Theodore Plappert

Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril.

BACKGROUND Left ventricular enlargement after myocardial infarction increases the likelihood of an adverse outcome. In an echocardiographic substudy of the Survival and Ventricular Enlargement (SAVE) Trial, we assessed whether captopril would attenuate progressive left ventricular enlargement in patients with left ventricular dysfunction after acute myocardial infarction and, if so, whether this would be associated with improved clinical outcome. METHODS AND RESULTS Two-dimensional transthoracic echocardiograms were obtained in 512 patients at a mean of 11.1 +/- 3.2 days after infarction and were repeated at 1 year in 420 survivors. Left ventricular size was assessed as left ventricular cavity areas at end diastole and end systole and left ventricular function as percent change in cavity area from end diastole to end systole. Patients were randomly assigned to placebo or captopril, and the incidence of adverse cardiovascular events consisting of cardiovascular death, heart failure requiring either hospitalization or open-label angiotensin-converting enzyme inhibitor therapy, and recurrent infarction were determined over a follow-up period averaging 3.0 +/- 0.6 years. Irrespective of treatment assignment, baseline left ventricular systolic area and percent change in area were strong predictors of cardiovascular mortality and adverse cardiovascular events. At 1 year, left ventricular end-diastolic and end-systolic areas were larger in the placebo than in the captopril group (P = .038, P = .015, respectively), and percent change in cavity area was greater in the captopril group (P = .005). One hundred eleven of the 420 1-year survivors with 1-year echo measurements (26.4%) experienced a major adverse cardiovascular event, and these patients had more than a threefold greater increase in left ventricular cavity areas than those with an uncomplicated course. Sixty-nine patients with adverse cardiovascular events were in the placebo group compared with 42 patients in the captopril-treated group (a risk reduction of 35%, P = .010). CONCLUSIONS Two-dimensional echocardiography provides important and independent prognostic information in patients after infarction. Left ventricular enlargement and function after infarction are associated with the development of adverse cardiac events. Attenuation of ventricular enlargement with captopril in these patients was associated with a reduction in adverse events. This study demonstrates the linkage between attenuation of left ventricular enlargement by captopril after infarction and improved clinical outcome.

Noninvasive determination of left ventricular end-systolic stress: validation of the method and initial application.

End-systolic left ventricular (LV) meridional wall stress is a quantitative index of true myocardial afterload that can be plotted against LV end-systolic diameter to give an index of contractility independent of loading conditions. We developed a noninvasive method for estimating end-systolic LV meridional wall stress based on M-mode LV echographic end-systolic diameter (LVID) and posterior wall thickness (PWT) and cuff systolic arterial pressure and compared it to simultaneous invasive LV wall stress derived from micromanometer LV pressure recordings and continuously digitized echograms in 12 subjects (four with atypical chest pain, six with severe aortic regurgitation (AR) and two with congestive cardiomyopathy), before and after load manipulation with nitroprusside, nitroglycerin, phenylephrine or saline. Cuff systolic pressure correlated well with end-systolic LV micromanometer pressure (r = 0.89, n = 31, range 96-160 mm Hg) and noninvasive end-systolic stress (0.334 P(LVID)/PWT [1 + PWT/LVID]) correlated extremely well with invasive stress (r = 0.97, n = 31, range 36-213 × 109 dyn/cm2). Invasive and noninvasive slopes (r = 0.91, n = 7) and LVID intercepts (r 0.89, n = 7) of the stress-diameter plots also correlated well. Noninvasive stressdiameter plots in nine normal subjects showed a range of slopes of 50-93 × 101 dyn/cm and intercepts of 1.8-2.8 cm. Mean basal end-systolic noninvasive stress in 22 normal subjects (64.8 ± 19.5 × 10W dyn/cm2) and 14 treated hypertensives (56.3 ± 26.7 × 103 dyn/cm2) was significantly lower than in nine patients with symptomatic aortic regurgitation who had reduced ejection fraction (142.2 ± 53.2 × 10° dyn/cm2, p < 0.01) or four patients with congestive cardiomyopathy (187.3 ± 49.8 × 103 dyn/cm2, p < 0.01), while a mild elevation of stress in symptomatic aortic regurgitation with normal ejection fraction was not statistically significant (91.1 ± 20.7 × 103 dyn/cm2, n = 6). Thus, afterload excess contributed to ejection fraction reduction. We conclude that end-systolic stress may be determined noninvasively and may be a useful approach to quantitation of LV afterload and contractility.

Effect of Annular Shape on Leaflet Curvature in Reducing Mitral Leaflet Stress

Background—Leaflet curvature is known to reduce mechanical stress. There are 2 major components that contribute to this curvature. Leaflet billowing introduces the most obvious form of leaflet curvature. The saddle shape of the mitral annulus imparts a more subtle form of leaflet curvature. This study explores the relative contributions of leaflet billowing and annular shape on leaflet curvature and stress distribution. Methods and Results—Both numerical simulation and experimental data were used. The simulation consisted of an array of numerically generated mitral annular phantoms encompassing flat to markedly saddle-shaped annular heights. Highest peak leaflet stresses occurred for the flat annulus. As saddle height increased, peak stresses decreased. The minimum peak leaflet stress occurred at an annular height to commissural width ratio of 15% to 25%. The second phase involved data acquisition for the annulus from 3 humans by 3D echocardiography, 3 sheep by sonomicrometry array localization, 2 sheep by 3D echocardiography, and 2 baboons by 3D echocardiography. All 3 species imaged had annuli of a similar shape, with an annular height to commissural width ratio of 10% to 15%. Conclusion—The saddle shape of the mitral annulus confers a mechanical advantage to the leaflets by adding curvature. This may be valuable when leaflet curvature becomes reduced due to diminished leaflet billowing caused by annular dilatation. The fact that the saddle shape is conserved across mammalian species provides indirect evidence of the advantages it confers. This analysis of mitral annular contour may prove applicable in developing the next generation of mitral annular prostheses.

Anatomic validation of left ventricular mass estimates from clinical two-dimensional echocardiography: initial results.

We performed a prospective anatomic validation study to determine the accuracy of left ventricular (LV) mass estimates from clinical two-dimensional echocardiographic (2-D echo) studies. In 21 subjects, antemortem 2-D echo LV mass determinations were compared with anatomic LV weight by postmortem chamber dissection. Major cardiac diagnoses included anatomic LV aneurysm in four, status post aneurysmectomy in one, transmural myocardial infarction in seven, congestive cardiomyopathy in five, rheumatic mitral disease in two, chronic severe mitral or aortic regurgitation in three, amyloid heart in two, and normal heart in three. Marked right-heart dilatation was present in 11 patients and LV thrombus in four. Regression equations derived in vitro for each 2-D echo instrument were used to correct LV mass estimates based on a short-axis, area-length method: uncorrected LV mass = 1.055 x k x 5/6 (AtLt - ACLC) + b, where At = total short-axis LV image area at the high papillary muscle level, Lc = endocardial LV length, k = an instrument-specific regression slope and b = an instrument-specific intercept. LV mass by 2-D echo correlated extremely well with actual LV weight (r = 0.93 slope = 0.85, SEE 31 g, range 77–454 g). In contrast, M-mode echocardiographic LV mass estimates were less reliable (r = 0.86, SEE = 59 g) in these markedly distorted hearts. These 2-D echo LV mass results compare favorably with reported results from biplane angiography and M-mode echocardiography in more symmetric hearts. Thus, regression-corrected 2-D echo be the method of choice for determining LV mass in man.

Changes in intracardiac blood flow velocities and right and left ventricular stroke volumes with gestational age in the normal human fetus: a prospective Doppler echocardiographic study.

We used Doppler echocardiography to quantitate the changes in intracardiac blood flow velocities and right and left ventricular stroke volumes in 80 normal human fetuses from 19 to 40 weeks gestation. Blood flow velocity spectra across the aortic, pulmonary, tricuspid, and mitral valves were digitized to obtain peak velocities (m/sec) and flow velocity integrals. Aortic and pulmonary diameters were measured at valve level from two-dimensional echocardiographic images and cross-sectional area was calculated assuming a circular orifice. Ventricular stroke volume was calculated as the product of the cross-sectional area of a great vessel and the flow velocity integral through that vessel. The pulmonary arterial and aortic diameters increased linearly with gestational age (r = .82, r = .84), and pulmonary arterial diameter consistently exceeded aortic diameter. There was a positive relationship between stroke volume and gestational age: stroke volume increased exponentially from 0.7 ml at 20 weeks to 7.6 ml at 40 weeks for the right ventricle (r = .87) and from 0.7 ml at 20 weeks to 5.2 ml at 40 weeks for the left ventricle (r = .91). Similar results were obtained for right and left ventricular and combined cardiac outputs. In 44% of the fetuses it was possible to quantitate both right and left ventricular stroke volumes. There was a close correlation between right and left ventricular stroke volumes in these fetuses (r = .96) and right ventricular stroke volume exceeded left ventricular stroke volume by 28%.(ABSTRACT TRUNCATED AT 250 WORDS)

Early postoperative changes in left ventricular chamber size, architecture, and function in aortic stenosis and aortic regurgitation and their relation to intraoperative changes in afterload: a prospective two-dimensional echocardiographic study.

We prospectively studied 16 patients with isolated aortic stenosis and eight with isolated aortic regurgitation undergoing aortic valve replacement, using two-dimensional echocardiography preoperatively, intraoperatively, and 41 +/- 7 days postoperatively to calculate the intraoperative change in afterload, quantify the postoperative changes in left ventricular chamber size, architecture, load and function, determine whether the postoperative left ventricular remodeling correlated with the intraoperative change in afterload in aortic stenosis and aortic regurgitation, and assess whether preoperative afterload excess precluded postoperative improvement in left ventricular function. Preoperative left ventricular mass, end-systolic meridional and circumferential wall stresses, ejection fraction, and stress-shortening relations in patients with aortic stenosis and aortic regurgitation were similar. However, our patients with aortic regurgitation had severe systolic dysfunction, with ejection fraction less than 55% in all but one patient, compared with only 10 of 16 patients with aortic stenosis. Left ventricular end-diastolic volume, mass/volume ratio, and chamber shape were significantly different in patients with aortic stenosis and aortic regurgitation (174 +/- 64 vs 294 +/- 140 ml, p less than .01; 1.81 +/- 0.63 vs 1.14 +/- 0.18, p less than .01; and 0.59 +/- 0.09 vs 0.69 +/- 0.09, p less than .05, respectively). Intraoperative end-systolic meridional and circumferential stresses fell significantly in patients with aortic stenosis but remained unchanged in those with aortic regurgitation. The changes in left ventricular volume and ejection fraction during early postoperative remodeling (6 weeks) correlated with the intraoperative change in afterload in patients with aortic stenosis. In contrast, there was no intraoperative change in afterload in patients with aortic regurgitation and no significant changes in left ventricular volume, architecture, or function at 6 weeks or at 6 months. The differences in left ventricular remodeling and changes in function between patients with aortic stenosis and aortic regurgitation in the early postoperative period most probably relates to the major difference in intraoperative reduction in afterload, although a contributory role may have been played by the preoperative left ventricular dysfunction in those with aortic regurgitation that was underestimated by measurement of ejection fraction.

Infarct size and location determine development of mitral regurgitation in the sheep model.

OBJECTIVE This study tests the hypothesis that neither small nor large myocardial infarctions that include the anterior papillary muscle produce mitral regurgitation in sheep. METHODS Coronary arterial anatomy to the anterior left ventricle and papillary muscle was determined by dye injection in 41 sheep hearts and by triphenyl tetrazolium chloride in 13. Development of acute or chronic mitral regurgitation and changes in left ventricular dimensions were studied by use of transdiaphragmatic echocardiography in 21 sheep after infarction of 24% and 33% of the anterior left ventricular mass. These data were compared with previous data from large and small posterior left ventricular infarctions. RESULTS Ligation of two diagonal arteries infarcts 24% of the left ventricular mass and 82% of the anterior papillary muscle. Ligation of both diagonals and the first circumflex branch infarcts 33% of the left ventricle and all of the anterior papillary muscle. Neither infarction causes mitral regurgitation, although left ventricular cavity dimensions increase significantly at end systole. After the smaller infarction, the left ventricular cavity enlarges 150% over 8 weeks without mitral regurgitation. CONCLUSIONS In sheep small and large infarctions of the anterior wall that include the anterior papillary muscle do not produce either acute or chronic mitral regurgitation despite left ventricular dilatation. In contrast large posterior infarctions produce immediate mitral regurgitation owing to asymmetric annular dilatation and discoordination of papillary muscle relationships to the valve. After small posterior infarctions that include the posterior papillary muscle, mitral regurgitation develops because of annular and ventricular dilatation during remodeling.

Comparison of echocardiography methods for assessment of left ventricular shortening and wall stress

M-mode echocardiographic measurement of left ventricular fractional shortening and meridional wall stress has been used extensively alone and in combination to describe left ventricular systolic function. To determine whether the improved dimensional information afforded by two-dimensional echocardiography might result in shortening and stress calculations yielding a different view of left ventricular function, we compared two-dimensional and M-mode echocardiograms in 69 subjects (19 normal, 13 with aortic stenosis, 22 with aortic regurgitation and 15 with congestive cardiomyopathy). Fractional shortening was greater with M-mode than with two-dimensional echocardiography in all subjects, especially in those with cardiomyopathy (p less than 0.05). In aortic stenosis, two-dimensional shortening, at 24 +/- 5%, was reduced (p less than 0.05 versus normal), but M-mode shortening, at 34 +/- 5%, was not. M-mode estimates of meridional stress were higher than two-dimensional values, again especially in cardiomyopathy. Two-dimensional echocardiography enabled determination of long- and short-axis ratios, circumferential stress and the ratio of circumferential to meridional stresses. Circumferential stress was elevated in aortic stenosis at 302 +/- 65 X 10(3) dynes/cm2, suggesting afterload excess as the cause for the observed reduction in two-dimensional shortening. The more spherical cardiomyopathic hearts had a meridional to circumferential stress ratio closer to 1, such that use of meridional stress alone would overestimate effective afterload. It is concluded that M-mode and two-dimensional echocardiographic analyses of left ventricular shortening and stress produce different results. Two-dimensional echocardiographic methods may enhance the assessment of ventricular function, especially in patients with aortic stenosis and cardiomyopathy.

Effects of heart rate on ventricular size, stroke volume, and output in the normal human fetus: a prospective Doppler echocardiographic study.

The effect of heart rate on cardiac output in the fetal heart is controversial. We used Doppler echocardiography to investigate the effects of increasing heart rate on stroke volume and ventricular output in the normal human fetal heart. Heart rate was increased in 25 human fetuses (mean age 36 weeks) by auditory stimulation with a sound emitter placed on the mothers abdomen. Aortic or pulmonary diameters were measured at valve level from two-dimensional echocardiographic images and cross-sectional areas were calculated. Blood flow velocity spectra from the pulmonary artery or aorta were digitized to obtain flow velocity integrals before and after auditory stimulation. Stroke volume was calculated as the product of the flow velocity integral and the area of the great vessel. Prestimulation mean heart rate was 132 +/- 8 beats/min and increased after auditory stimulation to 158 +/- 9 beats/min (p less than .001). Stroke volume decreased with the increase in heart rate from 3.7 +/- 1.4 ml before stimulation to 3.0 +/- 1.1 ml after stimulation (p less than .001), but ventricular output calculated as the product of stroke volume and heart rate remained unchanged (0.48 +/- 0.18 liter/min before vs 0.48 +/- 0.17 liter/min after stimulation). The decrease in stroke volume was accompanied by a decrease in ventricular end-diastolic area, although there was no change either in end-systolic area or fractional change in area. This study demonstrates that increases in heart rate within the physiologic range in the normal human fetus result in a decrease in ventricular size and stroke volume but no change in ventricular output or ventricular shortening.

Distortions of the Mitral Valve in Acute Ischemic Mitral Regurgitation

BACKGROUND In the absence of papillary muscle rupture, the precise deformations that cause acute postinfarction mitral valve regurgitation are not understood and impair reparative efforts. METHODS In 6 Dorsett hybrid sheep, sonomicrometry transducers were placed around the mitral annulus (n = 6) and at the tips and bases of both papillary muscles (n = 4). Later, specific circumflex coronary arteries were occluded to infarct approximately 32% of the posterior left ventricle and produce acute 2 to 3+ mitral regurgitation. Before and after infarction, distance measurements between sonomicrometry transducers produced three-dimensional coordinates of each transducer every 5 ms. RESULTS After infarction, the annulus dilated asymmetrically orthogonal to the line of leaflet coaptation, but the annular area increased only 9.2% +/- 6.3% (p = 0.02). At end-systole, posterior papillary muscle length increased 2.3 +/- 0.9 mm (p = 0.005); the posterior papillary muscle tip moved closer to the annular plane and centroid, and the anterior papillary muscle tip moved away. CONCLUSIONS Small deformations in mitral valvular spatial geometry after large posterior infarctions are sufficient to produce moderate to severe mitral regurgitation. The most important changes are asymmetric annular dilatation, prolapse of leaflet tissue tethered by the posterior papillary muscle, and restriction of leaflet tissue attached to the anterior papillary muscle.