Search PubMed⌕ Search

Biomedical subjects

Warren J Manning

Publications and source records attributed to Warren J Manning.

At least 55 records · Page 3Linked to original sources
PubMed2004

Association of aortic valve calcium detected by electron beam computed tomography with echocardiographic aortic valve disease and with calcium deposits in the coronary arteries and thoracic aorta.

We conducted electron beam computed tomographic (EBCT) testing in a representative sample of 327 Framingham Heart Study subjects without clinical cardiovascular disease. EBCT was compared with 2-dimensional echocardiography for the detection of degenerative aortic valve (AV) disease. We determined the association between EBCT measures of AV calcium and calcium deposits in the coronary arteries and thoracic aorta. Of 327 subjects (mean age 60 +/- 9 years; 51% men), 14% had EBCT AV calcium (median Agatston score 0, range 0 to 1,592). The prevalence of AV calcium increased predictably across decades of age. Compared with echocardiography, the sensitivity and specificity of EBCT for the detection of degenerative AV disease were 24% and 94%, respectively. In unadjusted logistic regression models, the prevalence of EBCT AV calcium increased across tertiles of coronary artery calcium (for trend across tertiles, odds ratio [OR] 2.2, 95% confidence interval [CI] 1.4 to 3.5) and thoracic aorta calcium (for trend OR 2.8, 95% CI 1.7 to 4.4). After adjustment for age and gender, the associations of AV calcium with coronary calcium and thoracic aorta calcium were attenuated and no longer statistically significant. Thus, compared with echocardiography, EBCT was specific but insensitive for the detection of degenerative AV disease. EBCT AV calcium was associated with calcium deposits in the coronary arteries and the thoracic aorta, but these associations were confounded by age and risk factors.

Aged↗
PubMed2004

Spiral MR myocardial tagging.

In the present study, complementary spatial modulation of magnetization (CSPAMM) myocardial tagging was extended with an interleaved spiral imaging sequence. The use of a spiral sequence enables the acquisition of grid-tagged images with a tagline distance as low as 4 mm in a single breath-hold. Alternatively, a high temporal resolution of 77 frames per second was obtained with 8-mm grid spacing. Ten healthy adult subjects were studied. With this new approach, high-quality images can be obtained and the tags persist throughout the entire cardiac cycle.

Adult↗
PubMed2004

Assessment of left atrial volume by contrast enhanced magnetic resonance angiography.

Left atrial (LA) volume is associated with cardiovascular morbidity, particularly atrial fibrillation. Contrast-enhanced magnetic resonance angiography (CE-MRA) visualizes the LA, but the validity of LA volume measurements using this technique has not been evaluated. We performed CE-MRA and cine magnetic resonance (MR) in 18 consecutive patients referred for CE-MRA prior to atrial fibrillation ablation. The CE-MRA LA volumes were compared to cine MR LA volumes at the maximal LA size and at LA end-diastole using linear regression and limits of agreement analysis. The mean cine MR LA volume was 118 +/- 39 mL at maximal LA size and 91 +/- 38 mL at LA end-diastole. Left atrial volume determined by CE-MRA was 93 +/- 38 mL. Although the CE-MRA LA volume had a strong correlation with the maximal cine MR LA volume (R2 = 0.86, p < 0.001), the 95% limits of agreement were relatively wide (-54 to 3 mL). The cine MR LA end-diastolic and CE-MRA LA volumes were more closely correlated (R2 = 0.98, p < 0.001) with narrow 95% limits of agreement (-8 to 11 mL). The CE-MRA LA volumes correspond most closely to LA end-diastolic cine MR LA volumes and may be a useful measure of LA size.

Cardiac Volume↗
PubMed2004

A method for the determination of proximal pulmonary vein size using contrast-enhanced magnetic resonance angiography.

OBJECTIVES: We sought to develop a reproducible method for characterizing the anatomy of the proximal pulmonary veins. BACKGROUND: Contrast-enhanced three-dimensional magnetic resonance angiography (CE-MRA) is a commonly requested test before and after radiofrequency ablation for the treatment of atrial fibrillation. While CE-MRA readily visualizes the pulmonary veins, there is no standardized method for determining their size and cross-sectional anatomy. METHODS: Data for 24 consecutive patients referred for pulmonary vein CE-MRA before an elective ablation procedure for the treatment of atrial fibrillation were analyzed. Detailed measurements of the pulmonary vein diameter, circumference, and cross-sectional area were obtained at three locations: the juncture of the pulmonary vein with the left atrium (LA) (position 1J), the narrowest segment within 5 mm of the juncture (position 2(5mm)), and at the location in the sagittal plane at which the pulmonary veins separate from the LA and from each other (position 3Sag). Intraobserver and interobserver variabilities were also determined for each method. RESULTS: The left lower pulmonary vein was significantly smaller than the other pulmonary veins at positions 1J and 2(5mm) (p<0.05). The right upper pulmonary vein was significantly larger than the other pulmonary vein at position 3Sag (p<0.05). At positions 1J and 2(5mm), the diameter had a low correlation with the circumference and cross-sectional area. At position 3Sag, the major and minor axis dimensions had a very high correlation with the circumference and cross-sectional area. The intraobserver and interobserver variabilities were substantially lower (better) for position 3Sag. CONCLUSIONS: Pulmonary vein diameter measurements are highly variable and do not reflect true anatomic variation in cross-sectional anatomy. A sagittal method of determining pulmonary vein size was highly reproducible and may therefore be advantageous for use in patients likely to need serial examinations.

Adult↗
PubMed2004

Association between ghrelin and cardiovascular indexes in healthy obese and lean men.

OBJECTIVE: Obesity is an increasingly common condition and is associated with excess morbidity and mortality, including clinical and subclinical cardiac dysfunction. The role of hormones involved in energy homeostasis, including ghrelin and leptin, in cardiovascular function remains incompletely understood. Therefore, we sought to evaluate the association between systemic ghrelin and leptin levels with indexes of cardiovascular structure and function. DESIGN AND MEASUREMENTS: We measured serum ghrelin and leptin levels in 25 clinically healthy obese men and 25 lean controls, using commercially available immunoassays. We also assessed right and left ventricular structure and function using cardiac magnetic resonance imaging. We then investigated the association between serum ghrelin and leptin levels with cardiac indexes, using univariate and multivariate analysis. RESULTS: There was an independent association between serum ghrelin levels and height-adjusted right ventricular mass (r = -0.324, P = 0.026), right ventricular end-diastolic volume (r = -0.363, P = 0.017) and right ventricular end-systolic volume (r = -0.398, P = 0.009) as well as right ventricular ejection fraction (r = 0.317, P = 0.050). There was no significant association between serum ghrelin and indexes of left ventricular structure or function. We also identified an association between serum leptin levels and resting heart rate (r = 0.391, P = 0.002). There was an association between serum leptin and height-adjusted left ventricular mass on univariate, but not on multivariate, analysis. CONCLUSIONS: Serum ghrelin is associated with right ventricular cardiovascular indexes and serum leptin is associated with resting heart rate. These associations indicate a close interaction between the endocrine and cardiovascular systems in obesity.

Adult↗
PubMed2004

Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range, 2.0 to 3.0): In patients with persistent or paroxysmal AF (PAF) [intermittent AF] at high risk of stroke (ie, having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, age > 75 years, moderately or severely impaired left ventricular systolic function and/or congestive heart failure, history of hypertension, or diabetes mellitus), we recommend anticoagulation with an oral VKA, such as warfarin (Grade 1A). In patients with persistent AF or PAF, age 65 to 75 years, in the absence of other risk factors, we recommend antithrombotic therapy with either an oral VKA or aspirin, 325 mg/d, in this group of patients who are at intermediate risk of stroke (Grade 1A). In patients with persistent AF or PAF < 65 years old and with no other risk factors, we recommend aspirin, 325 mg/d (Grade 1B). For patients with AF and mitral stenosis, we recommend anticoagulation with an oral VKA (Grade 1C+). For patients with AF and prosthetic heart valves, we recommend anticoagulation with an oral VKA (Grade 1C+); the target INR may be increased and aspirin added depending on valve type and position, and on patient factors. For patients with AF of > or = 48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA for 3 weeks before and for at least 4 weeks after successful cardioversion (Grade 1C+). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacologic or electrical cardioversion, an alternative strategy is anticoagulation and screening multiplane transesophageal echocardiography (Grade 1B). If no thrombus is seen and cardioversion is successful, we recommend anticoagulation for at least 4 weeks (Grade 1B). For patients with AF of known duration < 48 h, we suggest cardioversion without anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or low molecular weight heparin at presentation (Grade 2C).

Aged↗
PubMed2004

Coronary MR angiography: comparison of quantitative and qualitative data from four techniques.

OBJECTIVE: The optimal coronary MR angiography sequence has yet to be determined. We sought to quantitatively and qualitatively compare four coronary MR angiography sequences. SUBJECTS AND METHODS. Free-breathing coronary MR angiography was performed in 12 patients using four imaging sequences (turbo field-echo, fast spin-echo, balanced fast field-echo, and spiral turbo field-echo). Quantitative comparisons, including signal-to-noise ratio, contrast-to-noise ratio, vessel diameter, and vessel sharpness, were performed using a semiautomated analysis tool. Accuracy for detection of hemodynamically significant disease (> 50%) was assessed in comparison with radiographic coronary angiography. RESULTS: Signal-to-noise and contrast-to-noise ratios were markedly increased using the spiral (25.7 +/- 5.7 and 15.2 +/- 3.9) and balanced fast field-echo (23.5 +/- 11.7 and 14.4 +/- 8.1) sequences compared with the turbo field-echo (12.5 +/- 2.7 and 8.3 +/- 2.6) sequence (p < 0.05). Vessel diameter was smaller with the spiral sequence (2.6 +/- 0.5 mm) than with the other techniques (turbo field-echo, 3.0 +/- 0.5 mm, p = 0.6; balanced fast field-echo, 3.1 +/- 0.5 mm, p < 0.01; fast spin-echo, 3.1 +/- 0.5 mm, p < 0.01). Vessel sharpness was highest with the balanced fast field-echo sequence (61.6% +/- 8.5% compared with turbo field-echo, 44.0% +/- 6.6%; spiral, 44.7% +/- 6.5%; fast spin-echo, 18.4% +/- 6.7%; p < 0.001). The overall accuracies of the sequences were similar (range, 74% for turbo field-echo, 79% for spiral). Scanning time for the fast spin-echo sequences was longest (10.5 +/- 0.6 min), and for the spiral acquisitions was shortest (5.2 +/- 0.3 min). CONCLUSION: Advantages in signal-to-noise and contrast-to-noise ratios, vessel sharpness, and the qualitative results appear to favor spiral and balanced fast field-echo coronary MR angiography sequences, although subjective accuracy for the detection of coronary artery disease was similar to that of other sequences.

Aged↗
PubMed2003

Ventricular-specific expression of angiotensin II type 2 receptors causes dilated cardiomyopathy and heart failure in transgenic mice.

The angiotensin II type 2 (AT2) receptor is upregulated in the left ventricle in heart failure, but its pathophysiological roles in vivo are not understood. In the present study, AT2 receptors were expressed in transgenic (TG) mice using the ventricular-specific myosin light-chain (MLC-2v) promoter. In TG compared with nontransgenic (NTG) mice, in vivo left ventricular (LV) systolic pressure and peak +dP/dt were depressed while LV diastolic pressure was elevated (P < 0.05). Echocardiography showed severely depressed LV fractional shortening, increased systolic and diastolic dimensions, and wall thinning (P < 0.05). Confocal and electron microscopy studies revealed an increase in the size of myocytes and interstitial spaces as well as an increase in interstitial collagen, disruption of the Z-band, and changes in cytochrome c localization. The changes were most prominent in the highest-expressing TG line, which implies a dose-response relationship. AT2 overexpression was also directly associated with the increase of phosphorylated protein levels of PKC-alpha, PKC-beta, and p70S6 kinase. These data demonstrate that ventricular myocyte-specific expression of AT2 receptors promotes the development of dilated cardiomyopathy and heart failure in vivo.

Animals↗
PubMed2003

Rapamycin attenuates load-induced cardiac hypertrophy in mice.

BACKGROUND: Cardiac hypertrophy, or an increase in heart size, is an important risk factor for cardiac morbidity and mortality. The mammalian target of rapamycin (mTOR) is a component of the insulin-phosphoinositide 3-kinase pathway, which is known to play a critical role in the determination of cell, organ, and body size. METHODS AND RESULTS: To examine the role of mTOR in load-induced cardiac hypertrophy, we administered rapamycin, a specific inhibitor of mTOR, to mice with ascending aortic constriction. Activity of p70 ribosomal S6 kinase 1 (S6K1), an effector of mTOR, was increased by 3.8-fold in the aortic-constricted heart. Pretreatment of mice with 2 mg. kg-1. d-1 of rapamycin completely suppressed S6K1 activation and S6 phosphorylation in response to pressure overload. The heart weight/tibial length ratio of vehicle-treated aortic-banded mice was increased by 34.4+/-3.6% compared with vehicle-treated sham-operated mice. Rapamycin suppressed the load-induced increase in heart weight by 67%. Attenuation of cardiac hypertrophy by rapamycin was associated with attenuation of the increase in myocyte cell size induced by aortic constriction. Rapamycin did not cause loss of body weight, lethality, or left ventricular dysfunction. CONCLUSIONS: mTOR or its target(s) seems to play an important role in load-induced cardiac hypertrophy. Because systemic administration of rapamycin has been used successfully for the treatment of transplant rejection in clinical practice, it may be a useful therapeutic modality to suppress cardiac hypertrophy in patients.

Animals↗
PubMed2003

Comparison of aortic elasticity determined by cardiovascular magnetic resonance imaging in obese versus lean adults.

The vascular properties of large vessels in the obese have not been adequately studied. We used cardiovascular magnetic resonance imaging to quantify the cross-sectional area and elastic properties of the ascending thoracic and abdominal aorta in 21 clinically healthy obese young adult men and 25 men who were age-matched lean controls. Obese subjects had greater maximal cross-sectional area of the ascending thoracic aorta (984 +/- 252 vs 786 +/- 109 mm(2), p <0.01) and of the abdominal aorta (415 +/- 71 vs 374 +/- 51 mm(2), p <0.05). When indexed for height the differences persisted, but when indexed for body surface area, a significant difference between groups was found only for the maximal abdominal aortic cross-sectional area. The obese subjects also had decreased abdominal aortic elasticity, characterized by 24% lower compliance (0.0017 +/- 0.0004 vs 0.0021 +/- 0.0005 mm(2)/kPa/mm, p <0.01), 22% higher stiffness index beta (6.0 +/- 1.5 vs 4.9 +/- 0.7, p <0.005), and 41% greater pressure-strain elastic modulus (72 +/- 25 vs 51 +/- 9, p <0.005). At the ascending thoracic aorta, only the pressure-strain elastic modulus was different between obese and lean subjects (85 +/- 42 vs 65 +/- 26 kPa, respectively; p <0.05), corresponding to a 31% difference-but arterial compliance and stiffness index were not significantly different between groups. In clinically healthy young adult obese men, obesity is associated with increased cross-sectional aortic area and decreased aortic elasticity.

Adult↗
PubMed2003

The impact of spatial resolution and respiratory motion on MR imaging of atherosclerotic plaque.

PURPOSE: To examine the impact of spatial resolution and respiratory motion on the ability to accurately measure atherosclerotic plaque burden and to visually identify atherosclerotic plaque composition. MATERIALS AND METHODS: Numerical simulations of the Bloch equations and vessel wall phantom studies were performed for different spatial resolutions by incrementally increasing the field of view. In addition, respiratory motion was simulated based on a measured physiologic breathing pattern. RESULTS: While a spatial resolution of > or = 6 pixels across the wall does not result in significant errors, a resolution of < or = 4 pixels across the wall leads to an overestimation of > 20%. Using a double-inversion T2-weighted turbo spin echo sequence, a resolution of 1 pixel across equally thick tissue layers (fibrous cap, lipid, smooth muscle) and a respiratory motion correction precision (gating window) of three times the thickness of the tissue layer allow for characterization of the different coronary wall components. CONCLUSIONS: We found that measurements in low-resolution black blood images tend to overestimate vessel wall area and underestimate lumen area.

Arteriosclerosis↗