Noah Liel-Cohen

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

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.

Design of a New Surgical Approach for Ventricular Remodeling to Relieve Ischemic Mitral Regurgitation Insights From 3-Dimensional Echocardiography

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.

Dietary Intervention to Reverse Carotid Atherosclerosis

Background— It is currently unknown whether dietary weight loss interventions can induce regression of carotid atherosclerosis. Methods and Results— In a 2-year Dietary Intervention Randomized Controlled Trial–Carotid (DIRECT-Carotid) study, participants were randomized to low-fat, Mediterranean, or low-carbohydrate diets and were followed for changes in carotid artery intima-media thickness, measured with standard B-mode ultrasound, and carotid vessel wall volume (VWV), measured with carotid 3D ultrasound. Of 140 complete images of participants (aged 51 years; body mass index, 30 kg/m2; 88% men), higher baseline carotid VWV was associated with increased intima-media thickness, age, male sex, baseline weight, blood pressure, and insulin levels (P<0.05 for all). After 2 years of dietary intervention, we observed a significant 5% regression in mean carotid VWV (−58.1 mm3; 95% confidence interval, −81.0 to −35.1 mm3; P<0.001), with no differences in the low-fat, Mediterranean, or low-carbohydrate groups (−60.69 mm3, −37.69 mm3, −84.33 mm3, respectively; P=0.28). Mean change in intima-media thickness was −1.1% (P=0.18). A reduction in the ratio of apolipoprotein B100 to apolipoprotein A1 was observed in the low-carbohydrate compared with the low-fat group (P=0.001). Participants who exhibited carotid VWV regression (mean decrease, −128.0 mm3; 95% confidence interval, −148.1 to −107.9 mm3) compared with participants who exhibited progression (mean increase, +89.6 mm3; 95% confidence interval, +66.6 to +112.6 mm3) had achieved greater weight loss (−5.3 versus −3.2 kg; P=0.03), greater decreases in systolic blood pressure (−6.8 versus −1.1 mm Hg; P=0.009) and total homocysteine (−0.06 versus +1.44 &mgr;mol/L; P=0.04), and a higher increase of apolipoprotein A1 (+0.05 versus −0.00 g/L; P=0.06). In multivariate regression models, only the decrease in systolic blood pressure remained a significant independent modifiable predictor of subsequent greater regression in both carotid VWV (β=0.23; P=0.01) and intima-media thickness (β=0.28; P=0.008) levels. Conclusions— Two-year weight loss diets can induce a significant regression of measurable carotid VWV. The effect is similar in low-fat, Mediterranean, or low-carbohydrate strategies and appears to be mediated mainly by the weight loss–induced decline in blood pressure. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique Identifier: NCT00160108.

Echocardiographic determination of risk area size in a murine model of myocardial ischemia

Genetically altered mice are useful to understand cardiac physiology. Myocardial contrast echocardiography (MCE) assesses myocardial perfusion in humans. We hypothesized it could evaluate murine myocardial perfusion before and after acute coronary ligation. MCE was performed before and after this experimental myocardial infarction (MI) in anesthetized mice by intravenous injection of contrast microbubbles and transthoracic echo imaging. Time-video intensity curves were obtained for the anterior, lateral, and septal myocardial walls. After MI, MCE defects were compared with the area of no perfusion measured by Evans blue staining. In healthy animals, intramyocardial contrast was visualized in all the cardiac walls. The anterior wall had a higher baseline video intensity (53 ± 17 arbitrary units) than the lateral (34 ± 13) and septal (27 ± 13) walls ( P < 0.001) and a lower increase in video intensity after contrast injection [50 ± 17 vs. 60 ± 24 (lateral) and 65 ± 29 (septum), P < 0.01]. After MI, left ventricular (LV) dimensions were enlarged, and the shortening fraction was decreased. A perfusion defect was imaged with MCE in every mouse, with a correlation between MCE perfusion defect size (35 ± 13%) and the nonperfused area by Evans blue (37 ± 16%, y = 0.77 x + 6.1, r = 0.93, P < 0.001). Transthoracic MCE is feasible in the mouse and can accurately detect coronary occlusions and quantitate nonperfused myocardium.Genetically altered mice are useful to understand cardiac physiology. Myocardial contrast echocardiography (MCE) assesses myocardial perfusion in humans. We hypothesized it could evaluate murine myocardial perfusion before and after acute coronary ligation. MCE was performed before and after this experimental myocardial infarction (MI) in anesthetized mice by intravenous injection of contrast microbubbles and transthoracic echo imaging. Time-video intensity curves were obtained for the anterior, lateral, and septal myocardial walls. After MI, MCE defects were compared with the area of no perfusion measured by Evans blue staining. In healthy animals, intramyocardial contrast was visualized in all the cardiac walls. The anterior wall had a higher baseline video intensity (53 +/- 17 arbitrary units) than the lateral (34 +/- 13) and septal (27 +/- 13) walls (P < 0.001) and a lower increase in video intensity after contrast injection [50 +/- 17 vs. 60 +/- 24 (lateral) and 65 +/- 29 (septum), P < 0.01]. After MI, left ventricular (LV) dimensions were enlarged, and the shortening fraction was decreased. A perfusion defect was imaged with MCE in every mouse, with a correlation between MCE perfusion defect size (35 +/- 13%) and the nonperfused area by Evans blue (37 +/- 16%, y = 0.77x + 6.1, r = 0.93, P < 0. 001). Transthoracic MCE is feasible in the mouse and can accurately detect coronary occlusions and quantitate nonperfused myocardium.

Three-Dimensional Echocardiographic Assessment of Left Ventricular Wall Motion Abnormalities in Mouse Myocardial Infarction

We applied 3-dimensional echocardiographic reconstruction to assess left ventricular (LV) volumes, function, and the extent of wall motion abnormalities in a murine model of myocardial infarction (MI). Consecutive parasternal short-axis planes were obtained at 1-mm intervals with a 13-MHz linear array probe. End-diastolic and end-systolic LV volumes were calculated by Simpsons rule, and the ejection fraction and cardiac output were derived. Echocardiography-derived cardiac output was validated by an aortic flow probe in 6 mice. Echocardiography was then performed in 9 mice before and after the left anterior descending coronary artery was ligated. Wall motion was assessed, and the ratio of the abnormally to normally contracting myocardium was calculated. After MI occurred, LV end-diastolic volume and LV end-systolic volume increased (33 +/- 10 vs 24 +/- 6 microL, P <.05 and 24 +/- 9 vs 10 +/- 4 microL, P <.001), whereas cardiac output decreased (4.2 +/- 1.5 mL/min vs 6.6 +/- 2.3 mL/min, P <.01). Forty percent of the myocardium was normokinetic, 24% was hypokinetic, and 36% was akinetic. Echocardiography can measure LV volumes and regional and global function in a murine model of myocardial infarction, thereby providing the potential to quantitate and compare the responses of various transgenic mice to MI and its therapies.

Determination of Right Ventricular Structure and Function in Normoxic and Hypoxic Mice A Transesophageal Echocardiographic Study

BACKGROUND Noninvasive cardiac evaluation is of great importance in transgenic mice. Transthoracic echocardiography can visualize the left ventricle well but has not been as successful for the right ventricle (RV). We developed a method of transesophageal echocardiography (TEE) to evaluate murine RV size and function. METHODS AND RESULTS Normoxic and chronically hypoxic mice (F(IO2)=0.11, 3 weeks) and agarose RV casts were scanned with a rotating 3.5F/30-MHz intravascular ultrasound probe. In vivo, the probe was inserted in the mouse esophagus and withdrawn to obtain contiguous horizontal planes at 1-mm intervals. In vitro, the probe was withdrawn along the left ventricular posterior wall of excised hearts. The borders of the RV were traced on each plane, allowing calculation of diastolic and systolic volumes, RV mass, RV ejection fraction, stroke volume, and cardiac output. RV wall thickness was measured. Echo volumes obtained in vitro were compared with cast volumes. Echo-derived cardiac output was compared with measurements of an ascending aortic Doppler flow probe. Echo-derived RV free wall mass was compared with true RV free wall weight. There was excellent agreement between cast and TEE volumes (y=0.82x+6.03, r=0.88, P<0.01) and flow-probe and echo cardiac output (y=1.00x+0.45, r=0.99, P<0.0001). Although echo-derived RV mass and wall thickness were well correlated with true RV weight, echo-derived RV mass underestimated true weight (y=0.53x+2.29, r=0.81, P<0.0001). RV mass and wall thickness were greater in hypoxic mice than in normoxic mice (0.78+/-0.19 versus 0.51+/-0.14 mg/g, P<0.03, 0.50+/-0.03 versus 0.38+/-0.03 mm, P<0.04). CONCLUSIONS TEE with an intravascular ultrasound catheter is a simple, accurate, and reproducible method to study RV size and function in mice.

Reliability of Visual Assessment of Global and Segmental Left Ventricular Function: A Multicenter Study by the Israeli Echocardiography Research Group

BACKGROUND The purpose of this multicenter study was to determine the reliability of visual assessments of segmental wall motion (WM) abnormalities and global left ventricular function among highly experienced echocardiographers using contemporary echocardiographic technology in patients with a variety of cardiac conditions. METHODS The reliability of visual determinations of left ventricular WM and global function was calculated from assessments made by 12 experienced echocardiographers on 105 echocardiograms recorded using contemporary echocardiographic equipment. Ten studies were reread independently to determine intraobserver reliability. RESULTS Interobserver reliability for visual differentiation between normal, hypokinetic, and akinetic segments had an intraclass correlation coefficient of 0.70. The intraclass correlation coefficient for dichotomizing segments into normal versus other abnormal was 0.63, for hypokinetic versus other scores was 0.26, and for akinetic versus other scores was 0.58. Similar results were found for intraobserver reliability. Interobserver reliability for WM score index was 0.84 and for left ventricular ejection fraction was 0.78. Similar values were obtained for the intraobserver reliability of WM score index and ejection fraction. Compared to angiographic data, the accuracy of segmental WM assessments was 85%, and correct determination of the culprit artery was achieved in 59% of patients with myocardial infarctions. CONCLUSION Among experienced readers using contemporary echocardiographic equipment, interobserver and intraobserver reliability was reasonable for the visual quantification of normal and akinetic segments but poor for hypokinetic segments. Reliability was good for the visual assessment of global left ventricular function by WM score index and ejection fraction.

Briefly Trained Medical Students Can Effectively Identify Rheumatic Mitral Valve Injury Using a Hand-Carried Ultrasound

Rheumatic heart disease (RHD) is common and remains a major cause of morbidity, particularly in developing countries. Its diagnosis relies on expertise‐dependent echocardiographic studies. We evaluated the accuracy of briefly trained examiners in identifying RHD utilizing a hand‐carried cardiac ultrasound (HCU) device.

A new tool for automatic assessment of segmental wall motion based on longitudinal 2D strain: a multicenter study by the Israeli Echocardiography Research Group.

Background— Identification and quantification of segmental left ventricular wall motion abnormalities on echocardiograms is of paramount clinical importance but is still performed by a subjective visual method. We constructed an automatic tool for assessment of wall motion based on longitudinal strain. Methods and Results— Echocardiograms of 105 patients (3 apical views) were blindly analyzed by 12 experienced readers. Visual segmental scores (VSS) and peak systolic longitudinal strain were assigned to each of 18 segments per patient. Ranges of peak systolic longitudinal strain that best fit VSS (by receiver operating characteristic analysis) were used to generate automatic segmental scores (ASS). Comparisons of ASS and VSS were performed on 1952 analyzable segments. There was agreement of wall motion scores between both methods in 89.6% of normal, 39.5% of hypokinetic, and 69.4% of akinetic segments. Correlation between methods was r =0.63 ( P <0.0001). Interobserver and intraobserver reliability using interclass correlation for scoring segmental wall motion into 3 scores by ASS was 0.82 and 0.83 and by VSS 0.70 and 0.69, respectively. Compared with VSS (majority rule), ASS had a sensitivity, specificity, and accuracy of 87%, 85%, and 86%, respectively. ASS and VSS had similar success rates for correct identification of wall motion abnormalities in territories supplied by culprit arteries. VSS had greater specificity and positive predictive values, whereas ASS had higher sensitivity and negative predictive values for identifying the culprit artery. Conclusions— Automatic quantification of wall motion on echocardiograms by this tool performs as well as visual analysis by experienced echocardiographers, with a greater reliability and similar agreement to angiographic findings. Received December 16, 2008; accepted November 17, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Identification and quantification of segmental left ventricular wall motion abnormalities on echocardiograms is of paramount clinical importance but is still performed by a subjective visual method. We constructed an automatic tool for assessment of wall motion based on longitudinal strain. Methods and Results—Echocardiograms of 105 patients (3 apical views) were blindly analyzed by 12 experienced readers. Visual segmental scores (VSS) and peak systolic longitudinal strain were assigned to each of 18 segments per patient. Ranges of peak systolic longitudinal strain that best fit VSS (by receiver operating characteristic analysis) were used to generate automatic segmental scores (ASS). Comparisons of ASS and VSS were performed on 1952 analyzable segments. There was agreement of wall motion scores between both methods in 89.6% of normal, 39.5% of hypokinetic, and 69.4% of akinetic segments. Correlation between methods was r=0.63 (P<0.0001). Interobserver and intraobserver reliability using interclass correlation for scoring segmental wall motion into 3 scores by ASS was 0.82 and 0.83 and by VSS 0.70 and 0.69, respectively. Compared with VSS (majority rule), ASS had a sensitivity, specificity, and accuracy of 87%, 85%, and 86%, respectively. ASS and VSS had similar success rates for correct identification of wall motion abnormalities in territories supplied by culprit arteries. VSS had greater specificity and positive predictive values, whereas ASS had higher sensitivity and negative predictive values for identifying the culprit artery. Conclusions—Automatic quantification of wall motion on echocardiograms by this tool performs as well as visual analysis by experienced echocardiographers, with a greater reliability and similar agreement to angiographic findings.

Myocardial Perfusion and Wall Motion in Infarction Border Zone: Assessment by Myocardial Contrast Echocardiography

Several mechanisms have been proposed to explain the decreased wall motion (WM) at the borders of myocardial infarction (MI). We used myocardial contrast echocardiography (MCE) to investigate the relation of perfusion to WM in infarcted border zones (BZs) 6 weeks after MI in 5 sheep. After quantifying the extent of WM abnormality and the perfusion defect, normal (NL), infarcted, and BZs were defined. Peak intensity after contrast was measured in acoustic units (AU). Radiolabeled microspheres were injected to measure regional blood flow. The heart was stained with 2,3, 5-triphenyltetrazolium chloride (TTC). The perfusion defect on MCE was 33% +/- 7% of the total myocardial area and correlated well with TTC (r = 0.92, P <.03). The BZ was 8% +/- 5% of the total myocardial area. Peak intensity after contrast was decreased in MI compared with BZ and NL (MI: 2.5 +/- 1.9 AU, BZ: 8.0 +/- 3.8 AU, P <.005; NL: 10.2 +/- 6.9 AU, P <.02) and comparable in NL and BZ. The blood flow measured by microspheres was not different in NL and BZ but was decreased in MI (NL: 1.6 mL/g/min, BZ: 1.5 +/- 0.5 mL/g/min, MI: 0.7 +/- 0.5 mL/g/min; P <.0001). In this model of chronic ovine MI, the BZ was small and its perfusion was preserved. These findings support the hypothesis that tethering of normal myocardial segments explains the abnormal wall motion noted at the borders of MI.