Conference V, the ankle-brachial blood pressure index (ABI) was considered as a means of predicting CHD events. The ABI is a simple, inexpensive diagnostic test for lower-extremity peripheral arterial disease (PAD). …

NIH CONFERENCE. THE IDIOPATHIC HYPEREOSINOPHILIC SYNDROME. CLINICAL, PATHOPHYSIOLOGIC, AND THERAPEUTIC CONSIDERATIONS

Abstract The idiopathic hypereosinophilic syndrome (HES) represents a heterogeneous group of disorders with the common features of prolonged eosinophilia of an undetectable cause and organ system d...The idiopathic hypereosinophilic syndrome (HES) represents a heterogeneous group of disorders with the common features of prolonged eosinophilia of an undetectable cause and organ system dysfunction. Fifty patients with the idiopathic HES were studied over 11 years of the National Institutes of Health. Multiple organ systems were involved; bone marrow hypereosinophilia was common to all patients, but the most severe clinicopathologic involvement was of the heart and nervous system. Postmortem gross pathologic examination of the hearts of patients with idiopathic and nonidiopathic HES suggested that the common mechanism of cardiac disease is the eosinophilia. Endomyocardial biopsy findings showed that the endothelial cells in the endocardium and of the microvasculature were the primary targets of the tissue damage. This damage initiates thrombosis; endocardial fibrosis and restrictive endomyocardopathy may follow. In-vitro culture of circulating eosinophil colony-forming units showed some normal studies, some studies showing increased progenitor cells committed to eosinophil development, and others showing an excess production of eosinophil colony-stimulating factor. Chemotherapy to lower the eosinophil counts has resulted in marked improvement of HES prognosis, as have agressive medical and surgical approaches to cardiovascular complications.

Sudden death in young athletes.

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...

Coronary Artery Narrowing in Coronary Heart Disease: Comparison of Cineangiographic and Necropsy Findings

Of 10 patients with fatal coronary heart disease undergoing coronary angiography 0 to 69 d (average, 21) before necropsy, the amount of narrowing in 61 coronary arteries observed angiographically (diameter reduction) during life by three angiographers was compared with that observed histologically (cross-sectional area) at necropsy. No overestimations of the degree of narrowing were made angiographically. Of 11 coronary arteries or their subdivisions narrowed 0 to 50% in cross-sectional area histologically, none were underestimated angiographically; of eight narrowed 51% to 75% histologically, seven had been underestimated, and of 42 narrowed 76% to 100% histologically, 17 were underestimated angiographically. The coronary atherosclerotic plaquing was diffuse (greater than 25% cross-sectional area narrowing) in 90% of 467 five-millimetre segments of coronary artery examined (24 cm per patient), and this diffuseness of the atherosclerotic process seems to be the major reason for angiographic underestimation of coronary narrowings.

The heart in systemic lupus erythematosus and the changes induced in it by corticosteroid therapy: A study of 36 necropsy patients

The natural history of the cardiovascular manifestations of systemic lupus erythematosus (SLE) have been altered by corticosteroids which exert their own cardiovascular effects. This study describes clinical and necropsy observations in 36 corticosteroid-treated patients with SLE and compares them to necropsy observations in patients with SLE reported before the use of corticosteroid therapy. The 36 patients averaged 32 years of age, and 33 were women. Systemic hypertension was present in 25 (69 per cent) and left ventricular hypertrophy in 23 (64 per cent) patients. Hypertension was twice as common in the 19 patients who received this drug for more than 12 months (average 38 months) than in the 17 patients who received this drug for less than 12 months (average 6 months), and was almost five times more common among our patients than in patients with SLE in the presteroid era. Congestive cardiac failure occurred in 15 patients (43 per cent), eight times more frequent than that reported in noncorticosteroid-treated patients with SLE. Subepicardial and myocardial fat was increased in all 36 patients. Lupus carditis was similar in frequency but differed morphologically in our patients compared to those not treated with corticosteroids. Libman-Sacks-type endocardial lesions, present in 18 (50 per cent) of our patients, were smaller, fewer in number, univalvular rather than multivalvular, and mainly left-sided. Most verrucae were either partly or completely healed, and some were calcified. Pericarditis, present in 19 (53 per cent) patients, was predominantly of the fibrous type. Myocarditis was present in three patients, each of whom also had endocarditis and pericarditis. The lumen of at least one of the three major coronary arteries was narrowed more than 50 per cent by atherosclerotic plaques in 42 per cent of the 18 patients who received corticosteroids for more than 1 year, but in none of the 17 patients who received corticosteroids for less than 1 year. Four of the eight patients with narrowed coronary arteries had myocardial infarcts. Although vital to the management of SLE, corticosteroids have an over-all deleterious effect on the heart. Systemic hypertension and left ventricular hypertrophy appear or, when present, worsen; congestive cardiac failure increases; epicardial apartment of Me

Intramural (“small vessel”) coronary artery disease in hypertrophic cardiomyopathy

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)

Frequency by Decades of Unicuspid, Bicuspid, and Tricuspid Aortic Valves in Adults Having Isolated Aortic Valve Replacement for Aortic Stenosis, With or Without Associated Aortic Regurgitation

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 (mean±SD, 70±12), 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.

Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

To evaluate cellular and protein components in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP), limited broncho-alveolar lavage was done in 58 patients (19 IPF, 7 CHP, and 32 controls). Analysis of the cells and protein in the lavage fluids from patients with IPF revealed an inflammatory and eosinophilic response and a significant elevation of IgG in the lungs. With corticosteroid therapy, inflammation diminished but eosinophils remained. Lavage fluid from patients with CHP also had eosinophils and elevated levels of IgG. However, in contrast to IPF, lavage fluid from CHP patients contained IgM, fewer inflammatory cells, and a strikingly increased number (38-74%) of lymphocytes. Identification of lavage lymphocytes in CHP showed that T lymphocytes were significantly elevated and B lymphocytes were decreased compared to peripheral blood. These studies suggest nthat the lung in IPF and CHP may function as a relatively independent immune organ, and that analysis of cells and proteins in broncho-alveolar lavage fluid may be of diagnostic, therapeutic, and investigative value in evaluating patients with fibrotic lung disease.

Sudden death in hypertrophic cardiomyopathy: a profile of 78 patients.

The clinical profile of 78 patients with hypertrophic cardiomyopathy who died suddenly (or experienced cardiac arrest and survived) was analyzed. At the time of cardiac catastrophe, 71% of the patients were younger than 30 years of age, 54% were without functional limitation and 61% were performing sedentary or minimal physical activity. Nineteen of the 78 patients (24%) were taking propranolol in apparently adequate dosages, indicating that this drug does not provide absolute protection against sudden death. No clinical or morphologic variable was particularly reliable in identifying patients at risk for sudden death. Forty-eight of 62 patients (77%) who died suddenly had a markedly increased ventricular septal thickness of 20 mm or more; however, mean septal thickness was similar in patients who died suddenly (25.2 +/- 0.9 mm) and in age- and sex-matched control patients with hypertrophic cardiomyopathy who have survived (23.6 +/- 0.8 mm). An abnormal ECG was present as often in patients who died suddenly as in control patients who have survived, (51 or 53, 96%). In addition, no particular cardiac symptom or hemodynamic variable (such as the magnitude of left ventricular outflow tract obstruction under basal conditions or left ventricular end-diastolic pressure) was characteristic of the patients with hypertrophic cardiomyopathy who died suddenly.

Idiopathic dilated Cardiomyopathy: Analysis of 152 necropsy patients

Certain clinical and cardiac necropsy findings are described in 152 patients aged 16 to 78 years (mean 45) with idiopathic dilated cardiomyopathy: 109 (72%) were men and 43 (28%) were women. Compared with the women, the men had a significantly (p less than 0.05) shorter mean duration of chronic congestive heart failure (CHF) (43 vs 69 months), a higher percentage of habitual alcoholism (40 vs 24%) and a higher mean heart weight (632 vs 551 g). The male to female ratio among the 58 known alcoholics was 7.3:1 and among the 70 known nonalcoholics, 1.5:1 (p less than 0.05). The mean duration of clinical evidence of CHF was similar among the known alcoholics and the known non-alcoholics (each 50 months). Of the 152 patients, 148 (97%) had clinical evidence of chronic CHF; in 114 patients it was the initial manifestation of idiopathic dilated cardiomyopathy, and in most it became intractable and caused death. The interval from onset of chronic CHF to death (known in 120 patients) ranged from 1 to 264 months (mean 54). Comparison of the 27 patients surviving greater than 72 months after onset of chronic CHF to the 64 patients surviving less than or equal to 36 months disclosed a significantly higher frequency in the longer survival group of older patients, of women, of habitual alcoholics, of patients with chest pain syndromes, diabetes mellitus, pulmonary emboli, of patients treated with warfarin and of patients with larger hearts at necropsy. Each of the 4 patients without chronic CHF died suddenly and sudden death was the initial manifestation of idiopathic dilated cardiomyopathy in them. An additional 33 patients also died suddenly, but each of them previously had had chronic CHF. Of the 79 patients (of the 131 for whom information was available) with either pulmonary or systemic emboli or both, 67 (85%) had either right- or left-sided thrombi or mural endocardial plaques or both, whereas of the 52 patients without emboli, 36 (69%) had intracardiac thrombi or plaques (p less than (0.05). Electrocardiograms in the last 6 months of life in 101 patients disclosed atrial fibrillation in 25; complete left (41 patients) or right (6 patients) bundle branch block or indeterminate intraventricular conduction delay (4 patients) in 51 patients; QRS voltage indicative of ventricular hypertrophy in 44 patients (left ventricular in 39 patients.(ABSTRACT TRUNCATED AT 400 WORDS)