Feedback and Analysis System to Improve Partial Weight Bearing and Bone Healing Following Fractures and Osteotomies of the Lower Limb: Technical Note.

PURPOSE OF THE STUDY After the surgical treatment of injuries of the lower extremities or osteotomies, patients are frequently asked to partially load the affected leg during the first weeks of rehabilitation. The patient's compliance to the prescribed weight bearing limit and their ability to regain a physiological gait as soon as possible are necessary for a fast rehabilitation without complications. MATERIAL AND METHODS/RESULTS To support patients during this important phase of recovery, we developed a feedback and analysis system that is able to provide feedback concerning loading and roll over behavior to the patient. The system is based on sensor insoles to measure the amount of pressure and pressure distribution and on a smartphone application to provide realtime visual and acoustic feedback. CONCLUSIONS This newly developed device has the potential to monitor the rehabilitation phase and assist patients with lower leg injuries therefore decrease the complication rate and enable faster rehabilitation. Key words: lower limb fracture osteotomy around the knee, partial weight bearing, realtime feedback, smartphone application.

Infective endocarditis on ICU: risk factors, outcome and long-term follow-up.

OBJECTIVE: To identify factors associated with short-term, intermediate and long-term outcome in patients with infective endocarditis (IE) and the need for treatment on intensive care unit (ICU). DESIGN AND SETTING: Retrospective analysis and long-term follow-up by questionnaire in the two medical ICUs of our university hospital. PATIENTS: We conducted a retrospective analysis of all consecutive patients with IE and need for ICU treatment in our department between 2002 and 2009. All patients fulfilled the modified Duke criteria for definite diagnosis of IE. MEASUREMENTS AND MAIN RESULTS: Data of 216 patients (aged 62 ± 14 years, 31 % female) were analyzed, 15.7 % of whom had prosthetic valve endocarditis. Infectious agent (IA) was identified in 74 % and surgery was performed in 57 %. 56 patients (24.9 %) died on ICU, 9 patients were sent to palliative care units and died several days later. During follow-up, another 44 patients died. Multivariate Cox-regression analysis identified the following independent risk factors: High initial SAPS II for 30d-, multiple organ failure and high maximum SAPS II for 100d- and high maximum leukocyte count for long-term mortality. Surgical intervention during ICU was an independent predictor of a better 30d outcome. CONCLUSIONS: In contrast to general IE populations, IA and the type of infected impaired valve are not main predictors of survival in critically ill IE-patients. Biomarker of acute infection and markers for severity of illness (scores and organ failure) are independent risk factors for mortality. The surgical clearance of infected valve, device or abscesses is an independent predictor of 30d outcome.

Comparison between transcatheter and surgical prosthetic valve implantation in patients with severe aortic stenosis and reduced left ventricular ejection fraction.

BACKGROUND: Patients with severe aortic stenosis and reduced left ventricular ejection fraction (LVEF) have a poor prognosis with conservative therapy but a high operative mortality when treated surgically. Recently, transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement (SAVR) for patients considered at high or prohibitive operative risk. The objective of this study was to compare TAVI and SAVR with respect to postoperative recovery of LVEF in patients with severe aortic stenosis and reduced LV systolic function. METHODS AND RESULTS: Echocardiographic data were prospectively collected before and after the procedure in 200 patients undergoing SAVR and 83 patients undergoing TAVI for severe aortic stenosis (aortic valve area ≤1 cm(2)) with reduced LV systolic function (LVEF ≤50%). TAVI patients were significantly older (81±8 versus 70±10 years; P<0.0001) and had more comorbidities compared with SAVR patients. Despite similar baseline LVEF (34±11% versus 34±10%), TAVI patients had better recovery of LVEF compared with SAVR patients (ΔLVEF, 14±15% versus 7±11%; P=0.005). At the 1-year follow-up, 58% of TAVI patients had a normalization of LVEF (>50%) as opposed to 20% in the SAVR group. On multivariable analysis, female gender (P=0.004), lower LVEF at baseline (P=0.005), absence of atrial fibrillation (P=0.01), TAVI (P=0.007), and larger increase in aortic valve area after the procedure (P=0.01) were independently associated with better recovery of LVEF. CONCLUSION: In patients with severe aortic stenosis and depressed LV systolic function, TAVI is associated with better LVEF recovery compared with SAVR. TAVI may provide an interesting alternative to SAVR in patients with depressed LV systolic function considered at high surgical risk.

Pulmonary arterial hypertension in adults with congenital heart disease.

Pulmonary arterial hypertension (PAH) is a common problem in adult patients with congenital heart disease. We review available data on aetiology, clinical presentation, prognosis and management of PAH in this setting. In addition, we discuss general management strategies and emerging disease-targeting therapies.

Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury.

The role of a local angiotensin system in the vascular response to arterial injury was investigated by administering the angiotensin-converting enzyme (CE) inhibitor cilazapril to normotensive rats in which the left carotid artery was subjected to endothelial denudation and injury by balloon catheterization. In control animals, by 14 days after balloon injury, the processes of smooth muscle cell (SMC) proliferation, migration of SMCs from the media to the intima, and synthesis of extracellular matrix produced marked thickening of the intima, with reduction of the cross-sectional area of the lumen. However, in animals that received continuous treatment with the CE inhibitor, neointima formation was decreased (by about 80 percent), and lumen integrity was preserved. Thus, the angiotensin-converting enzyme may participate in modulating the proliferative response of the vascular wall after arterial injury, and inhibition of this enzyme may have therapeutic applications to prevent the proliferative lesions that occur after coronary angioplasty and vascular surgery.

Calcium signalling and pancreatic cell death: apoptosis or necrosis?

Secretagogues, such as cholecystokinin and acetylcholine, utilise a variety of second messengers (inositol trisphosphate, cADPR and nicotinic acid adenine dinucleotide phosphate) to induce specific oscillatory patterns of calcium (Ca(2+)) signals in pancreatic acinar cells. These are tightly controlled in a spatiotemporal manner, and are coupled to mitochondrial metabolism necessary to fuel secretion. When Ca(2+) homeostasis is disrupted by known precipitants of acute pancreatitis, for example, hyperstimulation or non-oxidative ethanol metabolites, Ca(2+) stores (endoplasmic reticulum and acidic pool) become depleted and sustained cytosolic [Ca(2+)] elevations replace transient signals, leading to severe consequences. Sustained mitochondrial depolarisation, possibly via opening of the mitochondrial permeability transition pore (MPTP), elicits cellular ATP depletion that paralyses energy-dependent Ca(2+) pumps causing cytosolic Ca(2+) overload, while digestive enzymes are activated prematurely within the cell; Ca(2+)-dependent cellular necrosis ensues. However, when stress to the acinar cell is milder, for example, by application of the oxidant menadione, release of Ca(2+) from stores leads to oscillatory global waves, associated with partial mitochondrial depolarisation and transient MPTP opening; apoptotic cell death is promoted via the intrinsic pathway, when associated with generation of reactive oxygen species. Apoptosis, induced by menadione or bile acids, is potentiated by inhibition of an endogenous detoxifying enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), suggesting its importance as a defence mechanism that may influence cell fate.

Probability of metastable configurations in spherical three-dimensional Yukawa crystals.

Recently the occurrence probabilities of ground and metastable states of three-dimensional Yukawa clusters with 27 and 31 particles have been analyzed in dusty plasma experiments [D. Block, Phys. Plasmas 15, 040701 (2008)]. There it was found that, in many cases, the ground state appeared substantially less frequently than excited states. Here we analyze this question theoretically by means of molecular dynamics (MD) and Monte Carlo simulations and an analytical method based on the canonical partition function. We confirm that metastable states can occur with a significantly higher probability than the ground state. The results strongly depend on the screening parameter of the Yukawa interaction and the damping coefficient used in the MD simulations. The analytical method allows one to gain insight into the mechanisms being responsible for the occurrence probabilities of metastable states in strongly correlated finite systems.

Role of shear rate and platelets in promoting fibrin formation on rabbit subendothelium. Studies utilizing patients with quantitative and qualitative platelet defects.

The deposition of platelets on subendothelium of rabbit aortic segments exposed to non-anticoagulated human blood increased progressively with increasing wall shear rates (50-2,600 s-1), whereas fibrin deposition decreased. Studies in normal subjects and patients with platelet disorders suggested that, under the conditions used, platelets were essential for fibrin deposition at intermediate (650 s-1) but not low (50 s-1) shear rates. Fibrin deposition was markedly diminished in a patient with Scott syndrome whose platelets have a diminished capacity to bind Factor Xa and activate Factors IX and II. In glycoprotein IIb-IIIa deficiency, fibrin deposition was normal (or somewhat increased), whereas in glycoprotein Ib deficiency the association of fibrin with platelets, but not subendothelium, was decreased. The findings indicate that platelets, perhaps through surface localization of coagulation proteins, promote fibrin deposition on subendothelium at arterial shear rates and suggest that agents directed against platelet coagulant properties could be antithrombotic.

Platelet interaction with rabbit subendothelium in von Willebrand's disease: altered thrombus formation distinct from defective platelet adhesion.

Blood interaction with the subendothelium of rabbit aorta was investigated in an annular perfusion chamber using patients with von Willebrand's disease, hemophilia, and afibrinogenemia. The vessels were exposed to nonanticoagulated blood for a range of flow conditions (wall shear rates of 650-3,300 s-1) and exposure times (1.5-10 min). The resultant platelet and fibrin interaction was quantified by the use of several morphometric techniques, one of which was developed to measure more precisely the dimensions (height and volume) of platelet thrombi attached to the subendothelium. A major finding was that under flow conditions in which little or no defect in platelet adhesion was observed in von Willebrand's disease, platelet thrombus height and volume in this disorder were significantly reduced as compared with normal controls or patients with hemophilia. Thus, Factor VIII/von Willebrand factor (VIII/VWF) may mediate not only the adhesion of platelets to subendothelium but also platelet-platelet attachments necessary for normal thrombus development. The level of Factor VIII:coagulant activity (VIII: C) was also observed to influence the resultant thrombus height and volume deposited on subendothelium, presumably through the generation of thrombin or some other procoagulant factor preceding fibrin formation, since normal values of thrombus dimensions were always observed in a patient with a fibrinogen deficiency. The influence of VIII:C became greater as shear rate was reduced, whereas as shear rate was increased, VIII/VWF was more dominant in determining the resultant platelet deposition on subendothelium. Thus, the deficiencies of VIII:C and VIII/VWF in hemophilia and von Willebrand's disease can lead to various abnormalities in platelet and fibrin association with subendothelium. The importance of a particular deficiency will depend strongly on the local blood flow conditions.

Endothelial cells stimulated with tumor necrosis factor-alpha express varying amounts of tissue factor resulting in inhomogenous fibrin deposition in a native blood flow system. Effects of thrombin inhibitors.

TNF-alpha induces changes in endothelial cell functions, such as upregulation of tissue factor, resulting in endothelial procoagulant activity which may play a role in disseminated intravascular coagulation. The procoagulant activity of TNF-alpha-stimulated endothelial cell monolayers was studied in a human ex vivo native (nonanticoagulated) blood flow system using the three thrombin inhibitors recombinant hirudin, Ro 46-6240, and heparin. Under venous blood flow conditions (shear rate 65 s-1) recombinant hirudin, Ro 46-6240, and heparin inhibited fibrin deposition on the endothelial cells by 50% at concentrations of 14, 28, and 412 ng/ml, respectively. The highest tested concentrations of the thrombin inhibitors reduced the postchamber fibrinopeptide A levels from 713 +/- 69 to < 70 ng/ml. Surprisingly, even at relatively high inhibitor concentrations, some local fibrin deposits were found on TNF-alpha-stimulated cells, suggesting that some endothelial cells possess higher procoagulant activity than others. Therefore, the surface expression pattern of tissue factor, the primary initiator of coagulation in this system, was examined by immunogold-silver staining. The results showed that the tissue factor density on the cell surface varied strongly among TNF-alpha-stimulated endothelial cells. Using TNF receptor-selective agonistic mutants of TNF-alpha, it was demonstrated further that the heterogenous surface expression of tissue factor was mediated entirely by the 55-kD TNF receptor and did not involve the 75-kD TNF receptor. We conclude that in this system TNF-alpha induces heterogenous tissue factor expression which may lead to a high local thrombin concentration, such that even in the presence of thrombin inhibitors focal fibrin deposition occurs.

Ground state of a confined Yukawa plasma.

The ground state of an externally confined one-component Yukawa plasma is derived analytically. In particular, the radial density profile is computed. The results agree very well with computer simulations of three-dimensional spherical Coulomb crystals. We conclude in presenting an exact equation for the density distribution for a confinement potential of arbitrary geometry.

Mechanisms underlying aortic dilatation in congenital aortic valve malformation.

BACKGROUND: The high incidence of aortic disease in subjects with congenital aortic valve malformations suggests a causative relationship between these 2 conditions. The histological observation in aortic dilatation/aneurysm/dissection is Erdheim cystic medial necrosis (CMN), a noninflammatory loss of smooth muscle cells (SMCs), fragmentation of elastic fibers, and mucoid degeneration. METHODS AND RESULTS: To examine whether apoptosis is 1 of the mechanisms underlying CMN and aortic medial layer SMC loss, ascending aortic wall specimens from 32 patients were collected at cardiothoracic surgery and examined by histochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. From echocardiography results, 4 groups of patients were identified: bicuspid valve carriers with (bi/dil) or without (bi/0) aortic dilatation and tricuspid valve carriers with (tri/dil) or without (tri/0) aortic dilatation. Massive focal apoptosis was observed in the medial layers of bi/dil (mean apoptotic index [mAI], 8.1+/-6.0) and tri/dil (mAI, 8.1+/-8.3) compared with tri/0 (mAI, 0.9+/-1.2; P=0.0079 and P=0.037). In bi/0 (mAI, 9.1+/-5.7) compared with tri/0 (mAI, 0.9+/-1.2), rates of medial SMC apoptosis were increased (P=0.0025). Bi/dil (mean age, 40. 6+/-15.7 years) were significantly younger than tri/dil (mean age, 56.4+/-12.8 years) undergoing the same operation (P=0.0123). CONCLUSIONS: Premature medial layer SMC apoptosis could be part of a genetic program underlying aortic disease in patients with aortic valve malformations.

Effect of stenosis geometry on the Doppler-catheter gradient relation in vitro: a manifestation of pressure recovery.

OBJECTIVES: This study investigated the effect of stenosis geometry on the Doppler-catheter gradient relation. BACKGROUND: Although gradient estimation by Doppler ultrasound has been shown to be accurate in various clinical and in vitro settings, there have also been reports of substantial discrepancies between Doppler and catheter gradients. These conflicting results may be due to differences in geometry and hemodynamic characteristics of flow obstructions. METHODS: Stenoses of various geometry were simultaneously studied with continuous wave Doppler and catheter technique in a well controlled pulsatile flow model. RESULTS: Doppler and catheter gradients correlated very well regardless of stenosis geometry and site of distal catheter measurement (r = 0.98 to 0.99, SEE = 1.8 to 5.3 mm Hg). When the catheter was pulled back through the stenosis, the highest gradients were found in or close to the stenosis. When these catheter gradients were compared with Doppler gradients, the agreement between the two techniques was excellent regardless of stenosis geometry (slope 0.97; mean difference 0.6 +/- 2.0 mm Hg). However, when distal pressures were measured 10 cm downstream from the stenotic segment, the slope of the regression line, and therefore the agreement between Doppler and catheter gradients, differed for the different stenosis types (slopes from 0.98 to 1.69). In stenoses with abrupt narrowing and abrupt expansion, agreement was acceptable. Doppler gradients were only slightly greater than catheter gradients (mean difference 4.5 +/- 5.2 mm Hg). In stenoses with a gradually tapering inlet and outlet, the Doppler-catheter gradient relation was dependent on the outflow angle. Good agreement was found for an angle of 60 degrees (mean difference 0.6 +/- 1.8 mm Hg). In stenoses with a 40 degrees outflow angle, Doppler gradients exceeded the catheter gradients by 13% on average; for stenoses with a 20 degrees outflow angle, Doppler gradients exceeded catheter gradients by 46 +/- 11.4%, with differences as great as 65 mm Hg. These results were identical for stenoses gradually tapering outward to the distal tubing diameter and those with abrupt expansion after 2 cm of gradual expansion. The results were also not affected by changing the inflow angle from 20 degrees to 60 degrees. However, an abrupt narrowing instead of a tapering inlet significantly altered the Doppler-catheter gradient relation (p < 0.001); Doppler gradients exceeded the catheter gradients by 34 +/- 10% for this stenosis type. CONCLUSIONS: Doppler gradients accurately reflect the highest gradients across flow obstructions that occur in the vena contracta. However, these gradients may be significantly greater than catheter gradients that are measured farther downstream, as is usually the case in clinical catheterization studies. These discrepancies are due to pressure recovery. The magnitude of pressure recovery is highly dependent on the stenosis geometry, which therefore significantly affects the Doppler-catheter gradient relation. It is the outflow geometry that predominantly influences this relation, but the shape of the inlet may affect the results as well. Although pressure recovery occurs even in stenoses with abrupt narrowing and abrupt expansion, the phenomenon is most likely to become clinically relevant in stenoses with a gradually tapering inlet and outlet with an outflow angle < or = 20 degrees.

Effect of prosthetic aortic valve design on the Doppler-catheter gradient correlation: an in vitro study of normal St. Jude, Medtronic-Hall, Starr-Edwards and Hancock valves.

To evaluate the normal range of Doppler-derived velocities and gradients, their relation to direct flow measurements and the importance of prosthetic valve design on the relation between Doppler and catheter-derived gradients, five sizes of normal St. Jude bileaflet, Medtronic-Hall tilting disc, Starr-Edwards caged ball and Hancock bioprosthetic aortic valves were studied with use of a pulsatile flow model. A strong linear correlation between peak velocity and peak flow, and mean velocity and mean flow, was found in all four valve types (r = 0.96 to 0.99). In small St. Jude and Hancock valves, Doppler velocities and corresponding gradients increased dramatically with increasing flow, resulting in velocities and gradients as high as 4.7 m/s and 89 mm Hg, respectively. The ratio of velocity across the valve to velocity in front of the valve (velocity ratio) was independent of flow in all St. Jude, Medtronic-Hall, Starr-Edwards and Hancock valves when the two lowest flow rates were excluded for Hancock valves. Although Doppler peak and mean gradients correlated well with catheter peak and mean gradients in all four valve types, the actual agreement between the two techniques was acceptable only in Hancock and Medtronic-Hall valves. For St. Jude and Starr-Edwards valves, Doppler gradients significantly and consistently exceeded catheter gradients with differences as great as 44 mm Hg. Thus, Doppler velocities and gradients across normal prosthetic heart valves are highly flow dependent. However, the velocity ratio is independent of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved assessment of mitral valve stenosis by volumetric real-time three-dimensional echocardiography.

OBJECTIVES: This study was performed to determine the feasibility, accuracy and reproducibility of real-time volumetric three-dimensional echocardiography (3-D echo) for the estimation of mitral valve area in patients with mitral valve stenosis. BACKGROUND: Planimetry of the mitral valve area (MVA) by two-dimensional echocardiography (2-D echo) requires a favorable parasternal acoustic window and depends on operator skill. Transthoracic volumetric 3-D echo allows reconstruction of multiple 2-D planes in any desired orientation and is not limited to parasternal acquisition, and could thus enhance the accuracy and feasibility of calculating MVA. METHODS: In 48 patients with mitral stenosis (40 women; mean age 61 +/- 13 years) MVA was determined by planimetry using volumetric 3-D echo and compared with measurements obtained by 2-D echo and Doppler pressure half-time (PHT). All measurements were performed by two independent observers. Volumetric data were acquired from an apical view. RESULTS: Although 2-D echo allowed planimetry of the mitral valve in 43 of 48 patients (89%), calculation of the MVA was possible in all patients when 3-D echo was used. Mitral valve area by 3-D echo correlated well with MVA by 2-D echo (r = 0.93, mean difference, 0.09 +/- 0.14 cm2) and by PHT (r = 0.87, mean difference, 0.16 +/- 0.19 cm2). Interobserver variability was significantly less for 3-D echo than for 2-D echo (SD 0.08cm2 versus SD 0.23cm2, p < 0.001). Furthermore, it was much easier and faster to define the image plane with the smallest orifice area when 3-D echo was used. CONCLUSIONS: Transthoracic real-time volumetric 3-D echo provides accurate and highly reproducible measurements of mitral valve area and can easily be performed from an apical approach.

"Overestimation" of catheter gradients by Doppler ultrasound in patients with aortic stenosis: a predictable manifestation of pressure recovery.

OBJECTIVES: This study sought to evaluate whether pressure recovery can cause significant differences between Doppler and catheter gradients in patients with aortic stenosis, and whether these differences can be predicted by Doppler echocardiography. BACKGROUND: Pressure recovery has been shown to be a source of discrepancy between Doppler and catheter gradients across aortic stenoses in vitro. However, the clinical relevance of this phenomenon for the Doppler assessment of aortic stenosis has not been evaluated in patients. METHODS: Twenty-three patients with various degrees of aortic stenosis were studied with Doppler echocardiography and catheter technique within 24 h. Using an equation previously validated in vitro, pressure recovery was estimated from peak transvalvular velocity, aortic valve area and cross-sectional area of the ascending aorta and compared with the observed differences between Doppler and catheter gradients. Doppler gradients were also corrected by subtracting the predicted pressure recovery and then were compared with the observed catheter gradients. RESULTS: Predicted differences between Doppler and catheter gradients due to pressure recovery ranged from 5 to 82 mm Hg (mean +/- SD, 19 +/- 16 mm Hg) and 3 to 54 mm Hg (12 +/- 11 mm Hg) for peak and mean gradients, respectively. They compared well with the observed Doppler-catheter gradient differences, ranging from -5 to 75 mm Hg (18 +/- 18 mm Hg) and -7 to 48 mm Hg (11 +/- 13 mm Hg). Good correlation between predicted pressure recovery and observed gradient differences was found (r = 0.90 and 0.85, respectively). Both the noncorrected and the corrected Doppler gradients correlated well with the catheter gradients (r = 0.93-0.97). However, noncorrected Doppler gradients significantly overestimated the catheter gradients (slopes, 1.36 and 1.25 for peak and mean gradients, respectively), while Doppler gradients corrected for pressure recovery showed good agreement with catheter gradients (slopes, 1.03 and 0.96; standard error of estimate [SEE] 8.1 and 6.9 mm Hg; mean difference +/- SD 0.4 +/- 8.0 mm Hg and 1.1 +/- 6.8 mm Hg for peak and mean gradients, respectively). CONCLUSIONS: Significant pressure recovery can occur in patients with aortic stenosis and can cause discrepancies between Doppler and catheter gradients. However, pressure recovery and the resulting differences between Doppler and catheter measurements may be predicted from Doppler velocity, aortic valve area and size of the ascending aorta.

Suppression of the vascular response to injury: the role of angiotensin-converting enzyme inhibitors.

Smooth muscle cell proliferation and formation of extracellular matrix are parts of the repair process after vascular injury. Similar processes occur after coronary angioplasty and, in approximately 33% of vessels, lead to intimal hyperplasia and vascular restenosis within 6 months after angioplasty. In a rat model of balloon catheterization, the proliferative response to balloon injury was reduced by 70% and the area of vascular wall covered by lesion formation was decreased by 45% in rats treated with the angiotensin-converting enzyme inhibitor cilazapril. Other antihypertensive agents were much less active when tested for suppression of intimal hyperplasia after balloon injury: verapamil 0%, minoxidil 4% and hydralazine 34%. For cilazapril at the dose of 10 mg/kg per day, approximately 20% greater suppression of intimal hyperplasia was seen when the treatment was started 6 days before balloon injury. Treatment of rats from the time of balloon catheterization with both cilazapril (10 mg/kg per day) and heparin infusion (0.3 mg/kg per h) resulted in essentially complete (greater than 90%) inhibition of intimal hyperplasia. These data indicate that the angiotensin-converting enzyme inhibitor cilazapril specifically inhibits the proliferative response to balloon injury and that heparin and cilazapril inhibit intimal hyperplasia through different mechanisms. The data also suggest that the use of pharmacologic combinations may have therapeutic usefulness to prevent late restenosis after coronary angioplasty.

Estimation of coronary flow reserve by transesophageal coronary sinus Doppler measurements in patients with syndrome X and patients with significant left coronary artery disease.

OBJECTIVES: This study sought to determine the feasibility of coronary sinus flow velocity analysis by transesophageal Doppler echocardiography for estimation of coronary flow reserve in patients with syndrome X and patients with coronary artery disease. BACKGROUND: Coronary flow reserve provides useful information in patients with coronary artery disease and patients with syndrome X. Current methods of measuring coronary flow reserve are invasive or require extensive laboratory equipment, or both. Transesophageal Doppler recordings of coronary sinus flow velocity before and after vasodilator application may allow noninvasive determination of coronary flow reserve. METHODS: We obtained coronary sinus flow velocity recordings before and after dipyridamole administration (0.6 mg/kg body weight per 5 min) in 9 patients with syndrome X, 14 with significant left coronary artery disease and 22 age-matched control patients. We used the formula anterograde minus retrograde flow velocity time integral times heart rate as an index of coronary sinus flow. Coronary flow reserve was calculated by dividing coronary sinus flow variables after dipyridamole administration by the respective baseline values. RESULTS: Technically adequate recordings were obtained in 44 (98%) of 45 patients. Compared with that in the control group (2.78 +/- 0.95 [mean +/- SD]), coronary flow reserve was significantly lower in patients with syndrome X (1.21 +/- 0.23, p < or = 0.001) as well as in those with coronary artery disease (1.47 +/- 0.7, p < or = 0.001). Using a cutoff coronary flow reserve value of 1.8, sensitivity, specificity and overall predictive value of coronary flow reserve determinations were, respectively, 100%, 91% and 94% for syndrome X and 86%, 91% and 89% for coronary artery disease. CONCLUSIONS: Coronary flow reserve calculation by transesophageal coronary sinus flow velocity recordings is feasible in a large proportion of patients and might be useful for the noninvasive evaluation of patients with syndrome X and patients with severe left coronary artery disease.

Stereolithographic biomodeling to create tangible hard copies of cardiac structures from echocardiographic data: in vitro and in vivo validation.

OBJECTIVES: This study investigated the feasibility, accuracy and clinical potential of creating polymer hard copies of echocardiographic data using stereolithography. BACKGROUND: Three-dimensional (3D) echocardiography has so far been limited by the need to display reconstructed 3D objects on a two-dimensional screen. Thus, tangible stereolithographic polymer models created from echocardiographic data could enhance our spatial perception of cardiac anatomy and pathology. METHODS: Hard-copy replicas of water-filled latex balloon phantoms (n = 7) and porcine liver specimens (n = 12) were generated from echocardiographic images using stereolithography (computerized laser polymerization). In addition, we created 24 models of the mitral valve from 12 transesophageal studies (normal = 6, mitral stenosis n = 4, prolapse/flail leaflet n = 8, annular dilation n = 2, leaflet restriction n = 2 and following mitral valve repair n = 2). RESULTS: Excellent agreement was found for comparison of volumes (r = 0.98, SEE = 3.46 mm3, mean difference = 0.25 +/- 3.33 mm3) and maximal dimensions (r = 0.99, SEE = 0.16 cm, mean difference = 0.03 +/- 0.16 cm) between phantoms and their corresponding replicas. Visual and tactile examination of mitral valve models by two blinded observers allowed correct depiction of mitral valve anatomy and pathology in all cases. CONCLUSIONS: Stereolithographic modeling of echocardiographic images is feasible and provides tangible polyacrylic models that are true to scale, shape and volume. Such models offer accurate depiction of mitral valve anatomy and pathology in patients studied with transesophageal echocardiography. This technique could have substantial impact on diagnosis, management and preoperative planning in complex cardiovascular disorders.

Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts.

OBJECTIVES: We examined the relationship among viability assessment by dobutamine echocardiography (DE), positron emission tomography (PET) and thallium-201 single-photon emission computed tomography (TI-SPECT) to the degree of fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to be sensitive in identifying viability of asynergic myocardium. However, PET and TI-SPECT indicated viability in a significant percentage of segments without dobutamine response or functional improvement after revascularization. METHODS: Twelve patients with coronary artery disease and severely reduced left ventricular function (EF 14.5+/-5.2%) were studied with DE prior to cardiac transplantation: 5 had additional PET and 7 had TI-SPECT studies. Results of the three techniques were compared to histologic findings of the explanted hearts. RESULTS: Segments with >75% viable myocytes by histology were determined to be viable in 78%, 89% and 87% by DE, PET and TI-SPECT; those with 50-75% viable myocytes in 71%, 50% and 87%, respectively. Segments with 25-50% viable myocytes showed response to dobutamine in only 15%, but were viable in 60% by PET and 82% by TI-SPECT. Segments with <25% viable myocytes responded to dobutamine in 19%; however, PET and TI-SPECT demonstrated viability in 33% and 38%, respectively. Discrepant segments without dobutamine response but viability by PET and SPECT had significantly more viable myocytes by pathology than did those classified in agreement to be nonviable but had significantly less viable myocytes than those classified in agreement to be viable (p < .001). CONCLUSIONS: These findings suggest that contractile reserve as evidenced by a positive dobutamine response requires at least 50% viable myocytes in a given segment whereas scintigraphic methods also identify segments with less viable myocytes. Thus, the methods may provide complementary information: Nuclear techniques appear to be highly sensitive for the detection of myocardial viability, and negative tests make it highly unlikely that a significant number of viable myocytes are present in a given segment. Conversely, dobutamine echo may be particularly useful for predicting recovery of systolic function after revascularization.