Time to dP/dt(max), a useful index for evaluation of contractility in the catheterization laboratory.

HYPOTHESIS: The time from onset of contraction to dP/dt(max), td, is suggested as an index of contractility in the catheterization laboratory. METHODS: We studied 22 normal patients and 18 patients with myocardial failure in the catheterization laboratory. The two groups were completely separated on the td-heart rate (HR) plane. In the normal patients, HR = 73 +/- 19 beats/min, td = 73 +/- 11 ms, and an inverse linear relation td = 109-0.49 x HR (p < 0.001) exist. In the patients with myocardial failure, despite significantly higher HR than in normal patients (HR = 93 +/- 14 beats/min) (p < 0.001), td paradoxically increased (td = 89 +/- 11 ms, p < 0.0001). CONCLUSIONS: These findings support a mathematical analysis of the left ventricular pressure (LVP) during isovolumic contraction in the time domain which shows that td and (dP/dt)/P reflect the time-dependent aspects of contraction and, hence, decrease with increasing contractility. This study shows that td, at any given HR, is a reliable index of contractility. Thus, a ready-to-use td-HR plot containing a well-based separation line can provide a reliable and simple method for determining contractility in the catheterization laboratory by examining whether a patient's td value at any HR is below (normal) or above (impaired contractility) the separation line.

Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis.

BACKGROUND: Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction. METHODS AND RESULTS: We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25 +/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P < .05) was accompanied by a significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility. CONCLUSIONS: Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function.

Clinical significance of coronary flow reserve: effect of papaverine and exercise.

BACKGROUND: The clinical significance of coronary flow reserve (CFR) was evaluated after pharmacological (papaverine) and physiological (exercise) vasodilation in patients with coronary artery disease (CAD). METHODS: CFR was determined using parametric imaging in 10 patients with normal coronary arteries (group 1) and in 10 with CAD (group 2). Contrast density and mean appearance time were measured (region of interest = 249 pixels) in the perfusion beds of the left circumflex and the left anterior descending coronary arteries at rest, 45 s after 10 mg intracoronary papaverine, and during supine bicycle exercise. CFR was calculated from coronary perfusion after papaverine divided by perfusion at rest and coronary perfusion during exercise divided by perfusion at rest. Perfusion zones in patients with CAD were subdivided into regions supplied by a non-stenosed (group 2a) and a stenosed (group 2b) coronary artery. RESULTS: In control patients, heart rate increased from 75 beats/min at rest to 125 beats/min during exercise, and in patients with CAD from 63 to 107 beats/min, respectively. Mean aortic pressure showed a significant increase during exercise in both groups. Mean pulmonary artery pressure increased significantly during exercise from 19 to 28 mmHg in control patients and from 22 to 42 mmHg in the CAD group (P < 0.001). Coronary driving pressure (mean aortic minus diastolic pulmonary artery pressure) tended to increase during exercise in the control group (from 90 to 101 mmHg, NS) and remained nearly unchanged in patients with CAD (from 92 to 94 mmHg, NS). In the control group, CFR was significantly higher during exercise than after papaverine (4.0 versus 3.5, respectively; P < 0.01). However, coronary resistance (coronary driving pressure divided by coronary flow index) was similar after papaverine and during exercise. In patients with CAD, papaverine-dependent CFR was significantly reduced in the perfusion zone of the stenosed (2.1) but not of the non-stenosed coronary artery (3.0). In contrast, CFR during exercise was significantly decreased in both perfusion zones (2.5 in non-stenosed arteries and 1.5 in stenosed vessels). CONCLUSIONS: In control patients, CFR is slightly but significantly larger during exercise than after papaverine because of the exercise-induced increase in coronary driving pressure. In contrast, CFR is smaller during exercise than after papaverine in patients with CAD, most probably as a result of secondary mechanisms such as exercise-induced narrowing of stenosed vessels or an increase in extravascular resistance. Thus, CFR based on papaverine appears to be of limited value for assessing the functional significance of a stenotic lesion.

Coronary artery size in mitral regurgitation and its regression after mitral valve surgery.

The relationship between coronary artery size and left ventricular (LV) muscle mass was studied in 10 control subjects and in 10 patients with chronic mitral regurgitation before and 28 +/- 15 months after mitral valve surgery. Left and right coronary artery size was determined by quantitative coronary arteriography. Left coronary artery size was significantly increased before surgery (26 mm2) and decreased after operation (23 mm2), but was still larger than in control subjects (14 mm2). The right coronary artery was also enlarged preoperatively (13 mm2; controls = 9 mm2), but was normalized after surgery (11 mm2). A linear correlation was found between LV muscle mass and left (r = 0.88, p < 0.001) and right coronary artery size (r = 0.84, p < 0.001) as well as between right coronary artery size and mean pulmonary artery pressure (r = 0.56, p < 0.01). Thus in chronic mitral regurgitation the enlargement of the left and right coronary artery is proportional to the degree of LV hypertrophy. The increase in right coronary artery size is probably the result of right ventricular pressure overload. Postoperatively there is only partial regression of left coronary artery size but normalization of right coronary artery size.

Influence of serum cholesterol and other coronary risk factors on vasomotion of angiographically normal coronary arteries.

BACKGROUND: It has been shown that there is impairment of the vasodilatory response to acetylcholine in patients with hypercholesterolemia and angiographically normal coronary arteries. Moreover, in patients with angiographically smooth coronary arteries, the number of coronary risk factors is associated with a loss of endothelium-dependent vasodilation. The purpose of the present analysis was to evaluate in patients with and without coronary artery disease coronary vasomotor response to dynamic exercise in angiographically normal and stenosed coronary arteries and to relate the response to serum cholesterol levels as well as to other coronary risk factors. METHODS AND RESULTS: Luminal area change during exercise (delta-ex, percent change compared with rest = 100%) was determined by biplane quantitative coronary arteriography in three groups: Group 1 consisted of 14 patients with normal total serum cholesterol of < 200 mg/100 mL; mean, 173 mg/100 mL (mean age, 51 years). Group 2 comprised 23 patients with a slightly elevated cholesterol of 200 to 250 mg/100 mL; mean, 223 mg/100 mL (mean age, 53 years). Group 3 had 24 patients with markedly elevated cholesterol of > 250 mg/100 mL; mean, 288 mg/100 mL (mean age, 54 years). Serum cholesterol levels and categorical risk factors such as positive family history, history of hypertension, smoking, obesity, and diabetes were related to exercise-induced vasomotor response. The three groups did not differ with regard to clinical characteristics, exercise work load, and hemodynamic data measured during exercise. However, delta-ex in normal vessels was significantly different between all three groups (ANOVA, P < .01): +31% (group 1), +18% (group 2), and +4% (group 3). Delta-ex in stenotic vessels did not differ between the groups: -5% (group 1), -13% (group 2), and -12% (group 3). Delta-ex of the nonstenosed vessel correlated significantly and inversely with total cholesterol, with low-density lipoprotein cholesterol, with the ratio of total to high-density lipoprotein cholesterol, and with the number of coronary risk factors present in a patient. High total cholesterol and a history of hypertension were independent risk factors for impaired coronary vasomotion. CONCLUSIONS: In patients with and without coronary artery disease, hypercholesterolemia and a history of hypertension independently impair exercise-induced coronary vasodilation in angiographically normal coronary arteries. In the stenotic vessel, vasomotion during exercise does not appear to be influenced by the actual serum cholesterol. The precise mechanism by which the impaired vasomotion of the angiographically normal coronary arteries is mediated is unknown, but a direct negative effect of hypercholesterolemia on endothelial function or early undetected atherosclerosis appears to be the most likely explanation.

Regional left ventricular mechanics in hypertrophic cardiomyopathy.

BACKGROUND: Nonuniformity is a determinant of diastolic function. In patients with hypertrophic cardiomyopathy, hypertrophy, abnormal calcium handling, and regional ischemia can also play a role. This study was designed to assess regional mechanics, asynchrony, and asynergy in patients with hypertrophic cardiomyopathy. METHODS AND RESULTS: Nine control subjects and 22 patients with hypertrophic cardiomyopathy were studied by biplane left ventriculography and high-fidelity pressure tracings for the assessment of diastolic function by computing the time constant of isovolumic relaxation, peak filling rate, and the constant of passive chamber stiffness. Regional mechanics were evaluated by dividing the left ventricle into six sectors in the right and left anterior oblique projections. Systolic and diastolic asynchrony were assessed from the coefficient of variation of the regional time intervals from end diastole to end systole and to peak filling rate, respectively. Asynergy was evaluated from the coefficient of variation of the regional area reduction. Regional passive elastic properties were estimated by computing the regional constant of chamber stiffness. In patients with hypertrophic cardiomyopathy, isovolumic relaxation was prolonged (time constant of isovolumic relaxation 101 +/- 41 versus 51 +/- 16 milliseconds in control subjects; P < .001) and the constant of chamber stiffness was increased (0.056 +/- 0.038 versus 0.025 +/- 0.010 mL-1; P < .001). Both systolic and diastolic asynchrony as well as asynergy were found. Regional mechanics showed hyperkinesia in the free wall, whereas the septum exhibited normal wall motion and increased constant of chamber stiffness. CONCLUSIONS: Diastolic function is impaired in hypertrophic cardiomyopathy, and such an impairment is the consequence of nonuniformity and hypertrophy. The regions where the myopathic process is more pronounced show normal wall motion but increased stiffness. The inhomogeneity of regional wall motion with regional hyperkinesia and normokinesia of neighboring regions results in left ventricular asynergy.

Influence of collagen network on left ventricular systolic and diastolic function in aortic valve disease.

OBJECTIVES: The purpose of this study was to evaluate left ventricular structure-function interplay in aortic valve disease. BACKGROUND: An increase in myocardial fibrosis has been demonstrated in aortic valve disease, but changes in the collagen network and their effect on ventricular function have not been defined. METHODS: Left ventricular structure was assessed from left ventricular endomyocardial biopsy specimens obtained in 32 patients with aortic valve disease (aortic stenosis in 25, aortic regurgitation in 7). Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching), endocardial fibrosis, muscle fiber diameter and volume fraction of myofibrils were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from six donor hearts before transplantation. Eleven other patients with normal left ventricular function served as hemodynamic status control subjects. Left ventricular biplane cineangiography and high fidelity pressure measurements were carried out in all patients. Systolic function was assessed from ejection fraction. Diastolic function was evaluated by the time constant of relaxation, early and late peak filling rates and the constant of passive myocardial stiffness. Patients were assigned to three groups according to increasing severity of nonmyocyte tissue alterations. Group 1 comprised 10 patients with elevated total collagen volume fraction. Group 2 comprised 6 patients with normal total collagen volume fraction and the presence of increased cross-hatching or endocardial fibrosis, or both. Group 3 comprised 16 patients with elevated total collagen volume fraction and the presence of cross-hatching or endocardial fibrosis, or both. RESULTS: Muscle fiber diameter was increased in the three groups with aortic valve disease, whereas the volume fraction of myofibrils was comparable in all four study groups. Ejection fraction was depressed in groups 2 and 3 compared with the control group. The time constant of relaxation was prolonged in the three groups with aortic valve disease. No differences in early and late peak filling rate were observed in the four study groups, but the constant of myocardial stiffness increased in groups 2 and 3. CONCLUSIONS: In aortic valve disease, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered.

Diastolic dysfunction in aortic stenosis.

Diastolic dysfunction is characterized by an increased resistance to filling with increased diastolic filling pressures. A variety of disorders are associated with diastolic dysfunction, such as hypertrophy, structural alterations of the myocardium with increased fibrosis, myocardial scarring, or infiltrative processes. In addition to these changes, physiological abnormalities of the left ventricle with impaired relaxation, decreased diastolic filling, and increased stiffness of the myocardium can be observed. In patients with aortic stenosis, the most common cause for diastolic dysfunction is left ventricular hypertrophy. Diastolic dysfunction is found in approximately 50% of the patients with normal systolic ejection performance and in 100% of the patients with depressed function. Diastolic function appears either to be more sensitive for detection of abnormal left ventricular function in patients with aortic stenosis or to precede systolic dysfunction or both. Treatment of diastolic dysfunction is usually achieved by aortic valve replacement with regression of left ventricular hypertrophy, but in patients with decompensated aortic stenosis, a reduction of circulating blood volume to reduce diastolic filling pressures, and thus dyspnea, is often indicated. Prognosis of patients with diastolic dysfunction is usually better than that of patients with systolic dysfunction but is clearly worse than that of normal patients.

Is atrial pacing needed for determination of coronary flow reserve by parametric imaging?

Heart rate changes during determination of coronary flow by parametric imaging may influence the flow measurement. Thus, the question is whether atrial pacing is mandatory for determination of coronary flow reserve (CFR) by this technique. CFR was calculated by digital subtraction angiography (parametric imaging) in 10 patients (8 with coronary artery disease and 2 control subjects) during sinus rhythm and during atrial pacing. Flow measurements were determined in the perfusion region of the left anterior descending and circumflex coronary artery, both at rest and after maximal coronary vasodilation with 10 mg intracoronary papaverine. CFR was defined as coronary flow during hyperemia divided by coronary flow at rest. Spontaneous heart rate was 71 +/- 15 min-1 at baseline, 73 +/- 15 min-1 after papaverine injection and 85 +/- 10 min-1 during atrial pacing. Heart rate variations during coronary arteriography were 4 +/- 3 min-1 at baseline and 5 +/- 4 min-1 after papaverine administration. CFR was 2.61 +/- 1.01 during sinus rhythm and 2.67 +/- 1.05 during atrial pacing. Mean absolute difference in CFR between sinus rhythm and atrial pacing was 0.31 +/- 0.31 (12 +/- 10% of CFR during pacing). Spontaneous heart rate variations during coronary arteriography are not associated with significant changes in CFR. Thus, atrial pacing is not mandatory for the determination of CFR by parametric imaging.

Evaluation of left ventricular segmental wall motion in hypertrophic cardiomyopathy with myocardial tagging.

BACKGROUND: Segmental wall motion was assessed noninvasively in eight patients with hypertrophic cardiomyopathy and six healthy volunteers by magnetic resonance myocardial tagging. METHODS AND RESULTS: Localization scans were performed for determination of the true short-axis views of the left ventricle (double-angulated view). Spatial modulation of magnetization was used to produce a rectangular grid of landmarks. Distortion of the grid was assessed at end diastole, mid systole, and end systole with multiphase gradient echoes. Image sets were acquired at three different planes, namely, the base, the equator, and the apex. Quantitative evaluation was carried out by computer-assisted image analysis. Each individual grid crossing point was identified automatically and the displacement calculated. A polar coordinate system with the center of gravity as motion reference point was chosen to assess fractional rotation and radial displacement at the endocardial, midwall, and epicardial layers of the septal, anterior, posterior, and inferior regions. A wringing motion of the left ventricle with a clockwise rotation of 5.0 +/- 2.4 degrees at the base and a counterclockwise rotation of -9.6 +/- 2.9 degrees at the apex was observed in control subjects. An equal rotation of 5.0 +/- 2.5 degrees at the base and a slightly reduced rotation of -7.3 +/- 5.2 degrees at the apex was found in patients with hypertrophic cardiomyopathy. A transmural gradient in fractional rotation and radial displacement was observed, with the highest values in the endocardial layer. Rotation in patients with hypertrophic cardiomyopathy was significantly less than in normal volunteers in the posterior region of the equatorial and apical planes. Furthermore, radial displacement was significantly reduced in the septum and inferior wall. In the anterior and posterior wall segments, a reduction of the radial displacement was observed only in the epicardium and midwall layers. CONCLUSIONS: Magnetic resonance myocardial tagging allows the noninvasive assessment of regional wall motion. Both in normal volunteers and in patients with hypertrophic cardiomyopathies, cardiac motion occurs in a complex mode, with the base and the apex rotating in opposite directions and the equatorial plane as a transitional zone (wringing motion). A reduced cardiac rotation can be observed in patients with hypertrophic cardiomyopathy mainly in the posterior region, whereas a reduced radial displacement is found in the inferior septal zone.

Effect of progression of left ventricular hypertrophy on coronary artery dimensions in aortic valve disease.

OBJECTIVES: The effect of progression of left ventricular hypertrophy on coronary artery dimensions was studied in patients with aortic valve disease. METHODS: Cross-sectional area of the left and right coronary arteries was determined by quantitative coronary arteriography in 12 control subjects and in 10 patients with aortic valve disease at baseline and after a follow-up period of 66 months. RESULTS: The cross-sectional area of the left coronary artery was larger in patients with aortic valve disease than in control subjects (left anterior descending artery 13 vs. 8 mm2, p < 0.001; left circumflex artery 13 vs. 6 mm2, p < 0.001). At the follow-up examination, cross-sectional area of the left coronary artery increased (left anterior descending artery 17 mm2, p < 0.01 vs. baseline; left circumflex artery 15 mm2, p < 0.01 vs. baseline). The cross-sectional area of the right coronary artery was not different in patients with aortic valve disease from that in control subjects. Left ventricular muscle mass was larger in patients with aortic valve disease both at baseline (269 g, p < 0.001) and after follow-up examination (339 g, p < 0.001) than in control subjects (136 g). The appropriateness of coronary artery size with respect to muscle mass was evaluated by normalizing cross-sectional area of the left coronary artery (left anterior descending plus left circumflex artery) per 100 g of left ventricular muscle mass (mm2/100 g). This index was 10.9 mm2/100 g in control subjects, and decreased in subjects with aortic valve disease from 10.3 mm2/100 g at baseline to 8.6 mm2/100 g at the follow-up measurement (p < 0.05 vs. control values). CONCLUSIONS: In patients with aortic valve disease, the progression of left ventricular hypertrophy is associated with an increase in left anterior descending and left circumflex coronary artery dimensions, whereas the size of the right coronary artery remains unchanged. Despite the enlargement of the left coronary artery, the cross-sectional area of the left coronary artery per 100 g of left ventricular muscle mass decreased. Hence, the increase in coronary artery size appears to be inadequate when the severity of left ventricular hypertrophy increases.

Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.

OBJECTIVES: The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND: The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS: Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS: Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS: These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.

Coronary tandem lesions: effect of exercise.

Coronary vasomotion of two stenoses in series (i.e., tandem lesion) was studied in 10 patients with coronary artery disease. Percent area stenosis was 69% +/- 23% for the first (S1) lesion and 70% +/- 37% for the second (S2). Quantitative coronary arteriography was carried out at rest, during two levels of exercise (2 minutes, 75 W and 1.9 minutes, 100 W), and at 5 minutes after sublingual administration of 1.6 mg nitroglycerin. Both stenoses showed exercise-induced vasoconstriction (S1: -29%, p less than 0.01 versus rest; S2: -29%, p less than 0.01 versus rest), which was reversible after sublingual administration of nitroglycerin (S1: +15%, not significant versus rest; S2: +13%, not significant versus rest). The vessel segment between the two stenoses showed no vasomotion during exercise, whereas the pre- and poststenotic "normal" vessel segment elicited exercise-induced vasodilation. There was an inverse relationship between percent area stenosis of the second lesion and exercise-induced vasoconstriction of the first lesion (correlation coefficient = 0.84). The more severe the distal stenosis was, the less exercise-induced stenosis narrowing of the proximal lesion was observed. Thus it is concluded that coronary vasomotion of two stenoses in series is dependent on both active and passive mechanisms because both lesions show exercise-induced vasoconstriction, but vasomotion of the proximal lesion is dependent on the severity of the second one.

Fluorescence spectroscopy for identification of atherosclerotic tissue.

OBJECTIVE: Vessel perforation and limited steerability of the laser light are the major limitations of laser angioplasty. To improve steerability fluorescence spectroscopy has been proposed for identification of atherosclerotic plaques. The aim was to investigate this. METHODS: Fluorescence spectroscopy with three different excitation wavelengths (325 nm, 380 nm, 450 nm) was tested in an emission range of 400 nm to 600 nm. Intensity ratios at 480/420 nm were determined in different types of blood vessels. Necropsy material from 40 patients (punch biopsies of 4 mm diameter from the coronary and carotid artery as well as from the ascending and descending aorta) was studied spectroscopically. Histological alterations of the vessel wall were assessed by a semiquantitative score (0 to 10 points): (a) normal tissue, 0 to 2 points (mean = 0.25; n = 38); (b) mild atherosclerotic lesions, 3 to 5 points (mean = 3.35; n = 39); (c) severe atherosclerotic lesions, greater than or equal to 6 points (mean = 6.75; n = 43). RESULTS: Best spectroscopic results were obtained with an excitation wavelength of 325 nm. In samples with severe atherosclerotic lesions the fluorescence spectra showed a significant reduction of the emitted wavelength intensities when compared to normal tissue. There was a clear separation of the fluorescence spectra between normal and mild as well as between normal and severe atherosclerotic lesions; normal tissue showed an increased intensity in the range from 420 nm to 540 nm, whereas atherosclerotic lesions had no or only a small peak at 480 nm. There was a significant correlation between the semiquantitative score (n = 120) and the fluorescence ratio at 480/420 nm (excitation wavelength 325 nm) with a correlation coefficient of 0.87. The spectroscopic results showed no differences between the samples taken from different types of vessels. CONCLUSIONS: Fluorescence spectroscopy allows a reliable identification of normal and atherosclerotic lesions. The close correlation between the emitted light intensity ratio at 480/420 nm and the histological alterations of the vessel wall suggests a relationship between vessel wall fluorescence and the atherosclerotic alterations of the wall.

Hemodynamic performance and myosin light chain-1 expression of the hypertrophied left ventricle in aortic valve disease before and after valve replacement.

Previously, we have reported on the selective accumulation of an atrial-like myosin light chain-1 (ALC1) in different forms of human ventricular hypertrophy. The present study involves the determination of ALC1 content in a control group and in patients with aortic stenosis or insufficiency before and 56 +/- 23 months after valve replacement and compares the hemodynamic and angiographic parameters. ALC1 was quantified densitometrically after two-dimensional electrophoretic resolution of biopsy specimens from the left ventricle and was expressed in percent of total ventricular light chain-1. The mean ALC1 content was 11.2 +/- 9.2% in preoperative aortic stenosis and 4.5 +/- 1.4% in aortic insufficiency, both being significantly (p less than 0.001) higher than the control value of 0.3 +/- 0.3%. After valve replacement, mean ALC1 content was lower than before, 4.2 +/- 3.3% (p less than 0.05) in stenosis and 3.4 +/- 3.1% (p = NS) in insufficiency. Left ventricular systolic pressure yields a significant (p less than 0.01) linear correlation (r = 0.45) with the ALC1 content in all preoperative and postoperative patients. Patient group averages of ALC1 content correlate directly with left ventricular systolic and end-diastolic pressure and wall thickness (r = 0.94-0.98) and, in an exponential fashion, with peak systolic circumferential wall stress (r = 0.98) but not with muscle mass or any other parameter. The ventricular ALC1 binds to myosin in proportion to its occurrence in the myocardium. The content of the endogenous ventricular light chain-1 did not change under pathological hemodynamics. The response in expression of the ALC1 to pressure and volume overload suggests an adaptational process.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of aortic valve stenosis (pressure overload) and regurgitation (volume overload) on left ventricular systolic and diastolic function.

In secondary hypertrophy from chronic pressure or volume overload, or both, systolic as well as diastolic abnormalities of left ventricular (LV) function have been described, but their relation has not been defined. In 58 patients with aortic valve disease (28 with aortic valve stenosis, and 30 with aortic regurgitation) and in 11 control subjects, LV biplane cineangiography was performed simultaneously with LV high-fidelity pressure measurements. LV ejection performance was assessed by ejection fraction, and diastolic function by the time constant of LV pressure decay, the early and late peak filling rates, and the constants of chamber (pressure-volume relation) and myocardial stiffness (stress-strain relation). In the entire cohort (n = 69), ejection fraction was inversely related to the time constant of LV relaxation (r = -0.58, p less than 0.001) and to the constant of myocardial stiffness (r = -0.62, p less than 0.001). Despite preserved systolic contractile function (as evaluated from the ejection fraction-mean systolic stress relation), abnormalities in LV diastolic function were present in 9 of 18 patients with pressure overload and 20 of 22 with volume overload. None of the 58 patients with aortic valve disease had a reduced early peak filling rate, whereas a reduction in late peak filling rate was observed in 3 with aortic stenosis, but in none with aortic regurgitation. This, it appears that abnormalities of relaxation and passive diastolic myocardial stiffness precede alterations in myocardial contractility. Assessment of peak filling rates is not helpful to detect diastolic dysfunction in patients with aortic valve disease.

Regression of coronary artery dimensions after successful aortic valve replacement.

BACKGROUND: The effect of regression of myocardial hypertrophy on coronary artery dimensions was evaluated in patients with aortic valve disease who underwent valve replacement. METHODS AND RESULTS: Cross-sectional area (CSA) of the three major coronary arteries (left anterior descending [LAD], left circumflex [LCx], and right coronary artery) was determined by quantitative coronary arteriography in 15 patients with aortic valve disease before and 38 months (range, 14-113 months) after successful aortic valve replacement. Twelve normal subjects served as controls. Left ventricular (LV) angiographic mass was calculated according to the method of Rackley. CSA of the left coronary artery was larger in aortic valve disease than in controls (LAD, 15 versus 8 mm2, p less than 0.001; LCx, 14 versus 6 mm2, p less than 0.001). After valve replacement, CSA of the left coronary artery decreased (LAD, 12 mm2, p less than 0.05 versus before surgery; LCx, 11 mm2, p less than 0.05 versus before surgery) but remained significantly larger than in controls. CSA of the right coronary artery in patients with aortic valve disease was not different from controls. LV muscle mass was significantly increased in aortic valve disease patients before (364 g) and after (250 g) valve replacement compared with controls (135 g). The appropriateness of coronary artery size with respect to muscle mass was evaluated by normalizing CSA of the left coronary artery (LAD + LCx) per 100 g of LV muscle mass (mm2/100 g). This index amounted to 11 mm2/100 g in controls, to 8 mm2/100 g in preoperative patients (p less than 0.05 versus controls), and to 10 mm2/100 g in postoperative patients with aortic valve disease (p = NS versus controls). CONCLUSIONS: In patients with aortic valve disease, CSA of the proximal LAD and LCx is increased, but this increase is not sufficient to keep CSA per 100 g of LV mass within normal limits. The postoperative decrease in muscle mass is associated with a decrease in the size of LAD and LCx, whereas the size of the right coronary artery remains unchanged. In contrast to the preoperative state, the residually hypertrophied LV myocardium after aortic valve replacement is supplied by an enlarged but adequately sized LAD and LCx.

Acquisition and evaluation of tagged magnetic resonance images of the human left ventricle.

Magnetic resonance myocardial tagging was used to noninvasively analyze the complicated contraction pattern of the human cardiac left ventricle. The tagging and imaging sequence was optimized to obtain three to four double-angulated short-axis views during systole. The image contrast between labeled and unlabeled tissue was sufficient to apply a semiautomatic image evaluation procedure. In accordance with the invasively achieved findings of other groups, the measurements indicate a wringing motion of the left ventricle, with a clockwise twist at the heartbase and a contrary rotation at the apical level.

Myocardial oxygen consumption in aortic valve disease with and without left ventricular dysfunction.

OBJECTIVE: To assess whether and to what extent myocardial oxygen consumption is modified by hypertrophy and alterations in contractility in patients with aortic valve disease and to evaluate the influence of regression of left ventricular hypertrophy and improvement of contractility on myocardial oxygen consumption after successful aortic valve replacement. DESIGN: A cohort analytical study to investigate the influence of the "explanatory" variables of myocardial oxygen consumption by multiple regression analysis. A comparison of myocardial oxygen consumption in preoperative patients with that after operation in a group with comparable severity of aortic valve disease before operation (analysis of covariance). PATIENTS: In six controls and in 43 patients with aortic valve disease and normal coronary arteries standard haemodynamic variables were measured, left ventricular biplane cineangiography performed, and coronary sinus blood flow measured by thermodilution. The patients were divided into three groups: 19 preoperative patients with normal ejection fraction (greater than or equal to 57%) (group 1); nine preoperative patients with reduced ejection fraction (less than 57%) (group 2); 16 postoperative patients (one with preoperative and postoperative measurements (group 3). Postoperative evaluation was performed 12-51 months after surgery. MAIN OUTCOME MEASUREMENTS: Myocardial oxygen consumption/100 g left ventricular muscle mass and its suspected "explanatory" variables--that is, peak systolic left ventricular circumferential wall stress, heart rate, contractility (assessed by left ventricular ejection fraction), and left ventricular muscle mass index. RESULTS: Multiple regression analysis showed that the product of peak systolic stress and heart rate (p less than 0.0001) and ejection fraction (p less than 0.03) were positively correlated with myocardial oxygen consumption/100 g and that left ventricular muscle mass index (p less than 0.002) was negatively correlated with myocardial oxygen consumption/100 g (r = 0.72; n = 50 measurements). Myocardial oxygen consumption per 100 g at a given stress-rate product was higher in the controls than in group 1 (hypertrophied ventricles with normal ejection fraction) and was also higher in group 1 than in group 2 (hypertrophied ventricles with reduced ejection fraction). In a subgroup of the postoperative patients with complete regression of hypertrophy and normalisation of contractility, myocardial oxygen consumption per 100 g at a given stress-rate product was indistinguishable from that in controls. CONCLUSIONS: When the actual stress-rate product was used as an index of overall left ventricular performance the results suggested that mechanical efficiency was increased in hypertrophied ventricles especially when contractility was decreased. These changes in mechanical efficiency seemed to be reversible during the postoperative course when muscle mass and contractility returned to normal.