Endothelial function in women of the Kronos Early Estrogen Prevention Study.

OBJECTIVE: Endothelial dysfunction occurs early in the atherosclerotic disease process, often preceding clinical symptoms. Use of menopausal hormone treatment (MHT) to reduce cardiovascular risk is controversial. This study evaluated effects of 4 years of MHT on endothelial function in healthy, recently menopausal women. METHODS: Endothelial function was determined by pulse volume digital tonometry providing a reactive hyperemia index (RHI) in a subset of women enrolled in the Kronos Early Estrogen Prevention Study. RHI was measured before and annually after randomization to daily oral conjugated equine estrogen (oCEE, 0.45 mg), weekly transdermal 17ß-estradiol (tE2, 50 µg) each with intermittent progesterone (200 mg daily 12 days of the month) or placebo pills and patch. RESULTS: At baseline, RHI averaged 2.39 ± 0.69 (mean ± standard deviation; n = 83), and over follow-up did not differ significantly among groups: oCEE, 2.26 ± 0.48 (n = 26); tE2, 2.26 ± 0.45 (n = 24); and placebo, 2.37 ± 0.37 (n = 33). Changes in RHI did not correlate with changes in traditional cardiovascular risk factors, but may inversely correlate with carotid intima medial thickness (Spearman correlation coefficient ρ = -0.268, p = 0.012). CONCLUSION: In this 4-year prospective assessment of recently menopausal women, MHT did not significantly alter RHI when compared to placebo.

Endothelial function and cardiovascular risk stratification in menopausal women.

BACKGROUND: Peripheral arterial, endothelium-dependent, flow-mediated reactive hyperemia is reduced in individuals with atherosclerosis. This study tested the hypothesis that digital tonometry, as a surrogate of endothelial function, is useful to stratify cardiovascular risk in recently menopausal women who are asymptomatic for cardiovascular disease. METHODS: Women undergoing screening for the Kronos Early Estrogen Prevention Study (KEEPS) were evaluated for conventional risk factors, flow-mediated reactive hyperemia by digital tonometry (RHI), carotid intima-media thickness (CIMT) by ultrasound, and coronary arterial calcium (CAC) by 64-slice CT scanner. RESULTS: One hundred and two non-diabetic Caucasian women (53.0 +/- 2.3 years old, 18.0 +/- 9.0 months past their last menses) participated; 72% were never-smokers. Fourteen women had positive CAC scores (range 0.5-133 Agatston units); CIMT ranged from 0.57 to 1.06 mm. RHI ranged from 1.26 to 5.44. RHI did not correlate with time past menopause, CAC, CIMT, total cholesterol or low density lipoprotein cholesterol. The significant negative correlation of RHI with body mass index (r = -0.21, p = 0.031) was lost in non-smokers (r = - 0.17, p = 0.14). There was also a negative correlation of high density lipoprotein cholesterol with CAC, both in the overall group and non-smokers (rho = -0.20, p = 0.05 and rho = -0.27, p = 0.02, respectively). CONCLUSIONS: RHI varies widely in healthy women within the first 3 years of menopause. RHI was not associated with standard risk assessment algorithms, CAC or CIMT. RHI may indicate an additional, independent component and non-invasive tool to further stratify cardiovascular risk in recently menopausal women. As KEEPS continues, data on RHI will provide information regarding hormonal therapy, endovascular biology and atherosclerotic risk.

Second harmonic imaging of an intravenously administered echocardiographic contrast agent: Visualization of coronary arteries and measurement of coronary blood flow.

OBJECTIVES: This study sought to evaluate the potential of second harmonic contrast echocardiography to assess coronary vasculature. BACKGROUND: Newer transpulmonary ultrasound contrast agents capable of resonance phenomena detected by harmonic imaging may theoretically be able to demonstrate blood flow in the myocardium. METHODS: Transthoracic B-mode images and Doppler were obtained using a prototype second harmonic ultrasound system after femoral vein injection of AF0145 (10 to 40 mg) in 13 closed chest dogs (mean weight 25.6 kg). Coronary Doppler flow was simultaneously invasively measured using an intracoronary flow wire and visually compared with transthoracic Doppler flow. "Noninvasive" coronary vasodilator reserve was determined by measuring the ratio of the Doppler time velocity integral after adenosine to the baseline value and compared with the "invasive" intracoronary determination. RESULTS: Harmonic imaging showed heterogeneous opacification of the myocardium characterized by linear branching structures consistent with intramyocardial coronary arteries, which were not clearly visible during conventional ultrasound imaging. In nine dogs, transthoracic Doppler was performed, and characteristic coronary Doppler flow was observed, identical to the simultaneously observed intracoronary Doppler flow. Intracoronary adenosine (120 to 150 microgram) equally increased intracoronary and transthoracic Doppler flow velocities. The calculated "noninvasive" and "invasive" coronary vasodilator reserve ratios were similar ([mean +/- SD] 3.3 +/- 1.0 and 3.6 +/- 1.2, p = NS), with excellent correlation (r = 0.95, p = 0.0012). CONCLUSIONS: These findings indicate that noninvasive assessment of intramyocardial coronary vasculature and measurement of coronary blood flow reserve are possible using second harmonic contrast echocardiography.

Usefulness of nuclear magnetic resonance imaging for evaluation of pericardial effusions, and comparison with two-dimensional echocardiography.

Nuclear magnetic resonance (NMR) imaging clearly delineates cardiovascular structures without interference from overlying bone and lung tissue. The techniques of NMR imaging and echocardiography were compared in 26 patients with pericardial effusions, 10 of whom had associated pleural effusions. In those patients with fluid detected by both techniques, estimated size of the effusion tended to be somewhat larger by NMR. NMR imaging detected several small pericardial effusions that were not visualized by echocardiography. Both techniques demonstrated loculation well, although NMR imaging was better for detecting fluid located superiorly at the aortic pericardial reflection site, medially at the border of the right atrium and posteriorly at the left ventricular apex. In the 14 patients with documented exudative effusions (10 pericardial, 4 pleural) NMR signals of varying intensity were present in the effusion. One patient had a documented transudative effusion and no NMR signal was observed in the fluid. NMR imaging clearly distinguished pericardial from pleural effusions. NMR imaging is indicated when a suspected pericardial effusions is not detected by echocardiography or when specific localization or fluid characterization is desired.

Characterization of acute myocardial infarction by magnetic resonance imaging.

The T2-weighted spin-echo technique is currently the most frequently used magnetic resonance imaging (MRI) method to visualize acute myocardial infarction. However, image quality is often degraded by ghost artifacts from blood flow, and respiratory and cardiac contractile motion. To enhance the usefulness of this technique for detailed characterization of infarction, a velocity-compensated spin-echo pulse sequence was tested by imaging a flow phantom, 6 normal subjects and 17 patients with acute myocardial infarction. After preliminary studies were performed in 7 patients to determine optimal imaging parameters, a standardized imaging protocol was used in the next 10. The location of myocardial infarction identified by the electrocardiogram and coronary anatomy was correctly identified in 10 of 10 patients. Distribution of the injury within the left ventricle was clearly visualized, and showed that patients often had a mixture of transmural and nontransmural injury. Heterogenous distribution of signal intensity within the infarction suggested the presence of hemorrhage. Papillary muscle involvement was readily apparent. Signal intensity of the infarction (brightest segment) was increased by 89 +/- 31% compared with the mean of the remote segments. The myocardial/skeletal muscle ratio was significantly (p less than 0.001) increased for the infarction segments compared with that for remote myocardium, allowing quantitative analysis of segmental signal intensity. The MRI wall motion study obtained as part of this protocol demonstrated wall thickening in 58% of the infarction segments and in 6 of 10 patients. This finding suggested the presence of reversibly injured myocardium. In conclusion, the results demonstrate the potential of MRI for detailed tissue characterization after acute myocardial infarction.

Usefulness of harmonic imaging for left ventricular opacification and endocardial border delineation by optison.

Harmonic and fundamental imaging techniques were directly compared in 20 patients undergoing intravenous contrast echocardiography for enhancement of left ventricular endocardial border definition. Harmonic imaging demonstrated significantly enhanced left ventricular endocardial border detection and improved the duration and intensity of a contrast effect despite a reduced dosing requirement.

Nuclear magnetic resonance imaging of acute myocardial infarction within 24 hours of chest pain onset.

The present study was intended to establish the feasibility, safety and usefulness of conventional spin-echo nuclear magnetic resonance (NMR) imaging for the detection of acute myocardial infarction within 24 hours of the onset of chest pain. Monitoring facilities were established in the NMR imaging suite that provided the same level of reliability and safety found in a standard coronary care unit. An imaging protocol was developed that allowed the acquisition of a complete study in 30 minutes while providing useful information about mechanical function and myocardial tissue contrast. Eighteen postthrombolysis patients were imaged within 21 +/- 2 hours of chest pain onset. No patient developed recurrent chest pain or arrhythmias in the NMR imaging suite. Relatively T2-weighted spin-echo images (echo time = 60 ms; repetition time = heart rate) provided interpretable images in 16 patients. Fourteen normal subjects were imaged for comparison. Thirteen of 16 patients had an increase in signal intensity in the region of the infarction. Regional wall thickening was assessed using a floating endocardial centroid technique. Wall motion abnormalities detected by NMR corresponded to those noted by 2-dimensional echocardiography and contrast angiography. Sensitivity, specificity and accuracy for the detection of infarction were 93, 80 and 87%, respectively, when signal intensity and wall thickening abnormalities were combined. In summary, NMR imaging is feasible in patients with acute myocardial infarction within 24 hours of chest pain onset. The study can be conducted safely and it provides useful information about acute myocardial infarction.

Image enhancement by noncontrast harmonic echocardiography. Part I. Qualitative assessment of endocardial visualization.

OBJECTIVE: To determine whether harmonic imaging--use of signals with frequencies twice that of the transmitted ultrasound to produce ultrasound images--can improve endocardial border definition in patients who have technically difficult echocardiograms. METHODS: We studied 29 patients with technically difficult echocardiograms (nonvisualization of 2 or more endocardial segments in a 16-segment model). Apical long-axis, four-chamber, and two-chamber images were acquired during fundamental imaging (at 2.0 and 3.5 MHz) and second harmonic imaging (3.5-MHz receive mode) in random order. Images were digitally stored and subsequently reviewed blindly for endocardial segment score (0 = not visualized; 1 = adequate; or 2 = excellent) and overall ranking of image quality (1 [best] to 3 [worst]). RESULTS: Mean endocardial segment score was significantly better (P < 0.0001) for harmonic imaging (1.02 +/- 0.36) than for either fundamental mode (0.49 +/- 0.21 and 0.57 +/- 0.27 for the 2.0- and 3.5-MHz images, respectively). The harmonic images were ranked as better (P < 0.0001) than those of either fundamental mode: harmonic mean rank was 1.07 in comparison with 2.67 and 2.26 for the 2.0- and 3.5-MHz fundamental images, respectively. CONCLUSION: Noncontrast harmonic imaging appreciably enhances endocardial definition in patients with technically difficult echocardiographic studies and significantly improves overall image quality.

Transient constrictive pericarditis: diagnosis by two-dimensional Doppler echocardiography.

Patients with constrictive pericarditis usually require pericardiectomy to relieve their symptoms. In some patients, however, constrictive pericarditis may resolve spontaneously or with medical treatment. Four patients with transient constrictive pericarditis are described in this report. Although the cause of pericarditis differed, all patients had a small to large amount of pericardial effusion, followed by symptoms, signs, and Doppler features typical of constrictive pericarditis. Symptomatic improvement occurred after treatment with some combination of nonsteroidal anti-inflammatory agents, corticosteroids, and antibiotics. The resolution of the symptoms paralleled the normalization of characteristic respiratory changes in Doppler flow velocities. The condition of our patients most likely was related to a transient inflammation (or thickening) of the pericardium due to viral, bacterial, or immunologically mediated pericarditis. Resolution of the thickened pericardium was documented by magnetic resonance imaging in one patient. Awareness of the possible transient nature of constrictive pericarditis in a subgroup of patients with constriction has important clinical implications when pericardiectomy is considered. The resolution of constrictive pericarditis can be documented by serial Doppler echocardiographic examination.

Image enhancement by noncontrast harmonic echocardiography. Part II. Quantitative assessment with use of contrast-to-speckle ratio.

OBJECTIVE: To ascertain whether "harmonic imaging"--use of ultrasound signals with the frequency twice that of the transmitted signal for ultrasound image generation--can improve image contrast while reducing noise. METHODS: Technically difficult echocardiograms (nonvisualization of 2 or more endocardial segments in a 16-segment model) from 25 patients were analyzed. Corresponding fundamental and harmonic images of the left ventricle in the apical four-chamber, two-chamber, and long-axis views were divided into basal, mid, and apical regions. The difference in image quality between fundamental and harmonic scans was assessed by using the muscle-to-cavity contrast-to-speckle ratio (CSRmc). RESULTS: The mean CSRmc values of pooled data revealed significant image enhancement by harmonic scanning (CSRmc increased from 0.84 to 1.06; P < 0.0001). Regression analysis showed that harmonic imaging improved the CSRmc values in 68% of all scans. Regional analysis indicated the most enhancement in basal regions (CSRmc increased from 0.96 to 1.34; P < 0.0001), followed by the mid (CSRmc increased from 0.84 to 1.04; P < 0.0001) and apical (CSRmc increased from 0.68 to 0.74; P = 0.0138) left ventricular regions. CONCLUSION: Noncontrast harmonic imaging significantly enhances suboptimal echocardiographic images, particularly in the regions distant from the transducer.

Leg mass and lower body negative pressure tolerance in men and women.

To explore the hypothesis that lower body muscle mass correlates with orthostatic tolerance, 18 healthy volunteers (age 18-48 yr; 10 men, 8 women) underwent a graded lower body negative pressure (LBNP) protocol consisting of six, 5-min stages of suction up to 60 mmHg in 10-mmHg increments. Forearm blood flow, heart rate, and blood pressure were measured, and forearm vascular resistance was calculated. Leg muscle mass was assessed by dual-energy X-ray absorptiometry. All subjects received standard intravenous hydration for at least 8 h before the study. Six men and four women completed all stages of LBNP. Four men and four women developed presyncopal symptoms, including marked bradycardia and/or hypotension, at LBNP levels of 30 mmHg (n = 2;1 man, 1 woman), 40 mmHg (n = 2;1 man, 1 woman), and 50 mmHg (n = 4;2 men, 2 women). The presyncopal subjects had leg muscle masses ranging from 19.5 to 25.2 kg in men and from 11.7 to 16.6 kg in women. In subjects who completed all stages of LBNP, leg muscle mass ranged from 17.5 to 24.1 kg in men and from 10.4 to 18.0 kg in women. Leg muscle mass did not differ between presyncopal subjects and those who completed the protocol. Furthermore, there were no differences in the hemodynamic responses to LBNP between subjects with low vs. high leg mass. These data suggest that leg muscle mass is not a critical determinant of LBNP tolerance in otherwise healthy men and women.

Reflex responses to regional venous pooling during lower body negative pressure in humans.

Lower body negative pressure is frequently used to simulate orthostasis. Prior data suggest that venous pooling in abdominal or pelvic regions may have major hemodynamic consequences. Therefore, we developed a simple paradigm for assessing regional contributions to venous pooling during lower body negative pressure. Sixteen healthy men and women underwent graded lower body negative pressure protocols to 60 mmHg while wearing medical anti-shock trousers to prevent venous pooling under three randomized conditions: 1) no trouser inflation (control), 2) only the trouser legs inflated, and 3) the trouser legs and abdominopelvic region inflated. Without trouser inflation, heart rate increased 28 +/- 4 beats/min, mean arterial pressure fell -3 +/- 2 mmHg, and forearm vascular resistance increased 51 +/- 9 units at 60 mmHg lower body negative pressure. With inflation of either the trouser legs or the trouser legs and abdominopelvic region, heart rate and mean arterial pressure did not change during lower body negative pressure. By contrast, although the forearm vasoconstrictor response to lower body negative pressure was attenuated by inflation of the trouser legs (delta forearm vascular resistance 33 +/- 10 units, P < 0.05 vs. control), attenuation was greater with the inflation of the trouser legs and abdominopelvic region (delta forearm vascular resistance 16 +/- 5 units, P < 0.05 vs. control and trouser legs-only inflation). Thus the hemodynamic consequences of pooling in the abdominal and pelvic regions during lower body negative pressure appear to be less than in the legs in healthy individuals.

Echocardiograms during six hours of bedrest at head-down and head-up tilt and during space flight.

Left ventricular end-diastolic volume increased after 4 1/2 to 6 hours of space flight, but was significantly decreased after 5 to 6 days of space flight. To determine the role of acute gravitational effects in this phenomenon, responses to a 6-hour bedrest model of 0 gravity (G; 5 degrees head-down tilt) were compared with those of fractional gravity loads of 1/6 G, 1/3 G, and 2/3 G by using head-up tilts of 10 degrees, 20 degrees, and 42 degrees, respectively. On 4 different days, six healthy male subjects were tilted at one of the four angles for 6 hours. Cardiac dimensions and volumes were determined from two-dimensional and M-mode echocardiograms in the left lateral decubitus position at control (0), 2, 4, and 6 hours. Stroke volume decreased with time (P < .05) for all tilt angles when compared with control. Ejection fraction (EF) at -5 degrees was greater than at +20 degrees and +42 degrees (not significant); EF at +10 degrees was greater than at +42 degrees (not significant). For the tilt angles of -5 degrees, +10 degrees, and +20 degrees, mean heart rate decreased during the first 2 hours, and returned to control or was slightly elevated above control (+20 degrees) by 6 hours (not significant). At the +42 degrees angle of tilt, heart rate was increased above control at hours 2, 4, and 6. There were no significant differences in cardiac output at any time point for any tilt angle.(ABSTRACT TRUNCATED AT 250 WORDS)

Destruction of contrast microbubbles during ultrasound imaging at conventional power output.

Inhomogenous opacification of cardiac chambers has been frequently observed after intravenous administration of long-persisting echocardiographic contrast agents. We observed this phenomenon to be most pronounced at high acoustic powers with incomplete opacification of the left ventricular apex and left ventricular outflow tract. Reducing the acoustic energy to which the contrast was exposed by decreasing transmit power or intermittently suspending insonification resulted in homogenous opacification of the entire left ventricular cavity. We systematically examined the effect of varying insonification power on the persistence of three investigational ultrasound contrast agents in both in vitro and in vivo models. We found an inverse relationship between the insonifying power and the persistence of the contrast agents. Contrast intensity decay could be reduced either by decreasing exposure to ultrasound by minimizing the transmit power of the system or by intermittently suspending ultrasound generation (triggering). Minimization of ultrasound contrast exposure to ultrasound energy thus improves echocardiographic contrast duration and homogeneity.

Entrapment of subvalvular mitral tissue causing intermittent failure of a St Jude mitral prosthesis.

Frequently portions of the mitral valve and sub-valvular apparatus are left intact during mitral valve replacement to help preserve left ventricular function. We describe a patient with paroxysmal congestive heart failure caused by intermittent entrapment of the subvalvular apparatus in the prosthesis, preventing complete valve closure.

Contrast dobutamine stress echocardiography: clinical practice assessment in 300 consecutive patients.

In this study we compared non-contrast imaging with contrast imaging of the left ventricle during dobutamine stress echocardiography (DSE). Wall segment visualization, image quality, and confidence of interpretation were determined with and without the use of intravenous Optison, a second-generation echocardiographic contrast agent, in 300 consecutive patients undergoing rest and peak DSE. At rest and at peak stress, the percentage of wall segments visualized, image quality, and confidence of interpretation were better with contrast compared with non-contrast imaging. No significant decrease was seen in wall segment visualization, image quality, or confidence of interpretation from rest to peak stress in images obtained with contrast, unlike the images obtained without contrast from rest to peak stress. The use of the intravenous echocardiographic contrast agent Optison during DSE significantly improved wall segment visualization and image quality at rest and at peak stress, resulting in improved confidence of interpretation.

Contrast echocardiography: current and future applications.

Recent updates in the field of echocardiography have resulted in improvements in image quality, especially in those patients whose ultrasonographic (ultrasound) evaluation was previously suboptimal. Intravenous contrast agents are now available in the United States and Europe for the indication of left ventricular opacification and enhanced endocardial border delineation. The use of contrast enables acquisition of ultrasound images of improved quality. The technique is especially useful in obese patients and those with lung disease. Patients in these categories comprise approximately 10% to 20% of routine echocardiographic examinations. Stress echocardiography examinations can be even more challenging, as the image acquisition time factor is critically important for accurate detection of coronary disease. Improvements in image quality with intravenous contrast agents can facilitate image acquisition and enhance delineation of regional wall motion abnormalities at the peak level of exercise. Recent phase III clinical trial data on the use of Optison and several other agents (currently under evaluation) have revealed that for approximately half of patients, image quality substantively improves, which enables the examination to be salvaged and/or increases diagnostic accuracy. For the "difficult-to-image" patient, this added information results in (1) enhanced laboratory efficiency, (2) a reduction in downstream testing, and (3) possible improvements in patient outcome. In addition, substantial research efforts are underway to use ultrasound contrast agents for assessment of myocardial perfusion. The detection of myocardial perfusion during echocardiographic examinations will permit the simultaneous assessment of global and regional myocardial structure, function, and perfusion-all of the indicators necessary to enable the optimal noninvasive assessment of coronary artery disease. Despite the added benefit in improved efficacy of testing, few data exist regarding the long-term effectiveness of these agents. Currently under evaluation are the clinical and economic outcome implications of intravenous contrast agent use for daily clinical decision making in a variety of patient subsets. Until these data are known, this document offers a preliminary synthesis of available evidence on the value of intravenous contrast agents for use in rest and stress echocardiography. At present, it is the position of this guideline committee that intravenous contrast agents demonstrate substantial value in the difficult-to-image patient with comorbid conditions limiting an ultrasound evaluation of the heart. For such patients, the use of intravenous contrast agents should be encouraged as a means to provide added diagnostic information and to streamline early detection and treatment of underlying cardiac pathophysiology. As with all new technology, this document will require updates and revisions as additional data become available.

Myocardial perfusion by contrast echocardiography: diagnosis of coronary artery disease using contrast-enhanced stress echocardiography and assessment of coronary anatomy and flow reserve.

The advent of intravenous contrast agents, and newer ultrasound technology to enhance their detection, promises to improve and augment our conventional stress echocardiographic practice by improving diagnostic accuracy and providing novel information regarding myocardial perfusion and functional assessment of the coronary vasculature. The combination of intravenous contrast and harmonic stress echocardiography is a powerful tool for improved wall motion analysis through enhanced image quality, routinely permitting the evaluation of patients with suboptimal images. In this era of cost containment, we await studies in large populations addressing resource utilization and cost-effectiveness to determine if, indeed, all patients presenting with stress echocardiography should receive contrast. Myocardial perfusion can be observed using the technique, but the complex interactions of microbubbles and ultrasound in patients must be understood more fully before its implementation becomes routine practice. Non-invasive imaging of coronary arteries using contrast-enhanced transthoracic harmonic echo/Doppler promises to expand the field of diagnostic and experimental echocardiography, bringing new insight into the pathophysiology of ischemic and non-ischemic heart disease. The continued development of newer contrast agents and refinement of ultrasound imaging equipment ensures that the applications of contrast echocardiography in the assessment of CAD will continue to increase.

Contrast echocardiography 1996. A review.

Remarkable advances in the field of contrast echocardiography have been made during the last decade. Interest in ultrasound contrast agents that strengthen the backscattered ultrasound signal and improve image display has stimulated further research. Echocardiographic contrast agents providing left ventricular cavity image enhancement after intravenous injection are now available. A role for contrast echocardiography in the assessment of myocardial perfusion has been established within the invasive clinical setting. With the development of newer contrast agents and new ultrasound technology, myocardial perfusion imaging using contrast echocardiography after venous injection is no longer the unattainable "holy grail," but is fast approaching clinical applicability.