Relative importance of patient, procedural and anatomic risk factors for early vein graft thrombosis after coronary artery bypass graft surgery.

AIM: The aim of the present study was to investigate the relative importance of a wide array of patient demographic, procedural, anatomic and perioperative variables as potential risk factors for early saphenous vein graft (SVG) thrombosis after coronary artery bypass graft (CABG) surgery. METHODS: The patency of 611 SVGs in 291 patients operated on at four different hospitals enrolled in the Reduction in Graft Occlusion Rates (RIGOR) study was assessed six months after CABG surgery by multidetector computed tomography coronary angiography or clinically-indicated coronary angiography. The odds of graft occlusion versus patency were analyzed using multilevel multivariate logistic regression with clustering on patient. RESULTS: SVG failure within six months of CABG surgery was predominantly an all-or-none phenomenon with 126 (20.1%) SVGs totally occluded, 485 (77.3%) widely patent and only 16 (2.5%) containing high-grade stenoses. Target vessel diameter ≤ 1.5 mm (adjusted OR 2.37, P=0.003) and female gender (adjusted OR 2.46, P=0.01) were strongly associated with early SVG occlusion. In a subgroup analysis of 354 SVGs in which intraoperative graft blood flow was measured, lower mean flow was also significantly associated with SVG occlusion when analyzed as a continuous variable (adjusted OR 0.984, P=0.006) though not when analyzed dichotomously, <40 mL/min versus ≥ 40 mL/min (adjusted OR 1.86, P=0.08). CONCLUSION: Small target vessel diameter, female gender and low mean graft blood flow are significant risk factors for SVG thrombosis within six months of CABG surgery in patients on postoperative aspirin therapy. This information may be useful in guiding revascularization strategies in selected patients.

Effect of anti-platelet factor-4/heparin antibody induction on early saphenous vein graft occlusion after coronary artery bypass surgery.

BACKGROUND: Antibodies to complexes of heparin and platelet factor 4 (PF4) are capable of causing heparin-induced thrombocytopenia (HIT). Recent evidence suggests that anti-PF4/heparin antibodies may be prothrombogenic even in the absence of thrombocytopenia and clinically-recognized HIT. OBJECTIVES: To determine if induction of anti-PF4/heparin antibodies is an independent risk factor for early saphenous vein graft (SVG) occlusion or adverse clinical outcome after coronary artery bypass graft (CABG) surgery. PATIENTS/METHODS: Anti-PF4/heparin antibody titers were measured in 368 patients prior to and then 4 days, 6 weeks and 6 months after CABG surgery. Serotonin release assay (SRA) and antibody isotype analysis were also performed on 6-week samples. SVG patency was determined in 297 patients 6 months after surgery by multidetector computed tomography coronary angiography. RESULTS: Six weeks after surgery, 52% of patients were anti-PF4/heparin seropositive and 9% were SRA positive. Six months after surgery, neither the percentage of occluded SVG (19% vs. 20%, P = NS), the percentage of patients with an occluded SVG (33% vs. 33%, P = NS) nor the incidence of adverse clinical events (21% vs. 24%, P = NS) differed between seropositive and seronegative groups. Neither IgG isotype nor SRA positivity was additionally predictive of SVG occlusion or adverse clinical outcome. CONCLUSION: Induction of anti-PF4/heparin antibodies, even those capable of heparin-dependent platelet activation, is not independently associated with early SVG occlusion or adverse clinical outcomes after CABG surgery.

Non-invasive half millimetre 32 detector row computed tomography angiography accurately excludes significant stenoses in patients with advanced coronary artery disease and high calcium scores.

OBJECTIVE: To show an overall diagnostic accuracy > or = 90% for detection of > or = 50% stenoses by coronary half millimetre 32 detector row computed tomography angiography (32 x 0.5-MDCTA) in patients with advanced coronary artery disease (CAD) and a high likelihood of raised calcium scores. METHODS: ECG gated 32 x 0.5-MDCTA (32 x 0.5 mm cross sections, 0.35 x 0.35 x 0.35 mm3 isotropic voxels, 400 ms rotation) was performed after injection of iodixanol (120 ml, 320 mg/ml) in 30 consecutive patients (25 men, mean (SD) age 59 (13) years, body mass index 26.2 (4.9) kg/m2). Native arteries, including > or = 1.5 mm branches, and bypass grafts were screened for > or = 50% stenoses. Stents were excluded. Conventional coronary angiography (performed 18 (12) days before 32 x 0.5-MDCTA) was analysed by quantitative coronary angiography. RESULTS: Median Agatston calcium score was 510 (range 3-5066). Sensitivity, specificity, and positive and negative predictive values for detection of > or = 50% stenoses in native arteries were 76% (29 of 38), 94% (190 of 202), 71% (29 of 41), and 96% (190 of 199), respectively. Overall diagnostic accuracy was 91% (219 of 240). Due to the following artefacts 20% (69 of 352) of the vessels were excluded: motion, noise, and low contrast enhancement isolated or in combination (45 of 69 (65%)); image distortion by implantable cardioverter-defibrillator or pacemaker leads (18 of 69 (26%)); and blooming secondary to severe calcification (6 of 69 (9%)). CONCLUSIONS: Coronary 32 x 0.5-MDCTA accurately excludes > or = 50% stenoses in patients with advanced CAD and high calcium scores with an overall diagnostic accuracy of 91%.

Exercise effects on cardiac size and left ventricular diastolic function: relationships to changes in fitness, fatness, blood pressure and insulin resistance.

OBJECTIVES: To determine exercise training effects on cardiac size and left ventricular (LV) diastolic function and relationships of exercise induced changes in physiological and body composition parameters with cardiac parameters. DESIGN: Prospective, randomised controlled trial. SUBJECTS: Men and women (63.6 (5.7) years, body mass index 29.5 (4.4) kg/m(2)) with untreated hypertension (systolic blood pressure (BP) 130-159 or diastolic BP 85-99 mm Hg). MAIN OUTCOME MEASURES: Cardiac size and LV diastolic function, peak oxygen uptake (Vo(2)), muscle strength, general and abdominal fatness, and insulin resistance. INTERVENTIONS: 6 months of exercise training versus usual care. RESULTS: When analysed by group at six months, cardiac size and LV diastolic function did not differ between exercisers (n = 51) and controls (n = 53), whereas exercisers had significantly higher peak Vo(2) (28 v 24 ml/kg/min) and strength (383 v 329 kg), and lower fatness (34% v 37%), diastolic BP (73 v 75 mm Hg) and insulin resistance (quantitative insulin sensitivity check index 0.35 v 0.34) versus controls (all p

Exercise blood pressure response is related to left ventricular mass.

An exaggerated SBP response to exercise has been associated with increased left ventricular (LV) mass in some but not all studies. A total of 43 women and 34 men, aged 55-75 years, without evidence of cardiovascular disease, with a mean resting BP of 142+/-9/77+/-8 mmHg had their BP measured at rest and during maximal treadmill exercise. LV mass was measured using magnetic resonance imaging. LV mass was adjusted for lean body mass, which was assessed by dual energy X-ray absorptiometry. LV mass was within the normal range for the majority of the subjects. Among the resting and exercise BP indices, maximal SBP was the strongest correlate of LV mass (r=0.41, P<0.05). In multivariate analysis, maximal SBP was independently associated with LV mass after adjustment for lean body mass and gender, explaining 3% of the variance (P<0.05). Maximal exercise SBP is a modest but still independent predictor of LV mass in older persons with normal LV mass. These results raise the possibility that the SBP response to maximal exercise is an early marker of LV hypertrophy.

[Comparative morphofunctional characteristics of the ovaries in women of reproduction age in the norm and with chronic anovulatory infertility]. / Sravnitel'naia morfofunktsional'naia kharakteristika iaichnikov zhenshchin reproductivnogo vozrasta v norme i pri khronicheskom anovuliatornom besplodii.

This work was aimed at the study of ovarian histophysiology in patients with chronic anovulation. The biopsy specimens obtained by endoscopic laparoscopy from the ovaries of women of reproductive age with anovulation or normal cycle (control) were examined. It was found that in the ovaries of anovulation patients the thickness of both tunica albuginea and follicular theca externa was increased. The number of primordial follicles was not different in groups studied, while the number of antral follicles was decreased in anovulation group. No differences in 3 beta-hydroxysteroiddehydrogenase and NADH-dehydrogenase activities in the cells of theca interna and cyst walls were found in both groups, while NADPH-dehydrogenase and NO-synthase activities in these structures were reduced in anovulation. Reduction of estradiol concentration and increase of testosterone concentration were noted in blood of women with anovulatory infertility. The data obtained can be used for the analysis of etiology and pathogenesis of anovulatory infertility and for development of the methods of its treatment.

MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau.

Most noninvasive measures of diastolic function are made during left ventricular (LV) filling and are therefore subject to "pseudonormalization," because variation in left atrial (LA) pressure may confound the estimation of relaxation rate. Counterclockwise twist of the LV develops during ejection, but untwisting occurs rapidly during isovolumic relaxation, before mitral opening. We hypothesized that the rate of untwisting might reflect the process of relaxation independent of LA pressure. Recoil rate (RR), the velocity of LV untwisting, was measured by tagged magnetic resonance imaging and regressed against the relaxation time constant (tau), recorded by catheterization, in 10 dogs at baseline and after dobutamine, saline, esmolol, and methoxamine treatment. RR correlated closely (average r = -0.86) with tau and was unaffected by elevated LA pressure. Multiple regression showed that tau, but not LA or aortic pressure, was an independent predictor of RR (P < 0.0001, P = 0.99, and P = 0.18, respectively). The rate of recoil of torsion, determined wholly noninvasively, provides an isovolumic phase, preload-independent assessment of LV relaxation. Use of this novel parameter should allow the detailed study of diastolic function in states known to affect filling rates, such as aging, hypertension, and congestive heart failure.

Improved arterial compliance by a novel advanced glycation end-product crosslink breaker.

BACKGROUND: Arterial stiffening with increased pulse pressure is a leading risk factor for cardiovascular disease in the elderly. We tested whether ALT-711, a novel nonenzymatic breaker of advanced glycation end-product crosslinks, selectively improves arterial compliance and lowers pulse pressure in older individuals with vascular stiffening. METHODS AND RESULTS: Nine US centers recruited and randomly assigned subjects with resting arterial pulse pressures >60 mm Hg and systolic pressures >140 mm Hg to once-daily ALT-711 (210 mg; n=62) or placebo (n=31) for 56 days. Preexisting antihypertensive treatment (90% of subjects) was continued during the study. Morning upright blood pressure, stroke volume, cardiac output, systemic vascular resistance, total arterial compliance, carotid-femoral pulse wave velocity, and drug tolerability were assessed. ALT-711 netted a greater decline in pulse pressures than placebo (-5.3 versus -0.6 mm Hg at day 56; P=0.034 for treatment effect by repeated-measures ANOVA). Systolic pressure declined in both groups, but diastolic pressure fell less with ALT-711 (P=0.056). Mean pressure declined similarly in both groups (-4 mm Hg; P<0.01 for each group, P=0.34 for treatment effect). Total arterial compliance rose 15% in ALT-711-treated subjects versus no change with placebo (P=0.015 versus ALT-711), an effect that did not depend on reduced mean pressure. Pulse wave velocity declined 8% with ALT-711 (P<0.05 at day 56, P=0.08 for treatment effect). Systemic arterial resistance, cardiac output, and heart rate did not significantly change in either group. CONCLUSIONS: ALT-711 improves total arterial compliance in aged humans with vascular stiffening, and it may provide a novel therapeutic approach for this abnormality, which occurs with aging, diabetes, and isolated systolic hypertension.

Attenuated myocardial vasodilator response in patients with hypertensive hypertrophy revealed by oxygenation-dependent magnetic resonance imaging.

BACKGROUND: Oxygen (O(2)) homeostasis is central to myocardial tissue functioning, and increased O(2) demand is thought to be satisfied by a vasodilatory mechanism that results in increased blood and O(2) delivery. We applied blood oxygenation level-dependent (BOLD) MRI in conjunction with vasodilatory stress to index the ability to augment intramyocardial oxygenation in hypertensive hypertrophy, the primary cause of heart failure. METHODS AND RESULTS: Nine healthy controls and 10 hypertensive subjects with moderate-to-severe hypertrophy underwent imaging on a 1.5 T clinical scanner. The dipyridamole-induced change in the apparent transverse relaxation rate, R2*, which correlates with hemoglobin oxygenation, was -5.4+/-2.2 s(-1) (95% CI, -4.0 to -6.8 s(-1)) in controls compared with -1.7+/-1.4 s(-1) (95% CI, -0.8 to -2.6 s(-1)) in hypertensive patients (P=0.0003). CONCLUSIONS: Patients with hypertensive hypertrophy demonstrate an impaired ability to increase intramyocardial oxygenation during vasodilatory stress, as indexed by BOLD MRI. The capacity to image vascular function with BOLD MRI may advance the understanding of the development of ventricular dysfunction in hypertension.

Transesophageal echocardiographic findings in subcortical and cortical stroke.

Historically, subcortical stroke is believed to be secondary to intracranial small vessel disease. In this study, transesophageal echocardiographic findings such as aortic atherosclerotic disease and other potential cardiac sources of emboli were common in patients with subcortical stroke, supporting a multifactorial etiology for subcortical stroke and a role for transesophageal echocardiography in this patient population.

Independent effects of preload, afterload, and contractility on left ventricular torsion.

Shortening of oblique left ventricular (LV) fibers results in torsion. A unique relationship between volume and torsion is therefore expected, and the effects of load and contractility on torsion should be predictable. However, volume-independent behavior of torsion has been observed, and the effects of load on this deformation remain controversial. We used magnetic resonance imaging (MRI) with tagging to study the relationships between load and contractility, and torsion. In ten isolated, blood-perfused canine hearts, ejection was controlled by a servopump: end-diastolic volume (EDV) was controlled by manipulating preload parameters and end-systolic volume (ESV) by manipulating afterload using a three-element windkessel model. MRI was obtained at baseline, two levels of preload alteration, two levels of afterload alteration, and dobutamine infusion. An increase in EDV resulted in an increase in torsion at constant ESV (preload effect), whereas an increase in ESV resulted in a decrease in torsion at constant EDV (afterload effect). Dobutamine infusion increased torsion in association with an increase in LV peak-systolic pressure (PSP), even at identical EDV and ESV. Multiple regression showed correlation of torsion with preload (EDV), afterload (ESV), and contractility (PSP; r = 0.67). Furthermore, there was a close linear relationship between torsion and stroke volume (SV) and ejection fraction (EF) during load alteration, but torsion during dobutamine infusion was greater than expected for the extent of ejection. Preload and afterload influence torsion through their effects on SV and EF, and there is an additional direct inotropic effect on torsion that is independent of changes in volume but rather is force dependent. There is therefore potential for the torsion-volume relation to provide a load-independent measure of contractility that could be measured noninvasively.

Safety and efficacy of weight training soon after acute myocardial infarction.

BACKGROUND: To determine if weight training used during cardiac rehabilitation as soon as 4 weeks after myocardial infarction (MI) is safe, and if weight training combined with aerobic exercise improves aerobic fitness and muscle strength more than aerobic exercise alone. METHODS: Twenty-three men within 6 weeks of an acute MI and without exercise-induced ischemia, complex arrhythmias, anterior Q wave MI, or ejection fraction < 40% were randomly assigned to combined weight and cycle training versus cycle training for 10 weeks. The main measures were change in maximal oxygen uptake (VO2max), muscle strength, resting left ventricular (LV) wall segment motion and early diastolic filling by resting echocardiograms, exercise ECG, heart rate, and blood pressure responses [corrected]. RESULTS: VO2max increased 14% (P < 0.01) and cycle time increased 10% (P < 0.01) in the combined training group. The 8% increases in VO2max (P = 0.15) and cycle time (P = 0.08) in the cycling group were not significant. Arm and leg strength increased (P < 0.01) in each group. However, the change was greater for the combined training group--31% versus 16% (P < 0.03) for leg strength and 20% versus 10% (P < 0.001) for arm strength. There were no changes for either group in resting hemodynamics, body weight and composition, LV wall segment motion, LV fractional shortening, and early diastolic function, and no adverse clinical events or exercise-related complications. CONCLUSIONS: Combined training soon after MI improved aerobic and muscle fitness more than cycling alone, and was performed without complication.

Noninvasive measurement of shortening in the fiber and cross-fiber directions in the normal human left ventricle and in idiopathic dilated cardiomyopathy.

BACKGROUND: Studies in anesthetized dogs have shown that myocardial fibers shorten approximately 8%. However, in the endocardium, shortening occurs to a much greater extent at 90 degrees to the fiber orientation ("cross-fiber shortening") than it does along the fiber direction. The purpose of this study was to estimate the extent of fiber and cross-fiber shortening in the normal human left ventricle and in patients with idiopathic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Ten normal subjects and nine patients with IDC were imaged with magnetic resonance tissue tagging. Finite strain analysis was used to calculate endocardial and epicardial shortening in the fiber and cross-fiber directions using anatomic fiber angles from representative autopsy specimens as references. Anatomic fiber angles were not different between normal subjects and IDC patients. Epicardial fiber strain was -0.14+/-0.01 in normal subjects and -0.08+/-0.01 in IDC patients (P<.0001 versus normal subjects). Epicardial cross-fiber strain was -0.08+/-0.01 in normal subjects and -0.06+/-0.01 in IDC patients (P=NS). Endocardial fiber strain was -0.16+/-0.01 in normal subjects and -0.09+/-0.01 in IDC patients (P<.0001), and endocardial cross-fiber strain was -0.26+/-0.01 in normal subjects and -0.15+/-0.01 in IDC patients (P<.0001). Cross-fiber shortening was greater than fiber shortening at the endocardium in both normal subjects (P<.0001) and IDC patients (P<.05). CONCLUSIONS: In normal humans, the direction of maximal deformation aligns with the fiber direction in the epicardium but is perpendicular to the fiber direction in the endocardium. When strain in a coordinate system aligned to the fibers is estimated, cross-fiber shortening is found to be the dominant shortening strain at the endocardium. Normal fiber shortening is 15%, and this is markedly reduced in IDC. The normal transition in fiber orientation through the wall is not altered in IDC, and cross-fiber shortening is still the dominant strain at the endocardium, suggesting that interactions between myocardial layers persist in these patients.

Localization of ischemia in canine hearts using tagged rotated long axis MR images, endocardial surface stretch and wall thickening.

Tagged magnetic resonance imaging allows the noninvasive measurement of regional systolic myocardial deformations and helps localize ischemic regions in the left ventricle (LV). The objective of this study was to evaluate the potential accuracy of localizing ischemic regions in the LV using endocardial and epicardial data obtained from tagged rotated long axis images. Nine canine hearts with acute ischemia induced by coronary artery ligation were imaged along four long axis planes rotated around the LV long axis, at end diastole and end systole. Each plane was tagged by four parallel lines perpendicular to the LV long axis. Tracing the endocardial and epicardial intersection points of the tag lines, 24 myocardial cuboids were reconstructed for each LV at end diastole and end systole. Endocardial surface stretch and transmural systolic thickening were calculated for each cuboid. The functional data were compared to perfusion data obtained from postmortem monastral blue staining of the heart. The ability of each functional index to discriminate between ischemic and non-ischemic regions was assessed using the "t"-statistic. The potential accuracy in localizing ischemia was evaluated by studying the corresponding sensitivity-specificity curves. The results demonstrate that adequate discrimination and localization can be obtained with both functional indices. However, endocardial surface stretch is advantageous as it uses only endocardial data and can save 50% of the post-processing time.

In vivo assessment of regional myocardial work in normal canine hearts using 3D tagged MRI.

A non-invasive method for assessing regional myocardial work is presented. The method utilizes tagged magnetic resonance images (MRI) obtained from two sets of orthogonal planes to mark and reconstruct 24 small myocardial cuboids at end-diastole (ED) and end-systole (ES) in the in vivo left ventricle (LV). Regional myocardial work is assessed by calculating the area enclosed by the endocardial wall tension-area (T-A) loop of each studied cuboid. The method was applied to six normal canine hearts. In addition, a global myocardial work index was obtained from the corresponding estimated pressure-volume (P-V) loops. The average work index calculated using the T-A loop was 0.242 +/- 0.088 J/100gr/beat, in agreement with the average index obtained from the P-V loop: 0.296 +/- 0.089 J/100gr/beat. The two indices correlate linearly with a correlation coefficient of 0.82.

Age-associated changes in left ventricular outflow tract geometry in normal subjects.

This study examined age-associated changes in the geometry of the left ventricular outflow tract in normal subjects using Doppler echocardiography. With advancing age, the angle between the interventricular septum and the aortic root became more acute and a discrete bulging of the proximal septum was more common, but neither finding appeared to affect resting outflow tract velocity or left ventricular mass significantly.

Three-dimensional mapping of acute ischemic regions using artificial neural networks and tagged MRI.

Many methods for mapping ischemic myocardial regions by functional analysis have been suggested. However, the complicated relationship between myocardial function and perfusion, and the inherent limitations of the imaging techniques used, have led to a generally low mapping accuracy. We show herein, that highly accurate mapping can be obtained by combining tagged magnetic resonance imaging (MRI), three-dimensional (3-D) analysis, and artificial neural networks. Nine canine hearts with acute ischemia were studied using multiplanar tagged MRI. Twenty-four myocardial cuboids were tagged in each heart and reconstructed in 3-D at end diastole (ED) and end systole (ES). The cuboids were arranged in three slices approximately 1 cm thick and covered most of the left ventricle (LV). Transmural thickening and endocardial area strain were calculated for each cuboid. Applying a post-mortem (PM) analysis, the percent ischemia in each cuboid was estimated using monastral blue dye; the PM analysis served as a "gold standard." An artificial neural network (ANN), designed to estimate the percent ischemia in each cuboid from the functional indexes, was then created. The ANN "learned" the function-ischemia relationship in 192 cuboids taken from eight of the hearts and was asked to estimate the percent ischemia in the 24 cuboids of the ninth heart. The process was repeated nine times, each time using a different heart as test case. The average accuracy of mapping, i.e., the accuracy with which the ANN has mapped the normal and ischemic cuboids using the functional parameters, was 87.5% +/- 7.8 (s.d.). This accuracy was superior to the accuracy obtained by optimal thresholding of the same thickening (80.1%) and endocardial strain (76.9%) data.

Effects of afterload on regional left ventricular torsion.

OBJECTIVE: To determine if left ventricular torsion, as measured by magnetic resonance tissue tagging, is afterload dependent in a canine isolated heart model in which neurohumoral responses are absent, and preload is constant. METHODS: In ten isolated, blood perfused, ejecting, canine hearts, three afterloads were studied, while keeping preload constant: low afterload, high afterload (stroke volume reduced by approx. 50% of low afterload), and isovolumic loading (infinite afterload). RESULTS: There were significant effects of afterload on both torsion (P < 0.05) and circumferential shortening (P < 0.0005). Between low and high afterloads, at the anterior region of the endocardium only, where torsion was maximal, there was a significant reduction in torsion (15.1 +/- 2.2 degrees to 7.8 +/- 1.8 degrees, P < 0.05). Between high afterload and isovolumic loading there was no significant change in torsion (7.8 +/- 1.8 degrees to 6.2 +/- 1.5 degrees, P = NS). Circumferential shortening at the anterior endocardium was significantly reduced both between low and high afterload (-0.19 +/- 0.02 to -0.11 +/- 0.02, P < 0.0005), and also between high afterload and isovolumic loading (-0.11 +/- 0.02 to 0.00 +/- 0.02, P < 0.05). Plots of strains with respect to end-systolic volume demonstrated a reduction in both torsion and shortening with afterload-induced increases in end-systolic volume. Torsion, but not circumferential shortening, persisted at isovolumic loading. CONCLUSIONS: Maximal regional torsion of the left ventricle is afterload dependent. The afterload response of torsion appears related to the effects of afterload on end-systolic volume.