Leng Jiang

Insights From Three-Dimensional Echocardiography Into the Mechanism of Functional Mitral Regurgitation Direct In Vivo Demonstration of Altered Leaflet Tethering Geometry

BACKGROUNDnRecent 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.nnnMETHODS AND RESULTSnWe 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)).nnnCONCLUSIONSnLV 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.

Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation

OBJECTIVESnThis 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.nnnBACKGROUNDnDysfunction and dilation-both mechanisms with practical therapeutic implications-are difficult to separate in patients.nnnMETHODSnIn 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnSegmental 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.

An integrated mechanism for systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy based on echocardiographic observations

Although many mechanisms have been proposed to explain systolic anterior motion (SAM) of the mitral valve in hypertrophic cardiomyopathy, the precise mechanism of its onset and cessation remain undefined. The Venturi theory, based on increased flow velocity in a narrowed outflow tract, is widely accepted but fails to explain several important characteristics of SAM. It also neglects the potential role of drag forces generated by interposition of the leaflets into the path of ejection and of factors that would decrease the effectiveness of papillary muscle restraint. In order to obtain further insight into the mechanism of SAM, a detailed geometric study of the left ventricle and mitral apparatus was performed with cross-sectional echocardiography in three equal-sized groups of patients with hypertrophic cardiomyopathy and SAM, patients with hypertrophy and no anterior motion, and normal control subjects. A salient finding was that SAM began prior to ejection in patients with hypertrophic cardiomyopathy, which cannot be explained by the Venturi theory. Further, SAM began and was most prominent in the central portion of the leaflet as opposed to its lateral edges; this finding is not predicted by the Venturi mechanism. In addition to outflow tract narrowing, other structural changes unique to patients with SAM included anterior and inward displacement of the papillary muscles, anterior displacement of the mitral leaflets, and elongation of the mitral leaflets, which were, on the average, 1.5 to 1.7 cm longer than in the other subjects (p less than 0.0001). On the basis of these observations, an integrated mechanism for the initiation and resolution of SAM is proposed that would explain observed features such as onset before ejection and central prominence. This mechanism combines the effects of outflow tract narrowing with those of papillary muscle displacement. In particular, anterior and inward displacement of the papillary muscles can be predicted to alter the effectiveness of chordal support so that the central leaflet portions become relatively slack and are more readily displaced anteriorly. The altered distribution of chordal tension can also be predicted to orient the distal leaflets upward into the outflow tract at the onset of systole, prior to aortic valve opening, so that ventricular ejection will actually drag the interposed leaflets anteriorly. The resolution of SAM can be understood in terms of a reverse Venturi effect created by mitral regurgitation, as well as continued traction of the centrally displaced papillary muscles on the lateral leaflet margins.(ABSTRACT TRUNCATED AT 400 WORDS)

Variable effects of changes in flow rate through the aortic, pulmonary and mitral valves on valve area and flow velocity: Impact on quantitative doppler flow calculations

Doppler echocardiographic methods for measuring volumetric flow through the aortic, pulmonary and mitral valves provide the cardiologist with several potentially interchangeable noninvasive methods for determining cardiac output. In addition, comparison of flow differences through individual valves offers the potential to quantitate shunt flow and regurgitant volumes. To date, however, no study has compared the relative accuracies of each of these flow measurements in a controlled experimental setting. Therefore, in this study, Doppler echocardiography was used to measure aortic, pulmonary and mitral valve flows in seven open chest dogs on right atrial bypass where forward cardiac output was precisely controlled with a roller pump. Correlations with roller pump output were better for Doppler measurements of aortic (r = 0.98, SD = 0.3) and mitral (r = 0.97, SD = 0.3) than for pulmonary (r = 0.93, SD = 0.5) valve flow. Interobserver reproducibility was also better for aortic (r = 0.94) and mitral (r = 0.97) than for pulmonary (r = 0.88) valve flow measurements. All valves showed flow-related increases in cross-sectional area, but the slope of this response was variable: 0.05, 0.16 and 0.21 for the aortic, the pulmonary and the mitral valve, respectively. Increased forward flow through the aortic valve, therefore, was manifested primarily by an increase in velocity, whereas increasing flow through the pulmonary and mitral valves produced more significant area changes with correspondingly smaller increases in the velocity component. Recalculation of Doppler-determined outputs, assuming a fixed valve area for the entire range of flows, resulted in a decreased correlation with roller pump output. Both velocity and valve area should be measured at each flow rate for greatest accuracy in volumetric flow calculations.

Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering

OBJECTIVESnWe tested the hypothesis that patients with incomplete systolic mitral leaflet closure (IMLC: apically displaced coaptation) also have restricted diastolic leaflet opening that is independent of mitral inflow volume and provides evidence supporting increased leaflet tethering.nnnBACKGROUNDnCompeting hypotheses for functional mitral regurgitation (MR) with IMLC include global left ventricular (LV) dysfunction per se (reduced leaflet closing force) versus geometric distortion of the mitral apparatus by LV dilation (augmented leaflet tethering). These are inseparable in systole, but restricted leaflet motion has also been observed in diastole, and attributed to reduced mitral inflow.nnnMETHODSnDiastolic mitral leaflet excursion and orifice area were measured by two-dimensional echocardiography in 58 patients with global LV dysfunction, 36 with and 22 without IMLC, compared with 21 normal subjects. The biplane Simpsons method was used to calculate LV ejection volume, which equals mitral inflow volume in the absence of aortic regurgitation.nnnRESULTSnThe diastolic mitral leaflet excursion angle was markedly reduced in patients with IMLC compared with those without IMLC, whose ventricles were smaller, and normal subjects (17 +/- 10 degrees vs. 58 +/- 13 degrees vs. 67 +/- 8 degrees, p < 0.0001). Excursion angle was dissociated from mitral inflow volume (r2 = 0.04); excursion was reduced in patients with IMLC despite a normal inflow volume in the larger ventricles with MR (60 +/- 25 vs. 61 +/- 12 ml in normal subjects, p = NS), and excursion was nearly normal in patients without IMLC despite reduced inflow volume (40 +/- 10 ml, p < 0.001 vs. normal subjects). The anterior leaflet when maximally open coincided well with the line connecting its attachments to the anterior annulus and papillary muscle tip (angular difference = 3 +/- 7 degrees vs. 25 +/- 9 degrees vs. 32 +/- 10 degrees in patients with and without IMLC vs. normal subjects, p < 0.0001). In patients with IMLC, the leaflet tip orifice was smaller in an anteroposterior direction but wider than in the other groups, giving a normal total area (6.8 +/- 1.8 vs. 7.1 +/- 1.2 vs. 6.9 +/- 0.8 cm2, p = NS).nnnCONCLUSIONSnPatients with LV dysfunction and systolic IMLC also have restricted diastolic leaflet excursion that is independent of inflow volume, coincides with the tethering line connecting the annulus and papillary muscle and reflects limitation of anterior motion relative to the posteriorly placed papillary muscles without a decrease in total orifice area. These observations are consistent with increased tethering by displaced mitral leaflet attachments in the dilated ventricles of patients with IMLC that can restrict both diastolic opening and systolic closure.

Quantitative Three-Dimensional Reconstruction of Aneurysmal Left Ventricles In Vitro and In Vivo Validation

BACKGROUNDnCurrent 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.nnnMETHODS AND RESULTSnA 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.nnnCONCLUSIONSnDespite 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.

Echocardiographic Assessment of Right Ventricular Volume and Function

Echocardiographic evaluation of right ventricular volume and function has become a subject of growing interest with the increasing awareness of the important role of the right ventricle in the entire circulation. However, the anatomically complex and load‐dependent shaped right ventricle shape is difficult to describe by a simple geometric figure and its volume and function are, therefore, difficult to assess in a simple manner. A number of echocardiographic methods for evaluating right ventricular volume and function have emerged; to date, however, their quantification remains a clinical challenge. The major goal is to develop a reproducible method that will allow for quantitative comparisons between patients or serially within a given patient. This discussion examines the available methods with specific attention to their reliability and limitations. Visual inspection or measurement of single plane indices is limited by their lack of standardization and failure to describe the entire right ventricle. Simpsons rule requires computer calculations and assumes an elliptic symmetry present in the left, but not the right ventricle. Application of the area‐length method to the subcostal outflow tract and apical four‐chamber views is a particularly practical current approach. Three‐dimensional echo reconstruction, which eliminates the need for geometric assumptions and individual standardized views, although only in its infancy, promises to be the most accurate method for right ventricular volume calculation and in the future should emerge as the standard for research and many clinical applications.

A Doppler-two-dimensional echocardiographic method for quantitation of mitral regurgitation.

A noninvasive method to accurately quantitate the severity of mitral insufficiency would be of major clinical value. In theory, in the absence of confounding variables, regurgitant mitral flow should represent the difference between forward mitral blood flow and aortic blood flow. Since Doppler-two-dimensional echocardiographic (D2DE) methods for measuring transvalvular mitral and aortic flow have been validated, it should be possible to use mitral and aortic flows derived by this method to calculate regurgitant mitral flow. To assess the validity and accuracy of this combined approach for quantitation of regurgitant flow, we developed an open-chest canine preparation in which we could simulate, vary, and accurately measure degrees of mitral regurgitation. Seven animals were anesthetized and prepared to allow controlled right heart output. Mitral regurgitation was than simulated by placing a flexible conduit incorporating a one-way valve and electromagnetic flowmeter between the left ventricular apex and left atrium. Flow through the tube (effective mitral regurgitation) was varied between 0.2 and 1.8 liters/min and forward cardiac output ranged between 0.5 and 4 liters/min. Transmitral and transaortic flows were calculated by previously reported Doppler methods. Doppler-derived estimates of forward flow through the aortic valve correlated well with the flow measured by flowmeter (r = .92), and regurgitant flow and regurgitant fraction calculated by the D2DE approach also compared well with those measured by flowmeter (r = .84 and .83, respectively). This study demonstrates that mitral regurgitant flow and regurgitant fraction calculated by the D2DE method provide an acceptable measure of both absolute regurgitant flow and the regurgitant fraction in the experimental setting.

Three-dimensional Echocardiographic Reconstruction of Right Ventricular Volume: In Vitro Comparison With Two-Dimensional Methods

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).

Three-dimensional echocardiography: In vivo validation for right ventricular free wall mass as an index of hypertrophy

OBJECTIVESnThis 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.nnnBACKGROUNDnRight 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.nnnMETHODSnThe 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnDespite 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.