Katherine J. Middleton

Doppler Tissue Imaging: A Noninvasive Technique for Evaluation of Left Ventricular Relaxation and Estimation of Filling Pressures

OBJECTIVES This investigation was designed 1) to assess whether the early diastolic velocity of the mitral annulus (Ea) obtained with Doppler tissue imaging (DTI) behaves as a preload-independent index of left ventricular (LV) relaxation; and 2) to evaluate the relation of the mitral E/Ea ratio to LV filling pressures. BACKGROUND Recent observations suggest that Ea is an index of LV relaxation that is less influenced by LV filling pressures. METHODS One hundred twenty-five study subjects were classified into three groups according to mitral E/A ratio, LV ejection fraction (LVEF) and clinical symptoms: 34 asymptomatic subjects with a normal LVEF and an E/A ratio > or =1; 40 with a normal LVEF, an E/A ratio <1 and no heart failure symptoms (impaired relaxation [IR]); and 51 with heart failure symptoms and an E/A ratio >1 (pseudonormal [PN]). Ea was derived from the lateral border of the annulus. A subset of 60 patients had invasive measurement of pulmonary capillary wedge pressure (PCWP) simultaneous with Doppler echocardiographic DTI. RESULTS Ea was reduced in the IR and PN groups compared with the group of normal subjects: 5.8 +/- 1.5 and 5.2 +/- 1.4 vs. 12 +/- 2.8 cm/s, respectively (p < 0.001). Mean PCWP (20 +/- 8 mm Hg) related weakly to mitral E (r = 0.68) but not to Ea. The E/Ea ratio related well to PCWP (r = 0.87; PCWP = 1.24 [E/Ea] + 1.9), with a difference between Doppler and catheter measurements of 0.1 +/- 3.8 mm Hg. CONCLUSIONS Ea behaves as a preload-independent index of LV relaxation. Mitral E velocity, corrected for the influence of relaxation (i.e., the E/Ea ratio), relates well to mean PCWP and may be used to estimate LV filling pressures.

Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler.

OBJECTIVES Our goal was to identify the hemodynamic determinants of the mitral annulus (MA) diastolic velocities by tissue Doppler. BACKGROUND The MA diastolic velocities are promising indexes of left ventricular (LV) diastolic function. However, their hemodynamic determinants have not yet been evaluated. METHODS Ten adult mongrel dogs underwent left atrial (LA) and LV pressure measurements by Millar catheters while tissue Doppler was applied to record the MA diastolic velocities at the septal and lateral comers. Conventional transmitral flow was also obtained. Left atrial and LV pressures were modified utilizing fluid administration and caval occlusion, whereas dobutamine and esmolol were used to change LV and LA relaxation. Left ventricular filling pressures were altered during different lusitropic states to evaluate for the possible interaction of preload and LV relaxation on the early diastolic velocity (Ea). RESULTS In the majority of dogs, a positive significant relation was observed between Ea and the transmitral pressure gradient (r = 0.57, p = 0.04). The Ea had strong correlations with tau (r = -0.83, p < 0.001), LV -dP/dt (r = 0.8, p < 0.001) and minimal LV pressure (r = -0.76, p < 0.01). However, there was no relation between Ea and the transmitral pressure gradient in experimental stages where tau >50 ms. Furthermore, the late diastolic velocity at both corners of the MA had significant positive relations with LA dP/dt (r = 0.67, p < 0.01) and LA relaxation (r = 0.73, p < 0.01) but an inverse correlation with LV end-diastolic pressure (r = -0.53, p = 0.01). CONCLUSIONS Left ventricular relaxation, minimal pressure and preload determine Ea while late diastolic velocity determinants include LA dP/dt, LA relaxation and LV end-diastolic pressure.

Avoiding Papillary Muscle Infarction With Myocardial Contrast Echocardiographic Guidance of Nonsurgical Septal Reduction Therapy for Hypertrophic Obstructive Cardiomyopathy

Intracoronary myocardial contrast echocardiography (MCE) can be used to guide the delivery of ethanol during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. The echocardiographic contrast agent is injected immediately before the injection of ethanol, down the lumen of the inflated balloon that resides in the target septal coronary artery. This is the artery that supplies the area of the septum involved with the mitral leaflet(s) in causing dynamic outflow tract obstruction. MCE provides a direct visualization of the myocardial territory that should receive ethanol and consequently undergo infarction. In rare instances, the cannulated vessel does not supply the culprit septal segment(s) but supplies instead …

Doppler Estimation of Left Ventricular Filling Pressures in Patients With Hypertrophic Cardiomyopathy

BACKGROUND Conventional Doppler parameters are unreliable for estimating left ventricular (LV) filling pressures in hypertrophic cardiomyopathy (HCM). This study was undertaken to evaluate flow propagation velocity by color M-mode and early diastolic annular velocity (Ea) by tissue Doppler 2 new indices of LV relaxation, combined with mitral E velocity for estimation of filling pressures in HCM. METHODS AND RESULTS Thirty-five HCM patients (52+/-15 years) underwent LV catheterization simultaneously with 2-dimensional and Doppler echocardiography. Pulsed Doppler echocardiography of mitral and pulmonary venous flows was obtained along with flow propagation velocity and Ea. LV preA pressure had weak or no relations with mitral, pulmonary venous velocities and atrial volumes. In contrast, preA pressure related strongly to E velocity/flow propagation velocity (r=0.67; SEE=4) and E/Ea (r=0.76; SEE=3.4). In 17 patients with repeat measurements, preA pressure changes were well detected by measuring E velocity/flow propagation velocity (r=0.68; P=0.01) or E/Ea (r=0.8; P<0.001). PreA pressure estimation with these 2 methods was tested prospectively in 17 additional HCM patients with good results (E velocity/flow propagation velocity, r=0.76; E/Ea, r=0.82). CONCLUSIONS LV filling pressures can be estimated with reasonable accuracy in HCM patients by measuring E velocity/flow propagation velocity or E/Ea. These ratios also track changes in filling pressures.

Estimation of left and right ventricular filling pressures after heart transplantation by tissue Doppler imaging.

Current Doppler methods have been unreliable in estimating filling pressures in heart transplants. Tissue Doppler imaging is a technique that permits evaluation of myocardial relaxation; combined with transvalvular E velocity, it could improve estimation of these pressures. To investigate this possibility, we evaluated 50 patients by right-sided cardiac catheterization and Doppler echocardiography simultaneously. Their mean +/-SD age was 53+/-15 years and the mean age of donor hearts was 30+/-12.5 years. The mitral E velocity was combined with the early myocardial relaxation (Ea) velocity by tissue Doppler at the lateral border of the mitral annulus. Likewise, the tricuspid E velocity was combined with Ea at the lateral corner of the tricuspid annulus. Mean wedge pressure related weakly to mitral inflow variables but strongly to E/Ea [r=0.8; wedge pressure=2.6+1.46(E/Ea)]. In 25 repeat right-sided cardiac catheterizations, changes in mean wedge pressure were well detected by Doppler, with a mean difference of -0.7+/-3 mm Hg. Mean right atrial pressure related weakly to routine tricuspid inflow variables but strongly to tricuspid E/Ea [r=0.79; n=38; right atrial pressure=1.76(E/Ea) - 3.7]. In 18 repeat right-sided cardiac catheterizations, changes in mean right atrial pressure were well detected by Doppler, with a mean difference of 0+/-3.45 mm Hg. Mean wedge pressure and mean right atrial pressure can be estimated in heart transplants with reasonable accuracy using the ratio of E/Ea. Furthermore, this method can accurately track changes in filling pressures.

Role of myocardial contrast echocardiography during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy

OBJECTIVES This study was undertaken to evaluate the ability of myocardial contrast echocardiography (MCE) to guide the targeted delivery of ethanol during nonsurgical septal reduction therapy (NSRT) and to assess the relation between the MCE risk area and infarct size determined by enzymatic and radionuclide methods. BACKGROUND NSRT with intracoronary ethanol is a new promising treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM). Proper localization and quantification of the septal infarct before ethanol injection are highly desirable. MCE can provide accurate delineation of the vascular territory of the coronary arteries. METHODS Twenty-nine patients with HOCM and maximal medical therapy underwent NSRT. The left ventricular outflow tract (LVOT) gradient by Doppler echocardiography at baseline was 53 +/- 16 mm Hg (mean +/- SD). Before NSRT, MCE was performed in all patients with intracoronary sonicated albumin (Albunex). Diluted sonicated albumin (Albunex) was selectively injected into the septal perforator arteries during simultaneous transthoracic imaging. Immediately after MCE, ethanol was injected into the same vessel. Plasma total creatine kinase (CK), total CK-MB fraction and CK-MB fraction subforms were measured at baseline and serially for 36 h. RESULTS LVOT gradient decreased to 12 +/- 6 mm Hg (p < 0.001) after NSRT. Accurate mapping of the vascular beds of the septal perforators was successfully attained in all patients by MCE. Furthermore, the MCE risk area correlated well with peak CK (r = 0.79, p < 0.001). Six weeks after NSRT, 23 patients underwent myocardial perfusion studies performed with single-photon emission computed tomography (SPECT). Mean SPECT septal perfusion defect size involved 9.5 +/- 6% of the left ventricle and correlated well with MCE area (r = 0.7), with no statistically significant difference between the risk area estimated by MCE and that by SPECT. CONCLUSIONS Estimation of the size of the septal vascular territory with MCE is accurate, safe and feasible in essentially all patients during NSRT. MCE can delineate the perfusion bed of the septal perforators and can predict the infarct size that follows ethanol injection.

Changes in left ventricular filling and left atrial function six months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy

OBJECTIVES The purpose of this study was to evaluate changes in left ventricular (LV) filling, left atrial (LA) volumes and function six months after nonsurgical septal reduction therapy (NSRT) for hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND Patients with HOCM frequently have enlarged left atria, which predisposes them to atrial fibrillation. Nonsurgical septal reduction therapy results in significant reduction in left ventricular outflow tract (LVOT) obstruction and symptomatic improvement. However, its effect on LV passive filling volume, LA volumes and function is not yet known. METHODS Thirty patients with HOCM underwent treadmill exercise testing as well as 2-dimensional and Doppler echocardiography before and six months after NSRT. Data included clinical status, exercise duration, LVOT gradient, mitral regurgitant (MR) volume, LV pre-A pressure and LA volumes. Left atrial ejection force and kinetic energy (KE) were computed noninvasively and were compared with 12 age-matched, normal subjects. RESULTS New York Heart Association (NYHA) class was lower and exercise duration was longer (p < 0.05) six months after NSRT. The LVOT gradient, MR volume and LV pre-A pressure were all significantly reduced. HOCM patients had larger atria, which had a higher ejection force and KE, compared with normal subjects (p < 0.01). After NSRT, LV passive filling volume increased (p < 0.01), whereas LA volumes, ejection force and KE decreased (p < 0.01). Reduction in LA maximal volume was positively related to changes in LV pre-A pressure (r = 0.8, p < 0.05) and MR volume (0.4, p < 0.05). Changes in LA ejection force were positively related to changes in LA pre-A volume (r = 0.7, p < 0.01) and KE (r = 0.81, p < 0.01). The increase in exercise duration paralleled the increase in LV passive filling volume (r = 0.85, p < 0.05). CONCLUSIONS Nonsurgical septal reduction therapy results in an increase in LV passive filling volume and a reduction in LA size, ejection force and KE.

Changes in Left Ventricular Diastolic Function 6 Months After Nonsurgical Septal Reduction Therapy for Hypertrophic Obstructive Cardiomyopathy

BACKGROUND Nonsurgical septal reduction therapy (NSRT) decreases left ventricular outflow tract (LVOT) gradient and improves symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). NSRT effects on LV/left ventricular diastolic function are currently unknown. METHODS AND RESULTS HOCM patients (n=29) had Doppler echocardiography at baseline and 6 months after NSRT to evaluate changes in LV volume, pre-A-wave pressure, early diastolic mitral annulus velocity (Ea) by tissue Doppler, and tau. At 6 months, a significant reduction in LVOT gradient (from 53.6+/-15 to 6+/-5 mm Hg; P<0.001) was accompanied by improvement in exercise duration (from 284+/-147 to 408+/-178 seconds; P=0.04) and New York Health Association class (from III to I; P<0.001). Pre-A pressure (18+/-6 to 14+/-5 mm Hg; P<0.01) and tau (62+/-8 to 51+/-8 ms; P<0.01) decreased, whereas Ea (5.8+/-1.8 to 8+/-1.8 cml/s; P<0.01) and LV end-diastolic volume (117+/-16 to 130+/-22 mL; P<0.01) increased. CONCLUSIONS NSRT improves LV relaxation and compliance, which contributes to the symptomatic relief seen at 6 months.

Echocardiographic insights into the mechanisms of relief of left ventricular outflow tract obstruction after nonsurgical septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy

OBJECTIVES We sought to evaluate the mechanisms by which nonsurgical septal reduction therapy (NSRT) reduces left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM) both acutely and on a long-term basis. BACKGROUND NSRT reduces LVOT obstruction in patients with HOCM and leads to symptomatic improvement. The mechanisms involved, however, are not well studied. METHODS An initial group of 30 HOCM patients (age 46 +/- 17, 16 women) who underwent NSRT had echocardiographic studies performed at baseline and six months after the procedure. Measurements included LVOT diameter, end-diastolic distance between the anterior mitral leaflet and interventricular septum, septal base function and the angle between LV systolic flow and the protruding mitral leaflets. In addition, pulse Doppler recordings at a point 2.5 cm apical to the mitral valve were acquired and analyzed for peak and mean ejection velocity, peak acceleration rate and the ratio of acceleration time to ejection time (AT/ET). RESULTS Significant changes were observed after the procedure, with widening in the LVOT, thinning and akinesis of the septal base, decrease in the angle between LV systolic flow and the protruding mitral leaflets, a decrease in peak acceleration rate and an increase in AT/ET. All of these variables had significant relations with the decrease in LVOT obstruction (r = 0.5 to 0.79, p < 0.01). These correlations were then evaluated in a test group of 15 patients who underwent echocardiographic examinations at baseline, acutely in the catheterization laboratory with ethanol injection and at six weeks post NSRT. Acute changes in peak acceleration rate (r = 0.65) and AT/ET (r = 0.73) related significantly (p < 0.01) to the decrease in LVOT obstruction with ethanol. At six weeks, changes similar to those noted in the initial group were observed in LVOT geometry, the angle between LV systolic flow and the protruding mitral leaflets, peak acceleration rate and AT/ET. In both populations combined, these parameters accounted for 72% to 77% of the variance in gradient reduction. CONCLUSIONS Changes in LV ejection dynamics and septal base function account in part for the acute relief of LVOT gradient after NSRT. The long-term relief of obstruction is dependent on remodeling of LVOT as well as the changes in LV ejection.

Acute Effect of Nonsurgical Septal Reduction Therapy on Regional Left Ventricular Asynchrony in Patients With Hypertrophic Obstructive Cardiomyopathy

Background—Patients with hypertrophic obstructive cardiomyopathy have left ventricular (LV) diastolic dysfunction due, in part, to temporal heterogeneity in regional function. The acute effect of the relief of LV outflow tract obstruction is unknown. Therefore, we investigated the effects of nonsurgical septal reduction therapy (NSRT) on regional function. Methods and Results—Twenty-two patients (aged 56±17 years) underwent echocardiographic examination, including tissue Doppler imaging, simultaneously with left heart catheterization before and after NSRT. LV regional function was assessed in 12 segments from which myocardial strain was obtained. Asynchrony was calculated as the coefficient of variation of the time interval from the QRS complex to the onset of expansion and to early diastolic strain. After NSRT, a significant reduction in LV outflow tract obstruction (from 57±5 to 12±3 mm Hg) occurred with shortening of the time constant of LV relaxation (71±4 to 61±3 ms; both P <0.05). The coefficient of variation of the time interval to onset of regional expansion decreased significantly and related well to the changes in the time constant of LV relaxation (r =0.81, P <0.01). Conclusions—NSRT has a favorable effect on LV regional asynchrony, which accounts for the acute changes in LV relaxation.