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1.
Circulation ; 104(16): 1952-7, 2001 Oct 16.
Article in English | MEDLINE | ID: mdl-11602500

ABSTRACT

BACKGROUND: Ischemic mitral regurgitation (MR) was first ascribed to papillary muscle (PM) contractile dysfunction. Current theories include apical leaflet tethering caused by left ventricular (LV) distortion, but PM dysfunction is still postulated and commonly diagnosed. PM contraction, however, parallels apical tethering, suggesting the hypothesis that PM contractile dysfunction can actually diminish MR due to ischemic distortion of the inferior base alone. METHODS AND RESULTS: We therefore occluded the proximal circumflex circulation in 7 sheep while maintaining PM perfusion, confirmed by contrast echocardiography. By 3D echocardiography, we measured the tethering distance between the ischemic medial PM tip and anterior annulus and LV ejection volume to give MR (by subtracting flowmeter LV outflow). In 6 sheep without initial MR, inferior ischemia alone produced PM tip retraction with restricted leaflet closure and mild-to-moderate MR (regurgitant fraction, 25.2+/-2.8%). Adding PM ischemia consistently decreased MR and tethering distance (5.2+/-0.3 to 1.4+/-0.3 mL; +3.8+/-0.5 mm to -2.2+/-0.7 mm axially relative to baseline; P<0.001) as PM strain rate decreased from +0.78+/-0.07 per second (contraction) to -0.42+/-0.06 per second (elongation, P<0.001) and leaflet tenting decreased. In one sheep, prolapse and MR resolved with inferior ischemia and recurred with PM ischemia. CONCLUSIONS: PM contractile dysfunction can paradoxically decrease MR from inferobasal ischemia by reducing leaflet tethering to improve coaptation. This emphasizes the role of geometric factors in ischemic MR mechanism and potential therapy.


Subject(s)
Echocardiography/methods , Mitral Valve Insufficiency/physiopathology , Myocardial Contraction , Myocardial Ischemia/physiopathology , Papillary Muscles/physiopathology , Animals , Disease Models, Animal , Echocardiography, Doppler , Echocardiography, Three-Dimensional , Heart Conduction System/physiopathology , Hemodynamics , Internet , Mitral Valve Insufficiency/complications , Myocardial Contraction/physiology , Myocardial Ischemia/complications , Sheep , Stress, Mechanical
2.
Circulation ; 104(16): 1958-63, 2001 Oct 16.
Article in English | MEDLINE | ID: mdl-11602501

ABSTRACT

BACKGROUND: Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Because such MR is related to increased leaflet tethering by displaced attachments to the papillary muscles (PMs), it is incompletely treated by annular reduction. We therefore addressed the hypothesis that such MR can be reduced by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. This was tested in 8 mitral valves: a porcine in vitro pilot with PM displacement and 7 sheep with acute inferobasal infarcts studied in vivo with three-dimensional (3D) echo to quantify MR in relation to 3D valve geometry. METHODS AND RESULTS: In all 8 valves, PM displacement restricted leaflet closure, with anterior leaflet angulation at the basal chord insertion, and mild-to-moderate MR. Cutting the 2 central basal chordae reversed this without prolapse. In vivo, MR increased from 0.8+/-0.2 to 7.1+/-0.5 mL/beat after infarction and then decreased to 0.9+/-0.1 mL/beat with chordal cutting (P<0.0001); this paralleled changes in the 3D leaflet area required to cover the orifice as dictated by chordal tethering (r(2)=0.76). CONCLUSIONS: Cutting a minimum number of basal chordae can improve coaptation and reduce ischemic MR. Such an approach also suggests the potential for future minimally invasive implementation.


Subject(s)
Cardiac Surgical Procedures/methods , Chordae Tendineae/surgery , Mitral Valve Insufficiency/surgery , Myocardial Ischemia/surgery , Animals , Disease Models, Animal , Hemodynamics , In Vitro Techniques , Mitral Valve/physiopathology , Mitral Valve/surgery , Mitral Valve Insufficiency/complications , Mitral Valve Insufficiency/physiopathology , Myocardial Ischemia/complications , Myocardial Ischemia/physiopathology , Pilot Projects , Sheep , Stroke Volume , Swine , Treatment Outcome , Ventricular Function, Left
3.
J Am Coll Cardiol ; 37(2): 641-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11216991

ABSTRACT

OBJECTIVES: This study aimed to separate proposed mechanisms for segmental ischemic mitral regurgitation (MR), including left ventricular (LV) dysfunction versus geometric distortion by LV dilation, using models of acute and chronic segmental ischemic LV dysfunction evaluated by three-dimensional (3D) echocardiography. BACKGROUND: Dysfunction and dilation-both mechanisms with practical therapeutic implications-are difficult to separate in patients. METHODS: In seven dogs with acute left circumflex (LCX) coronary ligation, LV expansion was initially restricted and then permitted to occur. In seven sheep with LCX branch ligation, LV expansion was also initially limited but became prominent with remodeling over eight weeks. Three-dimensional echo reconstruction quantified mitral apparatus geometry and MR volume. RESULTS: In the acute model, despite LV dysfunction with ejection fraction = 23 +/- 8%, MR was initially trace with limited LV dilation, but it became moderate with subsequent prominent dilation. In the chronic model, MR was also initially trace, but it became moderate over eight weeks as the LV dilated and changed shape. In both models, the only independent predictor of MR volume was increased tethering distance from the papillary muscles (PMs) to the anterior annulus, especially medial and posterior shift of the ischemic medial PM, measured by 3D reconstruction (r2 = 0.75 and 0.86, respectively). Mitral regurgitation volume did not correlate with LV ejection fraction or dP/dt. CONCLUSIONS: Segmental ischemic LV contractile dysfunction without dilation, even in the PM territory, fails to produce important MR. The development of MR relates strongly to changes in the 3D geometry of the mitral apparatus, with implications for approaches to restore a more favorable configuration.


Subject(s)
Coronary Disease/diagnostic imaging , Echocardiography, Three-Dimensional , Mitral Valve Insufficiency/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , Animals , Cardiac Volume/physiology , Dogs , Female , Male , Papillary Muscles/diagnostic imaging , Sheep , Stroke Volume/physiology
4.
Circulation ; 102(9): 1053-61, 2000 Aug 29.
Article in English | MEDLINE | ID: mdl-10961972

ABSTRACT

BACKGROUND: Noninvasive quantification of regurgitation is limited because Doppler measures velocity, not flow. Because backscattered Doppler power is proportional to sonified blood volume, power times velocity should be proportional to flow rate. Early studies, however, suggested that this held only for laminar flow, not for regurgitant jets, in which turbulence and fluid entrainment augment scatter. We therefore hypothesized that this Doppler power principle can be applied at the proximal vena contracta, where flow is laminar before entrainment, so that the power-times-velocity integral should vary linearly with flow rate and its time integral with stroke volume (SV). METHODS AND RESULTS: This was tested in vitro with steady and pulsatile flow through 0.07- to 0.8-cm(2) orifices and in 36 hemodynamic stages in vivo, replacing the left atrium with a rigid chamber and column for direct visual recording of mitral regurgitant SV (MRSV). In 12 patients, MRSV was compared with MRI mitral inflow minus aortic outflow and in 11 patients with 3D echo left ventricular ejection volume-Doppler aortic forward SV. Vena contracta power in the narrow high-velocity spectrum from a broad measuring beam was calibrated against that from a narrow reference beam of known area. Calculated and actual flow rates and SV correlated well in vitro (r=0.99, 0.99; error=-1.6+/-2.5 mL/s, -2. 4+/-2.9 mL), in vivo (MRSV: r=0.98, error=0.04+/-0.87 mL), and in patients (MRSV: r=0.98, error=-2.8+/-4.5 mL). CONCLUSIONS: The power-velocity integral at the vena contracta provides an accurate direct measurement of regurgitant flow, overcoming the limitations of existing Doppler techniques.


Subject(s)
Echocardiography, Doppler , Mitral Valve Insufficiency/diagnosis , Stroke Volume , Animals , Blood Flow Velocity , Dogs , Echocardiography, Three-Dimensional , Female , Hemorheology , Humans , In Vitro Techniques , Magnetic Resonance Imaging , Male , Middle Aged , Mitral Valve Insufficiency/diagnostic imaging , Models, Biological , Transducers , Veins/diagnostic imaging
5.
Circulation ; 101(23): 2756-63, 2000 Jun 13.
Article in English | MEDLINE | ID: mdl-10851215

ABSTRACT

BACKGROUND: Mechanistic insights from 3D echocardiography (echo) can guide therapy. In particular, ischemic mitral regurgitation (MR) is difficult to repair, often persisting despite annular reduction. We hypothesized that (1) in a chronic infarct model of progressive MR, regurgitation parallels 3D changes in the geometry of mitral leaflet attachments, causing increased leaflet tethering and restricting closure; therefore, (2) MR can be reduced by restoring tethering geometry toward normal, using a new ventricular remodeling approach based on 3D echo findings. METHODS AND RESULTS: We studied 10 sheep by 3D echo just after circumflex marginal ligation and 8 weeks later. MR, at first absent, became moderate as the left ventricle (LV) dilated and the papillary muscles shifted posteriorly and mediolaterally, increasing the leaflet tethering distance from papillary muscle tips to the anterior mitral annulus (P<0.0001). To counteract these shifts, the LV was remodeled by plication of the infarct region to reduce myocardial bulging, without muscle excision or cardiopulmonary bypass. Immediately and up to 2 months after plication, MR was reduced to trace-to-mild as tethering distance was decreased (P<0.0001). LV ejection fraction, global LV end-systolic volume, and mitral annular area were relatively unchanged. By multiple regression, the only independent predictor of MR was tethering distance (r(2)=0.81). CONCLUSIONS: Ischemic MR in this model relates strongly to changes in 3D mitral leaflet attachment geometry. These insights from quantitative 3D echo allowed us to design an effective LV remodeling approach to reduce MR by relieving tethering.


Subject(s)
Cardiac Surgical Procedures/methods , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/surgery , Ventricular Remodeling , Acute Disease , Animals , Chronic Disease , Disease Models, Animal , Echocardiography, Three-Dimensional , Mitral Valve Insufficiency/complications , Myocardial Ischemia/etiology , Sheep
6.
J Am Coll Cardiol ; 33(2): 538-45, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9973036

ABSTRACT

OBJECTIVES: We used the Doppler proximal flow convergence technique as a physiologic tool to explore the effects of the time courses of mitral annular area and transmitral pressure on dynamic changes in regurgitant orifice area. BACKGROUND: In functional mitral regurgitation (MR), regurgitant flow rate and orifice area display a unique pattern, with peaks in early and late systole and a midsystolic decrease. Phasic changes in both mitral annular area and the transmitral pressure acting to close the leaflets, which equals left ventricular-left atrial pressure, have been proposed to explain this dynamic pattern. METHODS: In 30 patients with functional MR, regurgitant orifice area was obtained as flow (from M-mode proximal flow convergence traces) divided by orifice velocity (v) from the continuous wave Doppler trace of MR, transmitral pressure as 4v(2), and mitral annular area from two apical diameters. RESULTS: All patients had midsystolic decreases in regurgitant orifice area that mirrored increases in transmitral pressure, while mitral annular area changed more gradually. By stepwise multiple regression analysis, both mitral annular area and transmitral pressure significantly affected regurgitant orifice area; however, transmitral pressure made a stronger contribution (r2 = 0.441) than mitral annular area (added r2 = 0.008). Similarly, the rate of change of regurgitant orifice area more strongly related to that of transmitral pressure (r2 = 0.638) than to that of mitral annular area (added r2 = 0.003). A similar regurgitant orifice area time course was observed in four patients with fixed mitral annuli due to Carpentier ring insertion. CONCLUSIONS: In summary, the time course and rate of change of regurgitant orifice area in patients with functional MR are predominantly determined by dynamic changes in the transmitral pressure acting to close the valve. Thus, although mitral annular area helps determine the potential for MR, transmitral pressure appears important in driving the leaflets toward closure, and would be of value to consider in interventions aimed at reducing the severity of MR.


Subject(s)
Echocardiography, Doppler, Color , Mitral Valve Insufficiency/physiopathology , Mitral Valve/physiopathology , Aged , Blood Flow Velocity , Cardiomyopathy, Dilated/complications , Cardiomyopathy, Dilated/diagnostic imaging , Cardiomyopathy, Dilated/physiopathology , Female , Humans , Image Processing, Computer-Assisted , Male , Mitral Valve/diagnostic imaging , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/etiology , Observer Variation , Severity of Illness Index , Stroke Volume , Systole , Ventricular Pressure
7.
Cardiologia ; 43(10): 1011-6, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9922564

ABSTRACT

Functional MR is an important complication, which adversely affects the prognosis of patients with ischemic heart disease or global LV dysfunction. Two-dimensional Doppler echocardiography is a noninvasive and useful method for the diagnosis of functional MR. However, the pathophysiology of functional MR is not yet established, therefore, extensive investigations are necessary to understand its basic mechanism and establish effective and practical method for the prevention and treatment of functional MR.


Subject(s)
Mitral Valve Insufficiency/physiopathology , Animals , Humans , Incidence , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/epidemiology , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/therapy , Terminology as Topic
8.
Circulation ; 96(6): 1999-2008, 1997 Sep 16.
Article in English | MEDLINE | ID: mdl-9323092

ABSTRACT

BACKGROUND: Recent advances in three-dimensional (3D) echocardiography allow us to address uniquely 3D scientific questions, such as the mechanism of functional mitral regurgitation (MR) in patients with left ventricular (LV) dysfunction and its relation to the 3D geometry of mitral leaflet attachments. Competing hypotheses include global LV dysfunction with inadequate leaflet closing force versus geometric distortion of the mitral apparatus by LV dilatation, which increases leaflet tethering and restricts closure. Because geometric changes generally accompany dysfunction, these possibilities have been difficult to separate. METHODS AND RESULTS: We created a model of global LV dysfunction by esmolol and phenylephrine infusion in six dogs. initially with LV expansion limited by increasing pericardial restraint and then with the pericardium opened. The mid-systolic 3D relations of the papillary muscle (PM) tips and mitral valve were reconstructed. Despite severe LV dysfunction (ejection fraction, 18+/-6%), only trace MR developed when pericardial restraint limited LV dilatation; with the pericardium opened, moderate MR accompanied LV dilatation (end-systolic volume, 44+/-5 mL versus 12+/-5 mL control, P<.001). Mitral regurgitant volume and orifice area did not correlate with LV ejection fraction and dP/dt (global function) but did correlate with changes in the tethering distance from the PMs to the anterior annulus derived from the 3D reconstructions, especially PM shifts in the posterior and mediolateral directions, as well as with annular area (P<.0005). By multiple regression, only changes in the PM-to-annulus distance independently predicted MR volume and orifice area (R2=.82 to .85, P=2x10(-7) to 6x10(-8)). CONCLUSIONS: LV dysfunction without dilatation fails to produce important MR. Functional MR relates strongly to changes in the 3D geometry of the mitral valve attachments at the PM and annular levels, with practical implications for approaches that would restore a more favorable configuration.


Subject(s)
Echocardiography, Three-Dimensional , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve/pathology , Papillary Muscles/pathology , Animals , Coronary Circulation/physiology , Disease Models, Animal , Dogs , Echocardiography, Three-Dimensional/standards , Mitral Valve/physiopathology , Mitral Valve Insufficiency/complications , Mitral Valve Insufficiency/physiopathology , Papillary Muscles/physiopathology , Reproducibility of Results , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology
9.
Circulation ; 94(3): 452-9, 1996 Aug 01.
Article in English | MEDLINE | ID: mdl-8759088

ABSTRACT

BACKGROUND: Three-dimensional echocardiography can allow us to address uniquely three-dimensional scientific questions, for example, the hypothesis that the impact of a stenotic valve depends not only on its limiting orifice area but also on its three-dimensional geometry proximal to the orifice. This can affect the coefficient of orifice contraction (Cc = effective/anatomic area), which is important because for a given flow rate and anatomic area, a lower Cc gives a higher velocity and pressure gradient, and Cc, routinely assumed constant in the Gorlin equation, may vary with valve shape (60% for a flat plate, 100% for a tube). To date, it has not been possible to study this with actual valve shapes in patients. METHODS AND RESULTS: Three-dimensional echocardiography reconstructed valve geometries typical of the spectrum in patients with mitral stenosis: mobile doming, intermediate conical, and relatively flat immobile valves. Each geometry was constructed with orifice areas of 0.5, 1.0 and 1.5 cm2 by stereolithography (computerized laser polymerization) (total, nine valves) and studied at physiological flow rates. Cc varied prominently with shape and was larger for the longer, tapered dome (more gradual flow convergence proximal and distal to the limiting orifice): for an anatomic orifice of 1.5 cm2, Cc increased from 0.73 (flat) to 0.87 (dome), and for an area of 0.5 cm2, from 0.62 to 0.75. For each shape, Cc increased with increasing orifice size relative to the proximal funnel (more tubelike). These variations translated into important differences of up to 40% in pressure gradient for the same anatomic area and flow rate (greatest for the flattest valves), with a corresponding variation in calculated Gorlin area (an effective area) relative to anatomic values. CONCLUSIONS: The coefficient of contraction and the related net pressure loss are importantly affected by the variations in leaflet geometry seen in patients with mitral stenosis. Three-dimensional echocardiography and stereolithography, with the use of actual information from patients, can address such uniquely three-dimensional questions to provide insight into the relations between cardiac structure, pressure, and flows.


Subject(s)
Blood Pressure , Echocardiography , Image Processing, Computer-Assisted , Lasers , Mitral Valve Stenosis/pathology , Mitral Valve Stenosis/physiopathology , Models, Cardiovascular , Myocardial Contraction , Humans
10.
J Am Soc Echocardiogr ; 9(2): 147-55, 1996.
Article in English | MEDLINE | ID: mdl-8849610

ABSTRACT

One approach to three-dimensional echocardiography is to reconstruct the surface of cardiac structures from two-dimensional images positioned in three-dimensional space. This approach has yielded accurate measures; however, the relationship between the number of nonparallel images used in three-dimensional echocardiographic reconstruction to the accuracy of the volume calculated has not been determined. With a canine model in which instantaneous left ventricular volume could be measured in vivo, images were obtained from intersecting long- and short-axis scans and stored with their spatial coordinates. The left ventricle was reconstructed and its volume calculated. The difference between three-dimensional echocardiographic and true volume was determined in 84 different cavitary volumes (4 to 85 ml). In each case, long- and short-axis images were deleted serially from the original data set (maximum of 27) until there were only three images left in the reconstruction. After each set of deletions, left ventricular volume was recalculated with the remaining images. Three-dimensional echocardiography accurately quantified ventricular volume with eight to 12 intersecting images, with a mean error of less than 1 ml and an SD of 5 ml. With a reduction of component images below eight, there were progressive increases in both absolute and mean percentage error. Accurate assessment of stroke volume and ejection fraction in this beating heart model also required eight to 12 images. Left ventricular volume and systolic function can be quantitated by three-dimensional echocardiography with as few as eight to 12 intersecting or nonparallel images.


Subject(s)
Echocardiography/methods , Stroke Volume , Analysis of Variance , Animals , Diastole , Dogs , Echocardiography/instrumentation , Echocardiography/statistics & numerical data , Heart Ventricles/diagnostic imaging , Linear Models , Reproducibility of Results , Systole , Ventricular Function
11.
Am Heart J ; 131(3): 553-9, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8604637

ABSTRACT

Recently a new acoustic-quantification (AQ) technique has been developed to provide on-line automated border detection with an integrated backscatter analysis. Prior studies have largely correlated AQ areas with volumes without direct comparison of volumes for agreement. By using complete AQ-detected borders as the input to a validated method for three-dimensional echocardiographic (3DE) reconstruction, we can compare an entire cavity volume measured with the aid of AQ against a directly measured volume. This would also explore the possibility of applying AQ to 3DE reconstruction to reduce tracing time and enhance routine applicability. To compare reconstructed volumes with actual values in a stable standard allowing direct volume measurement, the left ventricles of 13 excised animal hearts were studied with a 3DE system that automatically combines two-dimensional (2D) images and their locations. Intersecting 2D views were obtained with conventional scanning and AQ imaging, with gains optimized to permit 3D reconstruction by detecting the most continuous AQ borders for each view, with maximal cavity size. Reconstruction was performed with manually traced central endocardial reflections and AQ-detected borders visually reproduced the left ventricular shapes; the AQ reconstructions, however, were consistently smaller. The reconstructed left ventricular (LV) volumes correlated well with actual values by both manual and AQ techniques (r = 0.93 and 0.88, with standard errors of 2.3 cc and 2.0 cc, p = not significant [NS]). Agreement with actual values was relatively close for the manually traced borders (y = 0.93x + 0.68, mean difference = -0.8 +/-2.2 cc). AQ-derived reconstructions consistently underestimated LV volume by 39 +/- 10% (y = 0.62x-0.09, mean difference = -7.8 +/- 3.0 cc, different from manually traced and actual volumes by analysis of variance [ANOVA], F = 69, p<0.00001). The AQ-detected threshold signal was displaced into the cavity, and volume between walls and false tendons was excluded, leading to underestimation, which increased with increasing cavity volume (r = 0.76). The AQ technique can therefore be applied to 3DE reconstruction, providing volumes that correlate well with directly measured values in a stable in vitro standard, minimizing observer decisions regarding manual border placement after image acquisition. However, when the complete borders needed for 3D reconstruction are used, absolute volumes are underestimated with current algorithms that integrate backscatter and displace the detected threshold into the ventricular cavity.


Subject(s)
Echocardiography/methods , Stroke Volume , Animals , Echocardiography/instrumentation , Heart Ventricles/diagnostic imaging , Microcomputers , Sheep , Signal Processing, Computer-Assisted/instrumentation , Video Recording
12.
Am Heart J ; 130(4): 812-22, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7572591

ABSTRACT

To calculate left ventricular (LV) volume by two-dimensional echocardiography (2DE), assumptions must be made about ventricular symmetry and geometry. Three-dimensional echocardiography (3DE) can quantitate LV volume without these limitations, yet its incremental value over 2DE is unknown. The purpose of this study was to compare the accuracy of LV volume determination by 3DE to standard 2DE methods. To compare the accuracy of 3DE with standard 2DE algorithms for quantitating LV volume, 28 excised canine ventricles of known volume and varying shapes (15 symmetric and 13 aneurysmal) and 10 instrumented dogs prepared so that instantaneous ventricular volume could be measured were examined by 2DE (bullet and biplane Simpson's formulas) and again by 3DE. In both excised and beating hearts, 3DE was more accurate in quantitating volume than either 2DE method (excised: error = 0.6 +/- 3.2, 2.5 +/- 10.7, and 4.0 +/- 8.5 ml by 3D, bullet, and Simpson's, respectively; beating: error = -0.5 +/- 3.5, -0.3 +/- 9.6, and -7.6 +/- 8.0 ml by 3DE, bullet, and Simpson's, respectively). This difference in accuracy between 3DE and 2DE methods was especially apparent in asymmetric ventricles distorted by ischemia or right ventricular volume overload. Stroke volume and ejection fraction calculated by 3DE also demonstrated better agreement with actual values than the bullet or Simpson methods with less variability (ejection fraction: error = -2.0% +/- 5.1%, 7.7% +/- 8.5%, and 6.8% +/- 12.3% by 3DE, bullet, and Simpson's, respectively). In both in vitro and in vivo settings, 3DE provides improved accuracy for LV volume and performance than current 2DE algorithms.


Subject(s)
Cardiac Volume , Echocardiography/methods , Ventricular Function, Left , Animals , Dogs , Stroke Volume
13.
J Theor Biol ; 172(3): 245-58, 1995 Feb 07.
Article in English | MEDLINE | ID: mdl-7715195

ABSTRACT

An algorithm (HRG), developed to allow the pairwise comparisons of the aligned residues of several members of large gene families of polytopic integral membrane proteins is described. Using hydrophobicity scales, application of this algorithm allows the number and size of the membrane-spanning domains of bacteriorhodopsin, a polytopic protein whose structure has been partially determined, to be predicted with a high degree of accuracy (sensitivity 94%, specificity 82% for predicting the membrane embedded or extramembranous location of residues). As opposed to previously reported structure-prediction algorithms, delineation of putative transmembrane segments from connecting loops is also more clearly evident with the application of the HRG algorithm, even with proteins from widely divergent species. This indicates strong evolutionary pressure for the conservation of both the hydrophobic and hydrophilic character of residues in membrane-embedded regions of polytopic proteins, such as those of the G-protein-coupled receptor superfamily. These and other structural and functional implications evident from the application of the HRG algorithm are considered.


Subject(s)
Algorithms , Conserved Sequence , Membrane Proteins/genetics , Amino Acid Sequence , Bacteriorhodopsins/genetics , Membrane Proteins/metabolism , Molecular Sequence Data , Sequence Alignment , Water/metabolism
14.
Circulation ; 91(1): 222-30, 1995 Jan 01.
Article in English | MEDLINE | ID: mdl-7805206

ABSTRACT

BACKGROUND: Current two-dimensional (2D) echocardiographic measures of left ventricular (LV) volume are most limited by aneurysmal distortion, which restricts application of simple geometric models that assume symmetrical shape. 2D methods also fail to provide separate volumes of the aneurysm and nonaneurysmal residual LV cavity, which could help assess the stroke volume wasted by dyskinesis and the potential residual LV body to guide surgical approaches and predict their outcome. Three-dimensional (3D) echocardiographic reconstruction has potential advantages for assessing aneurysmal left ventricles because it is not dependent on geometric assumptions, does not require standardized views that may exclude portions of the aneurysm, and can potentially measure separate aneurysm and nonaneurysm cavity volumes of any shape. The purpose of this study was first, to validate the accuracy of 3D echocardiographic reconstruction for quantifying total LV and separate LV body and aneurysm volumes in vitro so as to provide direct standards for the separate volumes; and second, to determine the feasibility and accuracy of 3D echocardiographic reconstruction for quantifying the total volume and function of aneurysmal left ventricles in an animal model, providing a reference standard for instantaneous LV volume. METHODS AND RESULTS: A recently developed 3D system that automatically combines 2D images and their locations was applied (1) to reconstruct 10 aneurysmal ventricular phantoms and 12 gel-filled autopsied human hearts with aneurysms, comparing cavity volumes (total and aneurysm) to those measured by fluid displacement; and (2) to reconstruct the left ventricle during 19 hemodynamic stages in four dogs with surgically created LV aneurysms, comparing total volumes with actual instantaneous values measured by an intracavitary balloon attached to an external column for validation and also calculating the stroke volume wasted by aneurysmal dyskinesis. 3D reconstruction reproduced the distorted aneurysmal LV shapes. In vitro, calculated volumes (aneurysm, nonaneurysm, and total) agreed well with actual values, with correlation coefficients of .99 and SEEs of 3.2 to 6.1 cm3 for phantoms and 3.4 to 4.2 cm3 for autopsied hearts (mean error, < 4% for both). In vivo, LV end-diastolic, end-systolic, and stroke volumes as well as ejection fraction calculated by 3D echocardiography correlated well with actual values (r = .99, .99, .95, and .99, respectively) and agreed closely with them (SEE = 4.3 cm3, 3.5 cm3, 1.7 cm3, and 2%, respectively). The stroke volumes wasted by the aneurysm were -20.1 +/- 19.3% of LV body (nonaneurysm) stroke volume. CONCLUSIONS: Despite distorted ventricular shapes, a recently developed 3D echocardiographic system and surfacing algorithm can accurately reconstruct aneurysmal left ventricles and quantify total LV volume (validated in vivo and in vitro) as well as the separate volumes of the aneurysm and residual LV body (validated in vitro). This should improve our ability to evaluate such ventricles and guide surgical approaches.


Subject(s)
Echocardiography , Heart Aneurysm/diagnostic imaging , Algorithms , Animals , Dogs , Heart Aneurysm/pathology , Humans , Image Processing, Computer-Assisted , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/pathology
15.
J Am Coll Cardiol ; 24(1): 254-9, 1994 Jul.
Article in English | MEDLINE | ID: mdl-8006275

ABSTRACT

OBJECTIVES: The purpose of this study was to examine the accuracy of three-dimensional echocardiography for the quantification of asymmetric pericardial effusion volume and to compare this new technique with two-dimensional echocardiography. BACKGROUND: Quantification of pericardial effusion by two-dimensional echocardiography relies on a symmetric distribution of the fluid. Three-dimensional echocardiography can quantitate volume without these limitations, but its accuracy for pericardial effusion volume has not yet been assessed. METHODS: In six open chest dogs, 41 different asymmetrically distributed pericardial effusions of known volume were created by serial infusions of fluid through a pericardial catheter. The hearts were imaged using an automated echocardiographic method that integrates three-dimensional spatial and imaging data. The surfaces of the pericardial sac and heart were then reconstructed, and the volumes of pericardial effusions were calculated. Two-dimensional echocardiography was performed simultaneously, and volumes were calculated using the prolate ellipsoid method. Asymmetric distribution of the fluid was obtained by applying localized hydrostatic pressure to the pericardium. RESULTS: The volumes of pericardial effusion quantified using three-dimensional echocardiography correlated well with actual volumes (y = 1.0x - 1.4, SEE = 7.7 ml, r = 0.98). Two-dimensional echocardiography had an acceptable correlation (y = 1.0x + 2.3, SEE = 23 ml, r = 0.84), but a marked degree of variation from the true value was observed for any individual measurement. CONCLUSIONS: Three-dimensional echocardiography accurately quantifies pericardial effusion volume in vivo, even when the fluid is distributed asymmetrically, whereas two-dimensional echocardiography is less reliable. This new technique may be of clinical value in quantitating pericardial effusion, especially in the serial evaluation of asymmetric or loculated effusions.


Subject(s)
Echocardiography/methods , Pericardial Effusion/diagnostic imaging , Algorithms , Animals , Disease Models, Animal , Dogs , Echocardiography/instrumentation , Echocardiography/statistics & numerical data , Evaluation Studies as Topic
16.
J Am Coll Cardiol ; 23(7): 1715-22, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8195537

ABSTRACT

OBJECTIVES: This study tested the ability of three-dimensional echocardiography to reconstruct the right ventricular free wall and determine its mass in vivo using a system that automatically combines two-dimensional images with their spatial locations. BACKGROUND: Right ventricular free wall thickness is limited as an index of right ventricular hypertrophy because right ventricular mass may increase by dilation without increased thickness and because trabeculations and oblique views can exaggerate thickness in individual M-mode and two-dimensional scans. Three-dimensional echocardiography may have potential advantages because it can integrate the entire free wall mass, uninfluenced by oblique views or geometric assumptions. METHODS: The three-dimensional system was applied to 12 beating canine hearts to reconstruct the right ventricular free wall in intersecting views. The corresponding mass was compared with actual weights of the excised right ventricular free wall (15.5 to 78 g). For comparison, right ventricular sinus and outflow tract thickness were also measured by two-dimensional echocardiography, and the ability to predict mass from these values was determined. RESULTS: The three-dimensional algorithm successfully reproduced right ventricular free wall mass, which agreed well with actual values: y = 1.04x + 0.02, r = 0.985, SEE = 2.7 g (5.7% of the mean value). The two-dimensional predictions showed increased scatter: The variance of mass estimation, based on thickness, was 9.5 to 12.5 (average 11) times higher than the three-dimensional method (p < 0.02). CONCLUSIONS: Despite the irregular crescentic shape of the right ventricle, its free wall mass can be accurately measured by three-dimensional echocardiography in vivo, providing closer agreement with actual mass than predictions based on wall thickness. This method, with the increased efficiency of the three-dimensional system, can potentially improve our ability to evaluate the presence and progression of right ventricular hypertrophy.


Subject(s)
Echocardiography/methods , Heart Ventricles/diagnostic imaging , Hypertrophy, Right Ventricular/diagnostic imaging , Animals , Dogs
17.
Circulation ; 89(5): 2342-50, 1994 May.
Article in English | MEDLINE | ID: mdl-8181160

ABSTRACT

BACKGROUND: Current two-dimensional echocardiographic measures of right ventricular volume are limited by the asymmetrical and crescentic shape of the ventricle and by difficulty in obtaining standardized views. Three-dimensional echocardiographic reconstruction, which does not require geometric assumptions or standardized views, may therefore have potential advantages for determining right ventricular volume. Three-dimensional techniques, however, have not been applied to the right ventricle in vivo, where cardiac motion and contraction could affect accuracy. The purpose of this study was to determine the feasibility and accuracy of three-dimensional echocardiographic reconstruction for quantifying right ventricular volume and function in vivo. In particular, it was designed to test the accuracy of a newly developed system that provides rapid, efficient, and automated three-dimensional data collection (minimizing motion effects) and takes advantage of the full three-dimensional data set to obtain volume. METHODS AND RESULTS: The three-dimensional system was applied to reconstruct the right ventricle and measure its volume and function during 20 hemodynamic stages created in five dogs. Actual instantaneous volumes were measured continuously by an intracavitary balloon connected to an external column. Hemodynamics were varied by volume loading and induction of ischemia. Three-dimensional reconstruction successfully reproduced right ventricular volume compared with actual values at end diastole (y = 1.0 chi-3.4, r = .99, SEE = 1.8 mL) and end systole (y = 1.0 chi+ 2.0, 4 = .98, SEE = 2.5 mL). The mean difference between calculated and actual volumes throughout the cycle was 2.1 mL, or 4.9% of the mean. Ejection fraction also correlated well with actual values (y = 0.96 chi-0.3, r = .98, SEE = 3.3%). CONCLUSIONS: Despite the irregular crescentic shape of the right ventricle, this newly developed three-dimensional system and surfacing algorithm can accurately reconstruct its shape and quantitate its volume and function in vivo without geometric assumptions. The increased efficiency of the system should increase applicability to issues of clinical and research interest.


Subject(s)
Echocardiography/methods , Heart Ventricles/diagnostic imaging , Image Processing, Computer-Assisted , Ventricular Function, Right/physiology , Algorithms , Animals , Dogs , Feasibility Studies , Reproducibility of Results , Stroke Volume/physiology
18.
J Am Soc Echocardiogr ; 7(2): 150-8, 1994.
Article in English | MEDLINE | ID: mdl-8185959

ABSTRACT

Two-dimensional echocardiographic measures of right ventricular volume are limited by the asymmetric and crescentic shape of that ventricle and the difficulty in obtaining standardized views. We have developed a three-dimensional echocardiographic system that automatically integrates images and positional data and calculates right ventricular volume without the need for geometric assumptions or standardized views and a surfacing algorithm that takes advantage of the full three-dimensional data set. The accuracy of this system was studied and compared with two-dimensional methods in 12 gel-filled excised human right ventricles (18 to 74 ml). Volumes calculated by three-dimensional echocardiography correlated well with actual values (r = 0.99) and agreed more closely with them than did those obtained by two-dimensional methods (p < 0.02).


Subject(s)
Algorithms , Echocardiography/methods , Image Processing, Computer-Assisted , Ventricular Function, Right , Heart Ventricles/diagnostic imaging , Humans , In Vitro Techniques , Reproducibility of Results
19.
J Am Coll Cardiol ; 23(1): 201-8, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8277082

ABSTRACT

OBJECTIVES: The purpose of this study was to demonstrate the feasibility of in vivo three-dimensional reconstruction of ventricular septal defects and to validate its quantitative accuracy for defect localization in excised hearts (used to permit comparison of three-dimensional and direct measurements without cardiac contraction). BACKGROUND: Appreciating the three-dimensional spatial relations of ventricular septal defects could be useful in planning surgical and catheter approaches. Currently, however, echocardiography provides only two-dimensional views, requiring mental integration. A recently developed system automatically combines two-dimensional echocardiographic images with their spatial locations to produce a three-dimensional construct. METHODS: Surgically created ventricular septal defects of varying size and location were imaged and reconstructed, along with the left and right ventricles, in the beating heart of six dogs to demonstrate the in vivo feasibility of producing a coherent image of the defect that portrays its relation to surrounding structures. Two additional gel-filled excised hearts with defects were completely reconstructed. Quantitative localization of the defects relative to other structures (ventricular apexes and valve insertions) was then validated for seven defects in excised hearts. The right septal margins of the exposed defects were also traced and compared with their reconstructed areas and circumferences. RESULTS: The three-dimensional images provided coherent images and correct spatial appreciation of the defects (two inlet, two trabecular, one outlet and one membranous Gerbode in vivo; one inlet and one apical in excised hearts). The distances between defects and other structures in the excised hearts agreed well with direct measures (y = 1.05x-0.18, r = 0.98, SEE = 0.30 cm), as did reconstructed areas (y = 1.0x-0.23, r = 0.98, SEE = 0.21 cm2) and circumferences (y = 0.97x + 0.13, r = 0.97, SEE = 0.3 cm). CONCLUSIONS: Three-dimensional reconstruction of ventricular septal defects can be achieved in the beating heart and provides an accurate appreciation of defect size and location that could be of value in planning interventions.


Subject(s)
Echocardiography/methods , Heart Septal Defects, Ventricular/diagnostic imaging , Image Processing, Computer-Assisted/methods , Animals , Disease Models, Animal , Dogs , Reproducibility of Results
20.
Circulation ; 88(4 Pt 1): 1715-23, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8403317

ABSTRACT

BACKGROUND: Current two-dimensional quantitative echocardiographic methods of volume assessment require image acquisition from standardized scanning planes. Left ventricular volume and ejection fraction are then calculated by assuming ventricular symmetry and geometry. These assumptions may not be valid in distorted ventricles. Three-dimensional echocardiography can quantify left ventricular volume without the limitations imposed by the assumptions of two-dimensional methods. We have developed a three-dimensional system that automatically integrates two-dimensional echocardiographic images and their positions in real time and calculates left ventricular volume directly from traced endocardial contours without geometric assumptions. METHODS AND RESULTS: To study the accuracy of this method in quantifying left ventricular volume and performance in vivo, a canine model was developed in which instantaneous left ventricular volume can be measured directly with an intracavitary balloon connected to an external column. Ten dogs were studied at 84 different cavity volumes (4 to 85 cm3) and in conditions of altered left ventricular shape produced by either coronary occlusion or right ventricular volume overload. To demonstrate clinical feasibility, 19 adult human subjects were then studied by this method for quantification of stroke volume. Left ventricular volume, stroke volume, and ejection fraction calculated by three-dimensional echocardiography correlated well with directly measured values (r = .98, .96, .96 for volume, stroke volume, and ejection fraction, respectively) and agreed closely with them (mean difference, -0.78 cm3, -0.60 cm3, -0.32%). In humans, there was a good correlation (r = .94, SEE = 4.29 cm3) and agreement (mean difference, -0.98 +/- 4.2 cm3) between three-dimensional echocardiography and Doppler-derived stroke volumes. CONCLUSIONS: Three-dimensional echocardiography allows accurate assessment of left ventricular volume and systolic function.


Subject(s)
Echocardiography/methods , Image Processing, Computer-Assisted , Ventricular Function, Left/physiology , Adult , Animals , Dogs , Female , Humans , Male , Myocardial Contraction/physiology , Stroke Volume/physiology
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