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Biomedical subjects

E L Alderman

Publications and source records attributed to E L Alderman.

At least 73 records · Page 4Linked to original sources

Age variation in the association between angiographic coronary disease and angina from the Coronary Artery Surgery Study (CASS)

Between July 1974 and May 1979, 19,153 non-randomized patients without prior cardiac surgery and with chest pain were studied angiographically and enrolled in the Coronary Artery Surgery Study (CASS). The primary question addressed by this paper is: for fixed levels of coronary artery disease, are the presence and severity of angina pectoris greater for older than for younger patients? For those with the same extent of disease, older patients were more likely to have angina and to exhibit more severe symptoms. After adjustment for covariates using logistic regression analysis, age was found to be an important, independent predictor of the presence and severity of angina. There are many possible explanations for these findings, although physiologic factors related to aging, the disease process, and deconditioning associated with an increased sedentary life style seem most reasonable. Another possibility has to do with referral patterns for study and the prevalence of angina in the different age groups.

Adult↗

Morphology of left anterior descending coronary territory lesions as a predictor of anterior myocardial infarction: a CASS Registry Study.

Despite a growing awareness of the correlation of coronary artery stenoses morphology with clinical syndromes, no comprehensive, prospective analysis of the implications of stenosis morphology on risk of myocardial infarction has been reported. Angiograms from 118 patients, representative of the 4.9% of medically treated Coronary Artery Surgery Study (CASS) patients who during subsequent 3 year follow-up study had an anterior myocardial infarction, were matched on the basis of arteriographic anatomy and disease with 141 patients who did not have an anterior infarction. Angiograms from these 259 patients with 557 left anterior descending artery stenoses were reviewed without knowledge of clinical outcome. Conditional regression analyses were performed to determine the importance of stenosis morphology, relative to computer-determined stenosis severity and other clinical variables, in the prediction of risk of infarction. Univariate analysis revealed luminal roughness (odds ratio 4.5; p = 0.001) and lesion length (odds ratio 1.7 per unit length; p = 0.007) to be highly correlated with future risk of infarction. Multivariate analysis revealed left anterior descending artery percent stenosis greater than or equal to 50%, lesion roughness, left circumflex artery stenosis and smoking, in that order, to be predictive of anterior myocardial infarction, whereas 22 other morphologic variables were not independently predictive of outcome. The importance of stenosis roughness may relate to its propensity for thrombogenesis and should be considered in clinical decision making.

Angiography↗

Relation between longitudinal, circumferential, and oblique shortening and torsional deformation in the left ventricle of the transplanted human heart.

The present study was designed to investigate the anisotropy of systolic chord shortening in the lateral, inferior, septal, and anterior regions of the human left ventricle. At the time of surgery, 12 miniature radiopaque markers were implanted into the left ventricular midwall of the donor heart in 15 cardiac transplant recipients. Postoperative biplane cineradiograms were computer-analyzed to yield the three-dimensional coordinates of these markers at 16.7-msec intervals. In each of the four left ventricular regions, chords were constructed from a central marker to outlying markers, and the percent systolic shortening of each chord was calculated. In each region, chord angles were measured with respect to the circumferential direction (positive angles counterclockwise) and each chord was assigned to one of four angular groups: I. oblique, -45 +/- 22.5 degrees or 135 +/- 22.5 degrees; II. circumferential, 0 +/- 22.5 degrees or 180 +/- 22.5 degrees; III. oblique, 45 +/- 22.5 degrees or -135 +/- 22.5 degrees; or IV. longitudinal, 90 +/- 22.5 degrees. In the lateral, inferior, and septal regions, respectively, systolic shortening (mean +/- SD%) was significantly greater in Group I chords (19 +/- 5%, 17 +/- 5%, and 15 +/- 4%) than those in Group II (15 +/- 5%, 12 +/- 4%, and 11 +/- 4%), Group III (12 +/- 4%, 12 +/- 5%, and 11 +/- 4%), or Group IV (13 +/- 5%, 13 +/- 6%, and 12 +/- 5%). The anterior region was unique in exhibiting equal shortening in both Group I and Group II chords (16 +/- 5%), although the shortening of these chords was significantly greater than that of Group III and Group IV (12 +/- 5%) in this region. A cylindrical mathematical model was developed to relate longitudinal, circumferential, and oblique systolic shortening to torsional deformation about the long axis of the left ventricle. Torsional deformations measured in these 15 hearts were of sufficient magnitude and correct sense to agree with model predictions. These data suggest that torsional deformations of the left ventricle are of fundamental importance in linking the one-dimensional contraction of the helically wound myocytes to the three-dimensional anisotropic systolic shortening encountered in the transplanted human heart.

Biomechanical Phenomena↗

Prevalence of accelerated coronary artery disease in heart transplant survivors. Comparison of cyclosporine and azathioprine regimens.

Rapid development of diffuse, occlusive coronary artery disease in the cardiac allograft has emerged as a major limiting factor for long-term survival after transplantation. Prior multivariate analyses have failed to identify any strong predictors of this disease. We retrospectively reviewed serial annual coronary angiograms to assess the prevalence of transplant coronary artery disease. A total of 103 patients treated initially with azathioprine-based therapy were compared with a later cohort of 78 patients for whom cyclosporine was the basis of immunosuppressive therapy. The percent of patients free of angiographically visible transplant coronary artery disease at 1 year was 89% for the azathioprine group versus 86% for the cyclosporine group. At 3 years, 74% of the azathioprine group versus 63% of the cyclosporine group were free of visible disease (p = NS). By the fifth postoperative year, 58% of azathioprine-treated and 50% of cyclosporine-treated patients were free of transplant coronary artery disease (p = NS). The mean number of rejection episodes in the first year after transplantation was 2.0 for cyclosporine patients versus 2.5 for azathioprine patients. The azathioprine and cyclosporine patients were compared with respect to a variety of baseline and clinical follow-up measurements that might influence the development of coronary artery disease. Patients in the cyclosporine group had higher blood pressure (135/94 versus 123/85 mm Hg, p less than 0.001) and were receiving lower maintenance prednisone doses. This study demonstrates that improved cyclosporine immunosuppression does not decrease the time-related prevalence of transplant coronary artery disease.

Azathioprine↗

Asynergy of right ventricular wall motion in man.

Canine studies have shown a correlation between instantaneous segmental lengths in the right ventricular free wall and chamber volume, pressure, and stroke work. To determine whether such correlations exist in intact man, we studied the temporal relationships between chord dynamics in various regions of the right ventricle in 21 heart transplant recipients with apparently normal right ventricular function. Patients were examined by biplane radiography while performing various maneuvers (e.g., Valsalva maneuver). Computer-aided analysis of biplane radiograms of five surgically inserted radiopaque tantalum right ventricular myocardial markers was used to calculate interpoint chord lengths at 33 msec sampling intervals. Two patterns of right ventricular chord asynergy were defined: (1) An akinetic chord had an amplitude of less than 2.0 mm during the course of at least one beat; (2) an out-of-phase chord was more than a quarter period out of phase from the average curve (derived from all concurrently measured marker pairs during each maneuver) for at least one beat. Considering all chords (n = 978), 60 chords (6.1%) were akinetic and nine chords (0.9%) were out of phase. Excluding the outflow tract markers (n = 581), 33 chords (5.7%) were akinetic and five chords (0.9%) showed out-of-phase movement. During some maneuver, at least one akinetic chord occurred in 57% of patients and out-of-phase chords in 33% of patients. Most right ventricular regions were implicated in asynergic motion, including the right ventricular free wall, acute margin, and outflow tract. The frequency and distribution of asynergy in right ventricular chord dynamics observed in this study suggests that changes in a single right ventricular dimension may not accurately reflect global right ventricular events.

Electrocardiography↗

Effects of acetylcholine on epicardial coronary arteries after cardiac transplantation without angiographic evidence of fixed graft narrowing.

The coronary response to acetylcholine was evaluated in 10 patients who had had cardiac transplantation 1 to 8 years earlier and in 4 patients who did not undergo transplantation. All 14 patients had no angiographic evidence of fixed coronary arterial narrowing. Acetylcholine was infused in 10-fold increasing concentrations (10(-6) to 10(-2) M) into the midpoint of the left anterior descending coronary artery by an infusion catheter. Administration was terminated when either vasoconstriction was noted at fluoroscopy or when the maximal acetylcholine concentration was reached. Vascular responses were evaluated by quantitative angiography. All 14 patients had a decrease in coronary lumen size in response to acetylcholine. The mean percentage of vasoconstriction was 37 +/- 24% (p less than 0.001). Combined infusion of nifedipine and the maximal vasoconstricting dose of acetylcholine did not result in a significant reversal of coronary vasoconstriction in all 10 cardiac transplantation patients. It was concluded that acetylcholine is a potent coronary vasoconstrictor in patients who had cardiac transplantation and possibly lacks vasodilating effects in most normal patients without angiographic evidence of coronary artery disease, thus suggesting that acetylcholine might not be a suitable pharmacologic agent for testing endothelial cell integrity.

Acetylcholine↗

Sera containing elevated nonesterified fatty acids from patients with angiographically documented coronary atherosclerosis cause marked lipid accumulation in cultured human arterial smooth muscle-derived cells.

Sera from 47 angiography patients were included in medium supporting the growth of human arterial smooth muscle-derived cells (HUSMC). Ten sera from the 38 patients demonstrating significant coronary artery obstruction caused marked cellular accumulation of neutral lipid, causing the cultured cells to resemble the foam cells of atherosclerotic plaque. None of the sera from the 9 non-atherosclerotic patients caused such marked steatosis. A lesser degree of lipid accumulation by the cultured cells was seen for 4/38 atherosclerotic and 2/9 non-atherosclerotic patients sera. The cell lipids were analyzed by thin layer chromatography and were shown to be triglyceride (TG). The quantities of neutral lipids which accumulated in cultured HUSMC were estimated by absorbances due to Oil red O staining of lipid which were normalized to total cell protein based on absorbances due to Coomassie brilliant blue G-250 staining, yielding specific lipid content index values. Serum nonesterified fatty acids (NEFA) concentrations and NEFA/albumin molar ratios were strongly and significantly correlated with specific lipid content index values (r = 0.870, P less than 0.001; r = 0.001, respectively), while total cholesterol and TG concentrations did not yield significant associations. The observed steatosis could be reproduced in HUSMC by the addition of exogenous NEFA to the culture medium. Measurements of proliferation of the cultured HUSMC showed no differences between sera causing lipid accumulation and sera lacking this effect. It is suggested that circulating NEFA concentrations may play a role in the etiology of atherosclerotic plaque.

Arteries↗

Doppler echocardiographic determination of the pressure gradient in hypertrophic cardiomyopathy.

The continuous wave Doppler ultrasound signal across the left ventricular outflow tract in hypertrophic cardiomyopathy has a characteristic pattern that is in keeping with the dynamic nature of the pressure gradient in this condition. To determine the accuracy and reliability of the peak Doppler flow velocity signal for measuring the peak pressure gradient in this condition, 340 beats were analyzed from five consecutive patients studied with simultaneous continuous wave Doppler ultrasound and dual catheter pressure recordings across the left ventricular outflow tract. Each patient was studied at steady state and during physiologic and pharmacologic manipulations of the pressure gradient. Peak velocity and calculated peak gradient were determined by two independent observers who did not know the catheter measurements. In addition, 18 beats with well defined flow velocity envelopes were digitized for analysis of the magnitude, timing and contour of the instantaneous Doppler ultrasound and catheter gradients throughout systole. Peak catheter gradient in the 340 beats ranged from 12 to 245 mm Hg. The correlations between the Doppler-derived and catheter peak gradients were close (r = 0.96, SEE = 4 mm Hg for Observer 1 and r = 0.97, SEE = 11 mm Hg for Observer 2). Interobserver variability for measurement of peak flow velocity was small (mean +/- SD 0.16 +/- 0.15 m/s). An interobserver difference greater than 0.3 m/s occurred in 25 of the 340 beats analyzed. By retrospective analysis, this was due to contamination of the outflow tract signal by mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings.

Annual coronary arteriograms have been obtained from all heart transplant recipients at Stanford University Medical Center since 1969. Angiographic lesions in 81 transplant patients exhibiting coronary vascular disease were classified into three categories: type A, discrete or tubular stenoses; type B, diffuse concentric narrowing; and type C, narrowed irregular vessels with occluded branches. The 81 arteriograms showing transplant coronary vascular disease were contrasted with 32 from nontransplant patients with coronary artery disease analyzed in a similar fashion. The nontransplant angiograms showed 178 lesions, all of type A (discrete or tubular) morphology, 75% of which were located in primary epicardial coronary vessels and 25% in secondary branch vessels. In the patients with transplant coronary vascular disease, 349 (76%) of 461 lesions were type A: 57% in primary vessels, 42% in secondary branches and 1.4% in tertiary branches. Of the 112 type B and C lesions (diffuse narrowing, tapering and obliteration), 25% were in primary vessels, 44% in secondary vessels and 31% in tertiary branches (p less than 0.05 for patients with transplant coronary vascular disease versus patients with nontransplant coronary artery disease). Total vessel occlusion was found in proximal or middle vessel segments in 96% and distally in 4% of patients with "ordinary" coronary artery disease versus 49% distally in patients with transplant coronary disease (p less than 0.002). In the presence of total vessel occlusion, collateral vessels were poor or absent in 92% of transplant versus 7% of nontransplant patients with coronary disease (p less than 0.002). Therefore, coronary artery disease in transplant patients represents a mixture of typical atheromatous lesions and unique transplant-related progressive distal obliterative disease that occurs without collateral vessel development.

Cardiac Catheterization↗

Torsional deformation of the left ventricular midwall in human hearts with intramyocardial markers: regional heterogeneity and sensitivity to the inotropic effects of abrupt rate changes.

The spiral orientation of left ventricular (LV) fibers suggests that twisting about the ventricular long axis of the apex with respect to the base, i.e., torsional deformation, may be characteristic of LV contraction. To demonstrate this twisting motion, 10 orthotopic human cardiac allograft recipients were studied with biplane cineradiography of tantalum helices implanted within the LV midwall at 12 specific sites. Counterclockwise twisting about the LV long axis (as reviewed from apex to base) accompanied ventricular ejection in all patients. Torsional deformation angles, measured relative to a reference minor axis at the base, were substantially smaller in the anteroapical wall, as compared with counterparts in the apical third of the inferior and lateral walls (anterior = 13.3 +/- 6.0 degrees, inferior = 18.7 +/- 6.3 degrees, and lateral = 23.4 +/- 10.7 degrees). Torsional angles at the midventricular level were roughly half as much and exhibited similar regional variabilities (anterior = 7.6 +/- 3.3 degrees, inferior = 9.0 +/- 3.3 degrees, lateral = 10.7 +/- 5.2 degrees, and septal = 8.8 +/- 3.8 degrees). Comparison of control beats and the initial beat after abrupt cessation of rapid atrial pacing (126 +/- 10 beats/min) with return to the control heart rate (96 +/- 9 beats/min) permitted the mild positive inotropic effect of tachycardia to be assessed at similar levels of ventricular load. Torsional deformation of the anteroapical and inferoapical sites increased significantly (p less than 0.05) over control values to 15.6 +/- 7.5 degrees and 21.2 +/- 5.5 degrees, respectively. In contrast, torsional deformation of the lateral wall was essentially unchanged. These data provide direct evidence for torsional deformation of the left ventricle in humans, demonstrate that torsion of the LV chamber is nonuniform, and suggest a dependence of LV torsion upon contractile strength that is attenuated in the lateral wall.

Heart↗

New methodologies for studying the prevention of atherosclerosis.

To determine if multiple risk factor modification favorably alters the rate of progression of coronary atherosclerosis, 300 patients with established atherosclerosis have been randomized into a clinical trial; 155 to usual care and 145 to special intervention. All patients have medical/risk examinations at baseline and annually for 4 years. The special intervention patients undergo aggressive risk factor management with emphasis on lipoprotein modification, dietary management, smoking abatement, blood pressure control, weight loss and increased physical activity. To measure progression of atherosclerosis, a quantitative, computer-assisted coronary arteriographic system was developed to analyze the baseline and 4-year follow-up arteriograms. This procedure uses a catheter with a metallic calibration cylinder at its tip to determine absolute artery size and automated computer edge detection techniques to define the internal border of the artery. The analysis system detects artery borders using changes in cine film density and measures distances between these borders. For each segment the minimum, maximum and mean diameters are measured and percent stenosis and atheroma area calculated. This system provides precise and reproducible measures of coronary artery segment diameter. Using this technique, we estimate a 33% reduction in the rate of coronary artery progression over 4 years, defined as mean segment diameter, can be detected at a power of 0.80 and an alpha of 0.05 (one tailed test) with a sample size of 120 in each of 2 groups.

Coronary Angiography↗

Features of cardiac arrest episodes with and without acute myocardial infarction in the Coronary Artery Surgery Study (CASS).

Angiographic evidence of coronary artery disease was present in 16,002 patients in the Coronary Artery Surgery Study (CASS) registry. Of these patients, 551 had a history of cardiac arrest before enrollment angiography. Cardiac arrest was a complication of acute myocardial infarction (AMI) in 372 patients (68%). Electrocardiographic documentation of the responsible rhythm was available in 283 patients. Ventricular fibrillation (VF) was present in 112 (60%), ventricular tachycardia (VT) in 41 (22%) and both VT and VF in 26 (14%) patients. Stepwise linear discriminant analysis comparing the 551 cardiac arrest patients with the other 15,451 patients selected left ventricular wall motion score (F = 265), use of digitalis (F = 71), impaired blood supply to any segment (F = 16) and particularly to the anterior wall (F = 11) as discriminating variables associated with cardiac arrest. Patients with cardiac arrest occurring as a complication of AMI were younger (F = 12), had greater impairment of coronary blood supply (F = 7) and were more likely to be on a cholesterol-lowering diet (F = 16) than were patients with arrest remote from infarction. Comparison of patients with VT versus those with VF showed a positive association of VT with age (F = 8), a trend toward worse left ventricular function and presence of a left ventricular aneurysm, but no difference in severity and collateralization of coronary artery disease. It is concluded that cardiac arrest is related to the extent of myocardial damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Adaptation of human left ventricular volumes to the onset of supine exercise.

UNLABELLED: The purpose of this study was to measure the changes and rates of adaptation of left ventricular volumes at the onset of exercise. Eight asymptomatic subjects, in whom intramyocardial markers had been implanted 3-6 years previously during aortocoronary bypass surgery, exercised in the supine position at a constant workload of 73.6 W for 5 min. Six also exercised first at 16.4 W, and then against a workload which progressively increased by 8.2 W every 15 s. Cardiac volumes were measured by computer assisted analysis of the motion of the implanted markers. In the constant workload test, cardiac output increased rapidly from 5.7 +/- 1 min-1 to 10.3 +/- 1.9 1 min-1 by 2 min and then increased more slowly to 10.8 +/- 2.0 1 min-1 by 5 min. The cardiac output increase was mainly due to an increase in heart rate from 68 +/- 12 beats min-1 to 120 +/- 16 beats min-1 with minimal changes in stroke volume. The time constant for the early increase in cardiac output was 45s and for heart rate, 35s. With progressively increasing workloads, there was an almost linear increase of heart rate and cardiac output, but these increased at a slower rate than during the early phase of the constant load exercise test. IN CONCLUSION: rapid changes in cardiac output during supine exercise were produced by changes in heart rate; changes in stroke volume provided minor adjustments to cardiac output; the end-diastolic volume was almost constant.

Adaptation, Physiological↗

Bundle branch block in patients with chronic coronary artery disease: angiographic correlates and prognostic significance.

The onset of bundle branch block during acute myocardial infarction is indicative of ischemia in the distribution of the left anterior descending coronary artery. However, whether patients with chronic coronary artery disease and bundle branch block have a predominance of left anterior descending artery lesions is not known. Similarly, the prognostic implications of bundle branch block have been studied primarily in the setting of acute myocardial infarction, and the independent prognostic implications of bundle branch block in patients with chronic coronary artery disease are not known. The electrocardiograms (ECGs) of 15,609 patients with chronic coronary artery disease who underwent coronary and left ventricular angiography as part of the Coronary Artery Surgery Study (CASS) were reviewed, and 522 patients with bundle branch block were identified. Patients with bundle branch block had both more extensive coronary artery disease and worse left ventricular function than did patients without bundle branch block. However, no particular location of coronary artery stenosis or left ventricular wall motion abnormality predominated in patients with bundle branch block. During a follow-up period of 4.9 +/- 1.3 years, 2,386 patients died. Actuarial probability of mortality at 2 years in patients with left bundle branch block was more than five times that in patients without bundle branch block (p less than 0.0001), and in patients with right bundle branch block the mortality rate was approximately twice that in patients without bundle branch block (p less than 0.0001). Stepwise Cox regression analysis showed that left bundle branch block, but not right bundle branch block, was a strong predictor of mortality, independent of degree of heart failure, extent of coronary disease and other variables (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Intraventricular flow during isovolumic relaxation: description and characterization by Doppler echocardiography.

This study describes the characteristics of a prominent Doppler flow velocity signal representing intraventricular flow during left ventricular isovolumic relaxation. The flow during the isovolumic relaxation period was demonstrated in 60 subjects, including 7 with a normal heart, 26 with hypertrophic cardiomyopathy, 10 with aortic valve disease, 9 with a transplanted heart and 8 others. All had normal to hyperdynamic left ventricular systolic function with some degree of cavity obliteration as seen in the apical two-dimensional echocardiographic views. In contrast, this isovolumic relaxation period flow could not be demonstrated in the absence of cavity obliteration in any of 20 patients with either normal or diminished left ventricular systolic function. Isovolumic relaxation period flow was best recorded from the apical transducer position and was directed toward the apex in all patients. By pulsed wave, and with two-dimensional Doppler ultrasound, the isovolumic relaxation period flow originated within a narrow area in the medial portion of the left ventricle along the middle or basal segments of the interventricular septum, but was recorded over a larger area toward the apex. The peak isovolumic relaxation period flow velocity was recorded just basal to the area of cavity obliteration, usually at the level of the papillary muscles, and ranged from 0.4 to 2.3 m/s (mean of 1.0 m/s). This isovolumic relaxation period flow started with aortic valve closure and, in 50 of the 60 patients, it lasted throughout isovolumic relaxation until mitral valve opening. In the other 10 patients (all with hypertrophic cardiomyopathy), it lasted for only a part (mean 63%) of this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗