M G St John Sutton

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.

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)

Quantitative assessment of growth and function of the cardiac chambers in the normal human fetus: a prospective longitudinal echocardiographic study.

We assessed the changes in cardiac chamber size, architecture and function in the normal fetus in a prospective, longitudinal, two-dimensional, and two-dimensionally directed M mode echocardiographic study. Serial echocardiograms were recorded in 16 normal fetuses at 4 week intervals from 20 weeks gestation to parturition. Fetal gestational age was assessed by biparietal diameter. Left ventricular, right ventricular, and left atrial chamber sizes and aortic diameter all increased linearly with age. The ratios of right and left ventricular diameter, left atrial to aortic diameters, and relative left ventricular wall thickness that we used as an index of short-axis left ventricular architecture remained constant. Fractional right ventricular and left ventricular wall thicknesses were similar both on echocardiograms and in postmortem hearts over the same range of gestational ages. In addition, postmortem right ventricular and left ventricular free wall weights were indistinguishable and contributed the same proportion to total heart weight throughout gestation. Left ventricular echocardiographic mass increased linearly from a mean of 0.86 +/- 0.09 to 7.47 +/- 2.43 g at term and corresponded closely with postmortem left ventricular weight. We conclude that (1) fetal cardiac chamber dimensions, wall thicknesses, and left ventricular mass increased with gestational age, (2) cardiac architecture in terms of the ratios of right ventricular/left ventricular diameters, left atrial/aortic diameters, and relative wall thickness remained constant, (3) right and left ventricular fractional shortening did not change with age, (4) left ventricular mass assessed echocardiographically corresponded closely with postmortem left ventricular weights in fetal hearts of similar gestational ages, and (5) the similarities between right and left ventricular sizes, wall thicknesses, and free wall weights in this study do not support the theory of right ventricular dominance in the human fetus.

Diagnosis in adolescents and adults with congenital heart disease. Prospective assessment of individual and combined roles of magnetic resonance imaging and transesophageal echocardiography.

BackgroundThe inability to obtain complete diagnoses with transthoracic echocardiography in many adults with congenital heart disease provided the incentive to evaluate prospectively the individual and combined roles of magnetic resonance imaging (MRI) and transesophageal echocardiography (TEE) as “second-line” techniques for unresolved diagnostic problems. Methods and ResultsEighty-five patients were studied; 81 had MRI with a 0.5-T magnet to obtain spin- echo images, cine-MRI, and flow-velocity maps. Seventy-nine patients had TEE (37 biplane). A simple score (range, 0 to 1) was used for quantification of the results of MRI and TEE alone, for their comparison (in the 75 patients who had both), and for assessment of their combination. MRI, TEE, or their combination achieved a score of at least 0.75 in 18 of 25 diagnostic categories. A summary of the scores showed that for intracardiac anatomy. MRI scored 0.34, TEE scored 0.71 (P < .0001), and MRI plus TEE scored 0.84 (P < .003); for extracardiac anatomy, MRI scored 0.76, TEE scored 0.23 (P < .0001), and MRI plus TEE scored 0.84 (P = NS); and for hemodynamics and function, MRI scored 0.58, TEE scored 0.41 (P < .05), and MRI plus TEE scored 0.67 (P = NS). Total scores were MRI, 0.52; TEE, 0.50 (P = NS); and MRI plus TEE, 0.80 (P < .0001). MRI and TEE were inadequate for collateral and coronary arteries and pulmonary vascular resistance. Cine-MRI and flow-velocity maps comprised 43% of the MRI scores. Biplane TEE was better than single plane (scores of 0.59 versus 0.42, P < .0001). ConclusionsMRI and TEE are important and complementary “second-line” investigations for congenital heart disease. Analysis of their performance in a wide range of diagnostic categories provides guidelines for their judicious application. Where both are available, diagnostic catheterizations are either obviated or simplified.

Effects of reduced left ventricular mass on chamber architecture, load, and function: a study of anorexia nervosa.

We investigated the effects of reduction in left ventricular mass on cavity geometry, afterload, pump function, and exercise performance in 17 patients with anorexia nervosa and in 10 age-and sex-matched normal subjects. Left ventricular mass index determined by two-dimensional echo-cardiography was significantly lower than that in normal subjects (53 +/- 15 vs 79 +/- 18 g/m2; p less than .005). Left ventricular end-diastolic and end-systolic volume indexes were also reduced in patients with anorexia nervosa compared with normal subjects (49 +/- 11 vs 65 +/- 17 ml/m2, p less than .005; 14 +/- 5 vs 19 +/- 4 ml/m2, p less than .025). In spite of the reductions in left ventricular mass and volume indexes, left ventricular chamber architecture described as h/R ratio, mass to volume ratio, and short/long left ventricular axis ratio were normal. Left ventricular afterload assessed as end-systolic meridional and circumferential wall stress was normal (59 +/- 18 vs 79 +/- 19 dyne/cm2 X 10(3) and 170 +/- 26 vs 167 +/- 23 dyne/cm2 X 10(3)). Ejection fraction, percent fractional shortening, and the relationship between end-systolic wall stress and ejection fraction were all within normal limits. In seven patients restudied after a 15% to 20% weight gain, left ventricular mass and volume indexes increased significantly but end-systolic wall stress and ejection fraction did not change. Ten patients with anorexia nervosa and resting heart rates and systolic blood pressures significantly lower than control values underwent treadmill testing. Exercise duration, peak heart rate, peak systolic blood pressure, and peak oxygen consumption in these patients were all significantly lower than normal. The hypotensive effect of fasting resulted in an initial decrease in afterload, which was the stimulus for reduction in left ventricular mass. The left ventricular remodeling associated with the mass reduction occurred in such a way that (1) orthogonal, meridional, and circumferential wall stresses were normalized, (2) normal chamber shape and architecture were maintained, and (3) chamber function and stress-shortening relationships were preserved. Thus down-regulation of left ventricular mass per se, like up-regulation of left ventricular mass, is not associated with abnormal left ventricular function.

Computerized M-mode echocardiographic analysis of left ventricular dysfunction in cardiac amyloid.

We assessed left ventricular (LV) function in cardiac amyloid using computer-assisted analisis of M-mode echocardiograms from 20 patients with biopsy-proved amyloid and compared them with similar data from 20 normal subjects. Patients with cardiac amyloid had a consistent and characteristic set of quantitative echocardiographic findings: (1) LV cavitv size was normal or small. (2) The peak rate of diastolic cavity filling was decreased (p < 0.01). (3) Isovolumic relaxation was prolonged (p < 0.01). (4) Fractional shortening and peak Vcf were decreased (p < 0.01). (5) Peak rates of both systolic thickening and diastolic thinning of the septum and posterior LV wall were decreased (p < 0.01). LV function in patients with cardiac amyloid was compared with that in patients with aortic stenosis and normal coronary arteries, who were used as a model of similar wall thickness and cavitx size. There was significantly greater impairment of regional and global LV function in amyloid, that is, more than could be accounted for by increased wall thickness alone, indicating that the further abnormalities of LV function were caused by an intramyocardial restriction secondary to amyloid deposition per se. LV function was also compared in amyloid and in patients with nonobstructive hypertrophic cardiomvopathv, as these two groups of patients may be confused both clinically and echocardiographically. The technique we used differentiated between these two disorders in terms of cavity and regional LV dynamics when patients were considered as a group, but with less certaintv when patients were considered individuallv due to overlap between the two groups. The severity and consistency of the echocardiographic abnormalities in cardiac amyloid are of value in establishing the diagnosis, which can be confirmed directlv bv tissue biopsv.

Assessment of left ventricular mechanics in patients with asymptomatic aortic regurgitation: a two-dimensional echocardiographic study.

We describe a noninvasive method for determining end-systolic meridional and circumferential wall stress and left ventricular architecture as the ratio of muscle to cavity area. With this technique, which uses two-dimensional echocardiography and cuff-determined values for systolic blood pressure, we assessed wall stress and left ventricular architecture in 15 normal subjects and 15 asymptomatic patients with severe chronic aortic regurgitation at rest and after load manipulations with sublingual nitroglycerin. Resting end-systolic meridional and circumferential stress were increased in patients with aortic regurgitation (113.9 +/- 29 and 260 +/- 50.7 X 10(3) dynes/cm2) compared with those in normal subjects (85.6 +/- 15.4 and 214.1 +/- 28.4 X 10(3) dynes/cm2) (both p less than .01) and remained significantly greater after nitroglycerin. Meridional stress values obtained from two-dimensional echocardiographic studies correlated closely (r = .89) with values calculated from simultaneously recorded M mode echocardiograms. Ejection fraction in patients with aortic regurgitation and normal subjects were similar at rest (55 +/- 10% vs 59 +/- 6%) and were unchanged by nitroglycerin. In spite of the increased left ventricular mass in patients with aortic regurgitation (227 +/- 60 g vs 130 +/- 22 g in normal subjects), the mass-to-volume ratio and the ratio of muscle to cavity area in diastole in patients with aortic regurgitation were significantly lower than normal (0.90 +/- 0.23 vs 1.30 +/- 0.21 and 0.91 +/- 0.23 vs 1.11 +/- 0.18 [p less than .005 and p less than .02]). These differences were exaggerated after nitroglycerin, while concomitant changes in relative wall thickness were virtually undetected by M mode echocardiography. Thus this technique can be used for early recognition of afterload excess and changes in left ventricular architecture in patients with aortic regurgitation. Furthermore, the mean slopes of the circumferential stress-diameter and meridional stress-length lines, which represent load-independent indexes of myocardial contractile state, could be assessed and were similar in the group of patients with asymptomatic aortic regurgitation and normal subjects, indicating that overall myocardial contractility was still normal. We conclude that circumferential and meridional wall stress, myocardial contractility, and left ventricular architecture can be determined noninvasively. These measurements may prove to be useful in assessing patients with primary myocardial or valvular heart disease and determining their long-term management.

Assessment of left ventricular function in secundum atrial septal defect by computer analysis of the M-mode echocardiogram.

Left ventricular function in 53 patients with secundum atrial septal defect was assessed by computer-assisted analysis of the left ventricular echocardiogram and by cardiac catheterization. The patients were divided into two groups, those younger and those older than 60 years, to investigate the effect of aging on left ventricular function. Cavity size was significantly smaller than normal (P < 0.01) and septal motion was abnormal in 86%, but values for cardiac index, left ventricular end-diastolic pressure, velocity of circumferential fiber shortening, left ventricular filling rate, and duration of rapid filling were normal in both groups. Regional dynamics assessed in terms of peak rates of systolic thickening and diastolic thinning of the septum and posterior wall were also normal in both groups. We concluded that, although left ventricular minor dimensions are small, and septal motion is reversed in the majority of patients with atrial septal defect, left ventricular function is normal, and it does not appear to deteriorate with increased age, pulmonary hypertension, or the presence of right ventricular failure. The abnormal septal motion appears to be compensated for by enhanced septal and posterior wall percentage thickening.

Quantitative assessment of right and left ventricular growth in the human fetal heart: a pathoanatomic study.

We quantitated the growth patterns of the normal fetal heart and the right and left ventricles from postmortem hearts obtained from 55 spontaneously aborted human fetuses from the completion of cardiogenesis to term. Fetal gestational age was assessed by menstrual history of the mother, crown-rump length, head circumference, and body weight and ranged from 8 to 40 weeks. Each heart was perfused and fixed at constant pressure and dissected to obtain right and left ventricular free wall, left ventricular, and total heart weights. Right and left ventricular free wall thicknesses were measured and the respective surface areas were calculated. The changes in each of these parameters with gestational age were examined by regression analysis. Total heart and right and left ventricular wall weights increased linearly with body weight, but exponentially with head circumference, crown-rump length, and menstrual history. Right and left ventricular free wall weights were similar throughout gestation and the percent that each contributed to total heart weight were constant at 29 +/- 2% and 30 +/- 2%, respectively. Right and left ventricular wall thicknesses did not differ significantly, increasing linearly with menstrual age, crown-rump length, head circumference, and body weight from 8 to 40 weeks. The surface areas of the right and left ventricular free walls that we used as an index of changing ventricular architecture were indistinguishable throughout the period of gestation studied.(ABSTRACT TRUNCATED AT 250 WORDS)