Combined angiotensin II receptor antagonism and angiotensin-converting enzyme inhibition further attenuates postinfarction left ventricular remodeling.

BACKGROUND: ACE inhibition (ACEI) attenuates post-myocardial infarction (MI) LV remodeling, but the effects of angiotensin II type 1 receptor (AT(1)) antagonism alone or in combination with ACEI are unclear. Accordingly, we investigated the effects of AT(1) antagonism, ACEI, and their combination in a well-characterized ovine postinfarction model. METHODS AND RESULTS: Beginning 2 days after transmural anteroapical MI, 62 sheep were treated with 1 of 5 treatment regimens: no therapy (control, n=12), standard-dose ACEI (sACEI; ramipril 10 mg/d, n=14), high-dose ACEI (hACEI; ramipril 20 mg/d, n=8), AT(1) blockade (losartan 50 mg/d, n=13), and combination therapy with sACEI+AT(1) blockade (CT; ramipril 10 mg/d+losartan 50 mg/d, n=15). MRI was performed before and 8 weeks after MI to quantify changes in LV end-diastolic and end-systolic volume indices (DeltaEDVI, DeltaESVI) and ejection fraction (DeltaEF). Change in regional percent intramyocardial circumferential shortening in noninfarcted segments adjacent to the infarct (Adj Delta%S) was measured by tagged MRI. CT resulted in the most marked blunting of LV remodeling: DeltaESVI (+1.0+/-0.4, +0.7+/-0.4, +0.6+/-0.3, +0.9+/-0.5, and +0.4+/-0.2* mL/kg); DeltaEDVI (+0.9+/-0.4, +0.7+/-0.5, +0.6+/-0.5, +0.9+/-0.5, and +0.4+/-0.3 mL/kg); DeltaEF (-24+/-7, -18+/-6, -14+/-7, -18+/-10, and -11+/-9* %); and Adj Delta%S (-8+/-4, -7+/-3, -5+/-3, -5+/-3, and -2+/-3* %) for Control, sACEI, hACEI, AT(1) blockade, and CT, respectively (*P<0.04 versus sACEI, AT(1) blockade, and control; P<0.05 versus control; P<0.002 versus AT(1) blockade and control). EDVI and ESVI at 8 weeks after MI were smallest with CT (P<0.02 versus all). CONCLUSIONS: Combination therapy with sACEI+AT(1) blockade shows promise in attenuating postinfarction LV remodeling but was not clearly superior to hACEI in the present study.

Echocardiographic visualization of coronary artery anatomy in the adult.

In the light of technologic advances and the development of new imaging planes, the feasibility of two-dimensional echocardiographic visualization of coronary artery anatomy was reevaluated in the adult. Thirty-five subjects were studied using an ultrasonograph equipped with a 3.5 and 5.0 MHz annular array transducer, digital processing and cine loop review. There were 18 normal subjects and 17 patients with heart disease, including 9 patients with valvular, 5 patients with coronary, 2 patients with congenital and 1 patient with cardiomyopathic disease. The mean age was 47 +/- 18 years (range 17 to 79). Modifications of standard parasternal and apical views permitted high quality images of portions of each of the major epicardial vessels adequate for assessment of luminal diameter. The left main coronary artery was seen in 30 (86%) of the 35 subjects and its bifurcation was seen in 15. The left anterior descending coronary artery was seen in 30 subjects (mean length 3.9 +/- 2.3 cm, maximal length 7.5), the left circumflex artery in 11 (1.1 +/- 1.0, maximal 3.0) and the right coronary artery in 32 (5.6 +/- 2.6, maximal 12). Proximal and mid portions of the left anterior descending artery were seen in 23 and 11 subjects, respectively. The average proximal length visualized was 4.2 cm, and the average luminal diameter visualized was 4.9 mm. The average length of the mid left anterior descending coronary artery seen was 1.9 cm and the average luminal diameter seen was 4.6 mm. The proximal right coronary artery was seen in 17 subjects (average visualized length 2.7 cm and average diameter 3.1 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in diastolic function in response to progressive left ventricular hypertrophy.

To examine the time course of the functional consequences of progressive left ventricular hypertrophy, diastolic left ventricular inflow and wall thinning variables were analyzed in 13 dogs before and 2, 4, 8 and 12 weeks after creation of perinephritic hypertension. Left ventricular echocardiograms were digitized for dimensions, mass and peak rates of wall thinning (-dh/dt/h) and cavity enlargement (dD/dt/D). Doppler recordings of left ventricular inflow were analyzed for peak early (E) and late (A) diastolic inflow velocities, their ratio and atrial filling fraction. At 2 weeks, systolic blood pressure increased from 151 to 233 mm Hg, wall stress from 52 to 80 kdynes/cm2 and posterior wall thickness from 0.68 to 0.84 cm (all p less than 0.05). Left ventricular mass increased from 90 to 115 g over 12 weeks (p less than 0.05). Heart rate, cavity size and systolic shortening were unchanged at all data points. Diastolic abnormalities accompanied the developing hypertrophy and included impairment of early function, as demonstrated by a peak rate of wall thinning, from -13.4 to -8.9 l/s at 2 weeks (p less than 0.05), increased dependence on atrial systolic filling, a decrease in E/A from 1.68 to 1.29 at 4 weeks (p less than 0.05) and an increase in atrial filling fraction from 30% to 43% at 8 weeks (p = NS). Thus, diastolic dysfunction is an early consequence of experimental left ventricular hypertrophy. Different aspects of diastolic impairment are sensitively reflected by echocardiographic Doppler recordings, suggesting that these methods should be useful for the detection of diastolic dysfunction in human patients.

An unusual case of postoperative pseudoaneurysm of the left ventricle: Doppler echocardiographic findings.

Two years and 9 months after aneurysmectomy of a true left ventricular aneurysm, a 55 year old man presented with clinical features suggestive of acute pericarditis. The echocardiogram revealed a large echo-free space outside the heart. Doppler study showed phasic flow between the echo-free space and the left ventricular cavity through a distinct interruption of the left ventricular apical wall endocardial echoes. The diagnosis of pseudoaneurysm was made and was subsequently confirmed by angiographic and operative findings. After successful repair, a repeat Doppler echocardiographic examination showed a marked reduction in the echo-free space, absence of communication with the left ventricle and no flow signal in the space.

Different effects of prolonged exercise on the right and left ventricles.

To examine the functional consequences of the greater increase in right ventricular work with exercise, the effects of prolonged exercise on the right and left heart chambers were compared in 41 athletes before, at the finish (13 min) and after recovery (28 h) from the Hawaii Ironman Triathlon (3.9 km swim, 180.2 km bike ride, 42.2 km run). Two-dimensional and Doppler echocardiograms were analyzed for left and right atrial and ventricular areas at end-diastole and end-systole, right and left ventricular inflow velocities and mitral and tricuspid regurgitation. After exercise, left ventricular and left and right atrial sizes were reduced, whereas right ventricular size increased (diastole: 21.4 to 24.2 cm2; systole: 15.8 to 18.2 cm2; p less than 0.01). The emptying fraction of all chambers was unchanged. Left but not right ventricular inflow showed an increase in peak velocity of rapid filling, whereas both atrial systolic velocities increased (26 to 38 cm/s tricuspid; 38 to 54 cm/s mitral; both p less than 0.01). Overall, the right ventricular early to atrial velocity ratio was reduced after exercise (1.56 to 1.17; p less than 0.05) and the left ventricular pattern was unchanged. The prevalence of tricuspid regurgitation was statistically unchanged (86% to 52%), although that of mitral regurgitation was greatly reduced (76% to 0%). Changes in all variables returned toward prerace values during recovery. Thus, in highly trained athletes, prolonged exercise causes differing responses of the right and left ventricles. These differences may be due to changes in right ventricular function, shape or compliance.

Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy.

Because idiopathic dilated cardiomyopathy is characterized by elevated wall stress and a more spherical left ventricle, the relations among shape, afterload and survival were examined. Thirty-six patients with cardiomyopathy were prospectively studied by two-dimensional echocardiography. Data included echocardiographic short- and long-axis cavity dimensions, their ratio and, with cuff systolic blood pressure, meridional and circumferential end-systolic stress and their ratios. Survivors (n = 16) were followed up for 52 months (range 40 to 76); nonsurvivors (n = 20) died an average of 11 months after study. Survivors had a smaller left ventricular end-diastolic short-axis dimension (6.4 versus 7.1 cm, p less than 0.03) but a similar long-axis length (8.6 versus 8.3 cm). However, overall cavity shape or the ratio of short- to long-axis end-diastolic dimensions was more spherical in those with poorer survival (ratio 0.76 versus 0.68, p less than 0.02). Meridional and circumferential end-systolic stresses were similar in the two groups, but stress was more evenly distributed in the long- and short-axis planes in nonsurvivors (meridional/circumferential stress ratio 0.57 versus 0.52 in survivors, p less than 0.05). Improved survival was associated with an end-diastolic short-axis dimension less than 7.63 cm, a short- to long-axis ratio less than 0.76 and a meridional to circumferential stress ratio less than 0.54. Life table analysis revealed a 28% mortality rate in patients with all three of these characteristics compared with 100% in patients with none. Survivors and nonsurvivors did not differ in systolic cavity dimension, wall thickness, relative wall thickness, cavity volume, percent posterior wall thickening or fractional shortening.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of echocardiographic 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.

Dynamic three-dimensional reconstruction of the left ventricle from two-dimensional echocardiograms.

Using an open chest canine model, a method was developed for three-dimensional reconstruction of the contracting left ventricle from two-dimensional echocardiograms, which is applicable to intraoperative studies in humans. A mechanically held 5 MHz transducer was used to record parallel high resolution cross-sectional images with precise spatial registration. Myocardial borders were tracked manually and entered into a computer system. Regional filling and interpolation routines were applied to reconstruct the endocardial and epicardial surfaces of the ventricle. The myocardium can be displayed as a translucent, shaded three-dimensional solid surrounding the ventricular cavity. One or both surfaces can be rotated about any axis, sectioned through any plane and viewed in motion through systole and diastole. Studies before and after left anterior descending coronary artery occlusion showed the three-dimensional extent of abnormal left ventricular cavity and myocardial deformation. Quantitative examination of regions of interest permits the analysis of global and regional volumetric and myocardial thickness changes throughout the cardiac cycle. Thus, open chest three-dimensional echocardiography provides a powerful tool for the quantitative physiologic investigation of the left ventricle.

Intracoronary Doppler guide wire versus stress single-photon emission computed tomographic thallium-201 imaging in assessment of intermediate coronary stenoses.

OBJECTIVES: The purpose of this study was to compare measures of coronary flow reserve by an intracoronary Doppler guide wire with results of stress single-photon emission computed tomographic (SPECT) thallium-201 imaging in patients with intermediate coronary artery disease (40% to 70% stenosis). BACKGROUND: Visual assessment of the coronary arteriogram as a means of predicting the physiologic significance of intermediate coronary stenoses is inaccurate. Coronary flow reserve is a reliable marker of the functional importance of a coronary lesion. The recent development of an intracoronary Doppler guide wire permits routine assessment of coronary flow reserve distal to coronary artery stenoses. METHODS: We prospectively evaluated coronary flow reserve in 30 subjects with intermediate stenoses using an intracoronary Doppler guide wire during elective coronary angiography. Patients subsequently underwent stress SPECT thallium-201 testing, and the blinded interpretations were correlated. Coronary flow reserve in a control group with normal coronary arteries classified our sample into group 1 (abnormal flow reserve, < 2.0) and group 2 (normal flow reserve, > or = 2.0). RESULTS: As defined, the coronary flow reserve of 16 vessels in group 1 was diminished in comparison to that of 19 vessels in group 2 (p = 0.0001). Qualitative and quantitative analysis of stress SPECT thallium-201 images confirmed perfusion defects in 15 of 16 vascular territories in group 1 in contrast to 1 of 19 regions in group 2. The sensitivity, specificity and overall predictive accuracy of Doppler-determined coronary flow reserve for stress SPECT thallium-201 results were 94%, 95% and 94%, respectively. CONCLUSIONS: In appropriately selected patients with intermediate coronary artery stenoses, Doppler guide wire determination of lesion significance provides equivalent data to those acquired by stress SPECT thallium-201 imaging.

Dissociation between changes in intramyocardial function and left ventricular volumes in the eight weeks after first anterior myocardial infarction.

OBJECTIVES: We sought to examine the relation between regional changes in intramyocardial function and global left ventricular (LV) remodeling in the first 8 weeks after reperfused first anterior myocardial infarction (MI). BACKGROUND: Because of limitations in imaging methods used to date, this relation has not been thoroughly evaluated. METHODS: We studied 26 patients (21 men, 5 women; mean age 51 years) by magnetic resonance imaging (MRI) on day 5 +/- 2 (mean +/- SD) and week 8 +/- 1 after their first anterior MI. All patients had single-vessel left anterior descending coronary artery disease and although they had received reperfusion therapy, all had regional LV dysfunction and an initial ejection fraction (EF) < or = 50%. Short-axis magnetic resonance tagging was performed spanning the LV. Percent intramyocardial circumferential shortening (%S) on a topographic basis, LV mass index, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index and LV ejection fraction (LVEF) were measured. RESULTS: Left ventricular mass index tended to decrease, whereas the LVEDVI increased from 82 +/- 24 to 96 +/- 27 ml/m2 (p = 0.002). Left ventricular end-systolic volume index remained unchanged, whereas LVEF increased from 39 +/- 12% to 45 +/- 14% (p = 0.002). Apical %S improved from 9 +/- 6% to 13 +/- 5% (p < 0.0001), as it did in the midanterior (6 +/- 6% to 10 +/- 7%, p < 0.02) and midseptal regions (8 +/- 7% to 12 +/- 6%, p < 0.02). Early dysfunction in remote midinferior and basal lateral regions resolved by 8 weeks. By multivariate analysis, the only significant predictor of an increase in LVEDVI over the study period was peak creatine kinase (p = 0.04). CONCLUSIONS: In the first 8 weeks after a large, reperfused anterior MI, %S improved in the apex, midanterior and midseptal regions and normalized in remote noninfarct-related regions, but LV end-diastolic volumes also increased. This increased LVEDVI correlated with infarct size by peak creatine kinase and was not related to changes in global and regional LV function.

Matching of myocardial oxygen consumption to mechanical load in human left ventricular hypertrophy and dysfunction.

The coupling of myocardial oxygen consumption (MVO2) with its determinants in left ventricular hypertrophy in human beings is poorly understood. Therefore, thermodilution-derived coronary blood flow, MVO2 and left ventricular wall stress, obtained from simultaneous left ventricular M-mode echogram and pressure, were compared in 32 patients with various degrees of left ventricular hypertrophy. Patients were studied at rest and after mechanical load alteration with nitroglycerin or phenylephrine. Decreases in MVO2 (-5.7 +/- 0.8 ml/min; p less than 0.001) and the time integral of meridional ejection stress or shortening load (-1,297 +/- 152 X 10(3) dynes X s/cm2; p less than 0.001) were observed after nitroglycerin administration while increases in MVO2 (+5.5 +/- 0.7 ml/min; p less than 0.001) and shortening load (+1,412 +/- 137 X 10(3) dynes X s/cm2; p less than 0.001) were noted after phenylephrine. An index relating the change in MVO2 to the corresponding change in shortening load (SL), % delta MVO2/% delta SL, was significantly different in patients without (Group 1) and with (Group 2) clinical left ventricular failure. Left ventricular mass was similar in both groups. The mean % delta MVO2/% delta SL with phenylephrine in Group 1 (79.6 +/- 9.6) was greater than the index for Group 2 (35.5 +/- 6.1; p less than 0.005). With nitroglycerin, Group 2 patients exhibited a greater reduction in % delta MVO2/% delta SL (110.5 +/- 17.8) than Group 1 (54.0 +/- 9.4; p less than 0.01). In conclusion, in patients with left ventricular hypertrophy and dysfunction there appears to be a state of diminished coronary flow response to load augmentation. However, load reduction in patients with clinical left ventricular failure results in a more balanced relation between oxygen uptake and ejection stress.

Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling.

OBJECTIVES: We examined the association of sympathetic denervation and reduced blood flow with mechanical dysfunction in adjacent noninfarcted regions late after myocardial infarction (MI). BACKGROUND: Using a well characterized ovine model of left ventricular (LV) remodeling after transmural anteroapical MI, we previously showed that histologically normal adjacent noninfarcted regions demonstrate mechanical dysfunction. METHODS: Ten sheep underwent coronary ligation. Magnetic resonance imaging was performed before and 8 weeks after infarction for measurement of LV mass, volumes, ejection fraction and regional intramyocardial circumferential shortening (%S). Iodine-123 metaiodobenzylguanidine (I-123 MIBG) and fluorescent microspheres before and after administration of adenosine were infused before death for measurement of sympathetic innervation, blood flow and blood flow reserve from matched postmortem regions. RESULTS: From baseline to 8 weeks after infarction, LV end-diastolic volume increased from (mean +/- SD) 1.5 +/- 0.3 to 2.6 +/- 0.5 ml/kg (p < 0.001), and LV mass increased from 2.0 +/- 0.3 to 2.6 +/- 0.5 g/kg (p = 0.001). Regionally, the decline in subendocardial %S was greater in adjacent (19 +/- 5% to 8 +/- 5%) than in remote noninfarcted regions (20 +/- 6% to 19 +/- 6%, p < 0.002). No difference in regional blood flow or blood flow reserve was found between adjacent and remote regions, whereas I-123 MIBG uptake was lower in adjacent than in remote myocardium (1.09 +/- 0.30 vs. 1.31 +/- 0.40 nmol/g, p < 0.003). Topographically, from apex to base at 8 weeks after infarction, %S correlated closely with I-123 MIBG uptake (r = 0.93, p = 0.003). CONCLUSIONS: In mechanically dysfunctional noninfarcted regions adjacent to chronic transmural myocardial infarction in the remodeled left ventricle, blood flow and blood flow reserve are preserved, yet sympathetic innervation is reduced. Chronic sympathetic denervation in adjacent noninfarcted regions, in association with regional mechanical dysfunction, may contribute to LV remodeling after infarction.

The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report.

OBJECTIVES: The Women's Ischemia Syndrome Evaluation (WISE) is a National Heart, Lung and Blood Institute-sponsored, four-center study designed to: 1) optimize symptom evaluation and diagnostic testing for ischemic heart disease; 2) explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenoses, and 3) evaluate the influence of reproductive hormones on symptoms and diagnostic test response. BACKGROUND: Accurate diagnosis of ischemic heart disease in women is a major challenge to physicians, and the role reproductive hormones play in this diagnostic uncertainty is unexplored. Moreover, the significance and pathophysiology of ischemia in the absence of significant epicardial coronary stenoses is unknown. METHODS: The WISE common core data include demographic and clinical data, symptom and psychosocial variables, coronary angiographic and ventriculographic data, brachial artery reactivity testing, resting/ambulatory electrocardiographic monitoring and a variety of blood determinations. Site-specific complementary methods include physiologic and functional cardiovascular assessments of myocardial perfusion and metabolism, ventriculography, endothelial vascular function and coronary angiography. Women are followed for at least 1 year to assess clinical events and symptom status. RESULTS: In Phase I (1996-1997), a pilot phase, 256 women were studied. These data indicate that the WISE protocol is safe and feasible for identifying symptomatic women with and without significant epicardial coronary artery stenoses. CONCLUSIONS: The WISE study will define contemporary diagnostic testing to evaluate women with suspected ischemic heart disease. Phase II (1997-1999) is ongoing and will study an additional 680 women, for a total WISE enrollment of 936 women. Phase III (2000) will include patient follow-up, data analysis and a National Institutes of Health WISE workshop.

Transient ischemia does not limit subsequent ischemic regional dysfunction in humans: a transesophageal echocardiographic study during minimally invasive coronary artery bypass surgery.

OBJECTIVES: This study sought to assess the effects of sequential coronary artery occlusion during minimally invasive coronary artery bypass graft surgery (CABG) on hemodynamic variables and left ventricular systolic function by means of transesophageal echocardiography (TEE). BACKGROUND: Clinical and experimental studies suggest a protective effect of ischemic preconditioning in patients with acute coronary syndromes. However, the effect of repetitive myocardial ischemia on myocardial mechanical function in humans is not completely understood. METHODS: Seventeen patients with left anterior descending coronary artery (LAD) stenosis > or =70% and normal rest left ventricular systolic function referred for minimally invasive CABG underwent intraoperative TEE for assessment of regional left ventricular wall motion and measurement of hemodynamic variables at baseline (baseline 1), during a 5-min coronary occlusion (occlusion 1), after a 5-min reperfusion period (baseline 2) and a during a second coronary occlusion during bypass anastomosis (occlusion 2). RESULTS: Left ventricular wall motion score (LVWMS) increased significantly from baseline (16.0) to occlusion 1 (21.4+/-3.1 [mean +/- SD], p < 0.05) and occlusion 2 (21.8+/-3.1, p < 0.05). No difference in LVWMS was noted between occlusions 1 and 2. Pulmonary artery systolic pressure increased significantly from baseline (25+/-6 mm Hg) to occlusion 1 (32+/-7 mm Hg, p < 0.05) and occlusion 2 (33+/-6 mm Hg, p < 0.05). Pulmonary artery diastolic pressure also increased significantly from baseline (12+/-4 mm Hg) to occlusion 1 (16+/-4 mm Hg, p < 0.05) and occlusion 2 (16+/-4 mm Hg, p < 0.05). No significant differences in pulmonary artery pressures were noted between occlusions 1 and 2. CONCLUSIONS: Ischemic dysfunction was precipitated by the 5-min LAD occlusion, as shown by the increase in LVWMS and pulmonary artery pressure. However, a 5-min coronary occlusion and the resulting ischemia do not alter regional left ventricular systolic function during subsequent ischemia in humans.

Angiotensin-converting enzyme inhibition limits dysfunction in adjacent noninfarcted regions during left ventricular remodeling.

OBJECTIVES: We hypothesized that angiotensin-converting enzyme inhibitors would limit dysfunction in the first 8 weeks after transmural infarction in adjacent noninfarcted regions, as well as attenuate left ventricular remodeling. BACKGROUND: Angiotensin-converting enzyme inhibition limits ventricular dilation and hypertrophy and improves survival after anterior infarction, but its effect on regional function during remodeling is not well characterized. METHODS: Thirteen sheep underwent coronary ligation to create an anteroapical infarction. At postinfarction day 2, eight sheep were randomized to therapy with the angiotensin-converting enzyme inhibitor ramipril, and five sheep received no therapy. Animals were studied with magnetic resonance myocardial tagging before and 8 weeks after infarction. Left ventricular volume, mass and ejection fraction were measured, as were changes in percent circumferential shortening within the subendocardium and subepicardium of infarcted and noninfarcted myocardium, both adjacent to and remote from the infarction. RESULTS: Angiotensin-converting enzyme inhibition limited the increase in end-diastolic volume from a mean (+/- SD) of +1.5 +/- 0.7 ml/kg in control animals to +0.5 +/- 0.8 ml/kg in the treated group (p < 0.04). Segmental function within infarcted and remote noninfarcted tissue did not differ between groups. However, angiotensin-converting enzyme inhibition limited the decline in function in the adjacent noninfarcted region 8 weeks after infarction. Percent circumferential shortening in the subendocardium decreased by -13 +/- 5% in the control group compared with -5 +/- 5% in the treated group (p < 0.03). CONCLUSIONS: In concert with a reduction in left ventricular remodeling after anterior infarction, angiotensin-converting enzyme inhibition limits the decline in function in the adjacent noninfarcted region. Dysfunction in adjacent noninfarcted regions may be an important determinant of left ventricular remodeling after infarction.

Weight cycling and high-density lipoprotein cholesterol in women: evidence of an adverse effect: a report from the NHLBI-sponsored WISE study. Women's Ischemia Syndrome Evaluation Study Group.

OBJECTIVES: We undertook an analysis of weight cycling, coronary risk factors and angiographic coronary artery disease (CAD) in women. BACKGROUND: The effect of weight cycling on cardiovascular mortality and morbidity is controversial, and the impact of weight cycling on cardiovascular risk factors is unclear. METHODS: This is a cross-sectional population study of 485 women with coronary risk factors undergoing coronary angiography for evaluation of suspected myocardial ischemia enrolled in the Women's Ischemia Syndrome Evaluation (WISE). Reported lifetime weight cycling-defined as voluntary weight loss of at least 10 lbs at least 3 times--coronary risk factors including core laboratory determined blood lipoproteins and CAD, as determined by a core angiographic laboratory, are the main outcome measures. RESULTS: Overall, 27% of women reported weight cycling--19% cycled 10 to 19 lbs, 6% cycled 20 to 49 lbs, and 2% cycled 50+ lbs. Reported weight cycling was associated with 7% lower high-density lipoprotein cholesterol (HDL-C) levels in women (p = 0.01). The HDL-C effect was directly related to the amount of weight cycled with women who lost > or = 50 lbs/cycle having HDL-C levels 27% lower than noncyclers (p = 0.0025). This finding was independent of other HDL-C modulators, including estrogen status, physical activity level, alcohol intake, body mass index, diabetes, beta-blocker use, cigarette smoking and race. Weight cycling was not associated with an increased prevalence of CAD in this population. CONCLUSIONS: Weight cycling is associated with lower HDL-C in women of a magnitude that is known to be associated with an increased risk of cardiac events as demonstrated in prior clinical trials.

Validation of in vivo myocardial strain measurement by magnetic resonance tagging with sonomicrometry.

OBJECTIVES: This study was designed to validate strain measurements obtained using magnetic resonance tagging with spatial modulation of magnetization (SPAMM). We compared circumferential segment shortening measurements (%S) obtained using SPAMM to sonomicrometry %S in a canine model with (n = 28) and without (n = 3) coronary artery ligation. BACKGROUND: Magnetic resonance tagging enables noninvasive measurement of myocardial strain, but such strain measurements have not yet been validated in vivo. METHODS: Circumferential sonomicrometry crystal pairs were placed in apical myocardium at ischemic risk in ligation studies and in adjacent and remote myocardium. The %S was obtained from closely juxtaposed sonomicrometry and SPAMM sites. RESULTS: Paired data were available from 19 of 31 studies. Both methods distinguished remote from ischemic function effectively (p = 0.014 for SPAMM and p = 0.002 for sonomicrometry). SPAMM %S was similar to sonomicrometry %S in ischemic myocardium (2 +/- 3 vs. 0 +/- 3 p = 0.067) but was slightly higher than sonomicrometry %S in remote myocardium (11 +/- 10 vs. 7 +/- 5, p = 0.033). End-systolic (n = 30) and late systolic (n = 34) SPAMM %S correlated well with sonomicrometry %S (r = 0.84, p < 0.0001 and r = 0.88, p < 0.0001). CONCLUSIONS: Magnetic resonance tagging using SPAMM can quantitate myocardial strain in ischemic and remote myocardium. This study validates its application in scientific investigation and clinical assessment of patients with myocardial ischemia.

Age-associated changes in regional aortic pulse wave velocity.

OBJECTIVES: This study was designed to determine noninvasively the age-associated changes in regional mechanical properties in normals using phase-contrast magnetic resonance imaging (PCMRI). BACKGROUND: It has been well documented that there is a progressive increase in aortic pulse wave velocity (PWV) with age. Previously, PWV has been measured at a single aortic location, or has compared arterial waves between carotid and femoral points to determine PWV. METHODS: Applanation tonometry (TONO) and in-plane PCMR was performed in 24 volunteers (12 men) ranging in age from 21 to 72 years old. The PCMRI PWV was measured in three aortic segments. As validation, TONO was performed to determine PWV between the carotid and femoral artery. RESULTS: When PCMRI PWV was averaged over the three locations, it was not different from TONO (7.9 +/- 2.3 vs. 7.6 +/- 2.4 m/s, respectively). When the volunteers were divided into groups of < 55 and > or =55 years old, the younger group showed similar PWV at each aortic location. However, the older group displayed significantly increased PWV in the region spanning the ascending and proximal descending aorta compared with the mid-thoracic or abdominal segments (10.6 +/- 2.5 m/s, 9.2 +/- 2.8 m/s, and 7.1 +/- 1.7 m/s, respectively, p < 0.001, analysis of variance). CONCLUSIONS: In-plane PCMRI permits determination of PWV in multiple aortic locations in a single acquisition. Progressive fragmentation of elastic fibers and alterations in the regulation of vascular tone may result in an age-related, regional increase in PWV primarily affecting the proximal aorta.

Dobutamine stress echocardiography in women with chest pain. Pilot phase data from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE).

OBJECTIVES: The aim of this project was to assess the utility of dobutamine stress echocardiography (DSE) for evaluation of women with suspected ischemic heart disease. BACKGROUND: Most investigations addressing efficacy of diagnosis and treatment of coronary artery disease (CAD) have been performed in predominantly male populations. As part of the Women's Ischemia Syndrome Evaluation (WISE) study, DSE was assessed in women participating at the University of Florida clinical site. METHODS: Women with chest pain or other symptoms suggestive of myocardial ischemia and clinically indicated coronary angiography were eligible for the WISE study. Enrolled subjects underwent DSE using a modified protocol. Coronary stenosis was assessed by core laboratory quantitative coronary angiography (QCA). RESULTS: The 92 women studied ranged in age from 34 to 82 years (mean 57.5). All women had > or = 1 major risk for CAD, and most (89, 97%) had > or = 2 risk factors. In 78 women (85%), left ventricular wall motion was normal at baseline and during peak infusion. The remaining 14 women had wall motion abnormalities during DSE. By QCA, 25 women (27%) had > or = 50% coronary stenosis, including 10 with single-vessel obstruction. Dobutamine stress echocardiography was abnormal in 10 of these 25 women, yielding overall sensitivity of 40%, and 60% for multivessel stenosis. Exclusion of women with inadequate heart rate response yielded overall sensitivity of 50%, and 81.8% for multivessel stenosis. Dobutamine stress echocardiography was normal in 54 of the 67 women with < 50% coronary narrowing, specificity 80.6%. CONCLUSIONS: Dobutamine stress echocardiography reliably detects multivessel stenosis in women with suspected CAD. However, DSE is usually negative in women with single-vessel stenosis, and in the larger subset without coronary stenosis. Ongoing protocols of the WISE study are expected to improve diagnostic accuracy in women with single-vessel disease, as well as provide important data in the substantial number of women with chest pain but without epicardial coronary artery stenosis.

Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease. Results from the pilot phase of the Women's Ischemia Syndrome Evaluation (WISE) study.

OBJECTIVES: We sought to develop and validate a definition of coronary microvascular dysfunction in women with chest pain and no significant epicardial obstruction based on adenosine-induced changes in coronary flow velocity (i.e., coronary velocity reserve). BACKGROUND: Chest pain is frequently not caused by fixed obstructive coronary artery disease (CAD) of large vessels in women. Coronary microvascular dysfunction is an alternative mechanism of chest pain that is more prevalent in women and is associated with attenuated coronary volumetric flow augmentation in response to hyperemic stimuli (i.e., abnormal coronary flow reserve). However, traditional assessment of coronary volumetric flow reserve is time-consuming and not uniformly available. METHODS: As part of the Women's Ischemia Syndrome Evaluation (WISE) study, 48 women with chest pain and normal coronary arteries or minimal coronary luminal irregularities (mean stenosis = 7%) underwent assessment of coronary blood flow reserve and coronary flow velocity reserve. Blood flow responses to intracoronary adenosine were measured using intracoronary Doppler ultrasonography and quantitative angiography. RESULTS: Coronary volumetric flow reserve correlated with coronary velocity reserve (Pearson correlation = 0.87, p < 0.001). In 29 (60%) women with abnormal coronary microcirculation (mean coronary flow reserve = 1.84), adenosine increased coronary velocity by 89% (p < 0.001) but did not change coronary cross-sectional area. In 19 (40%) women with normal microcirculation (mean flow reserve = 3.24), adenosine increased coronary velocity and area by 179% (p < 0.001) and 17% (p < 0.001), respectively. A coronary velocity reserve threshold of 2.24 provided the best balance between sensitivity and specificity (90% and 89%, respectively) for the diagnosis of microvascular dysfunction. In addition, failure of the epicardial coronary to dilate at least 9% was found to be a sensitive (79%) and specific (79%) surrogate marker of microvascular dysfunction. CONCLUSIONS: Coronary flow velocity response to intracoronary adenosine characterizes coronary microvascular function in women with chest pain in the absence of obstructive CAD. Attenuated epicardial coronary dilation response to adenosine may be a surrogate marker of microvascular dysfunction in women with chest pain and no obstructive CAD.