Neil L. Greenberg

Enhanced Ventricular Untwisting During Exercise A Mechanistic Manifestation of Elastic Recoil Described by Doppler Tissue Imaging

Background— The cascade of events by which early diastolic left ventricular (LV) filling increases with exercise is not fully elucidated. Doppler tissue imaging (DTI) can detect myocardial motion, including torsion, whereas color M-mode Doppler (CMM) can quantify LV intraventricular pressure gradients (IVPGs). Methods and Results— Twenty healthy volunteers underwent echocardiographic examination with DTI at rest and during submaximal supine bicycle exercise. We assessed LV long-/short-axis function, torsion, volume, inflow dynamics, and early diastolic IVPG derived from CMM data. LV torsion and untwisting velocity increased with exercise (torsion, 11±4° to 24±8°; untwisting velocity, −2.0±0.7 to −5.6±2.3 rad/s) that was associated with an increase in IVPG (1.4±0.5 to 3.7±1.2 mm Hg). Untwisting in normal subjects occurred during isovolumic relaxation and early filling, significantly before long-axis lengthening or radial expansion. The clinical feasibility of this method was tested in 7 patients with hypertrophic cardiomyopathy (HCM); torsion was higher at rest but did not increase with exercise (16±4° to 14±6°), whereas untwisting was delayed and unenhanced (−1.6±0.8 to −2.3±1.2 rad/s). In concert, IVPG was similar at rest (1.2±0.3 mm Hg), but the exercise response was blunted (1.6±0.8 mm Hg). In normal subjects and HCM patients, there was a similar linear relation between IVPG and untwisting rate, with an overall correlation coefficient of r=0.75 (P<0.0001). Conclusions— LV untwisting appears to be linked temporally with early diastolic base-to-apex pressure gradients, enhanced by exercise, which may assist efficient LV filling, an effect that appears blunted in HCM. Thus, LV torsion and subsequent rapid untwisting appear to be manifestations of elastic recoil, critically linking systolic contraction to diastolic filling.

Assessment of left ventricular torsional deformation by Doppler tissue imaging: Validation study with tagged magnetic resonance imaging

Background—Left ventricular (LV) torsional deformation is a sensitive index for LV performance but difficult to measure. The present study tested the accuracy of a novel method that uses Doppler tissue imaging (DTI) for quantifying LV torsion in humans with tagged magnetic resonance imaging (MRI) as a reference. Methods and Results—Twenty patients underwent DTI and tagged MRI studies. Images of the LV were acquired at apical and basal short-axis levels to assess LV torsion. We calculated LV rotation by integrating the rotational velocity, determined from DTI velocities of the septal and lateral regions, and correcting for the LV radius over time. LV torsion was defined as the difference in LV rotation between the 2 levels. DTI rotational and torsional profiles throughout systole and diastole were compared with those by tagged MRI at isochronal points. Rotation and torsion by DTI were closely correlated with tagged MRI results during systole and early diastole (apical and basal rotation, r=0.87 and 0.90, respectively; for torsion, 0.84; P<0.0001, by repeated-measures regression models). Maximal torsion showed even better correlation (r=0.95, P<0.0001). Conclusions—The present study has shown that DTI can quantify LV torsional deformation over time. This novel method may facilitate noninvasive quantification of LV torsion in clinical and research settings.

Left Atrial Strain Measured by Two-Dimensional Speckle Tracking Represents a New Tool to Evaluate Left Atrial Function

BACKGROUND Left atrial (LA) strain (epsilon) and epsilon rate (SR) analysis by two-dimensional speckle tracking can represent a new tool to evaluate LA function. To assess its potential value, the authors addressed whether LA epsilon and SR measured in normal subjects correlates with other Doppler echocardiographic parameters that evaluate LA function and left ventricular function. METHODS Sixty-four healthy subjects were studied. LA epsilon and SR were calculated with the reference point set at the P wave, which enabled the recognition of peak negative epsilon (epsilon(neg peak)), peak positive epsilon (epsilon(pos peak)), and the sum of those values, total LA epsilon (epsilon(tot)), corresponding to LA contractile, conduit, and reservoir function, respectively. Similarly, peak negative SR (LA SR(late neg peak)) during LA contraction, peak positive SR (LA SR(pos peak)) at the beginning of LV systole, and peak negative SR (LA SR(early neg peak)) at the beginning of LV diastole were identified. RESULTS Global LA epsilon(pos peak), epsilon(neg peak), and epsilon(tot) were 23.2 +/- 6.7%, -14.6 +/- 3.5%, and 37.9 +/- 7.6%, respectively. Global LA SR(pos peak), SR(early neg peak) , and SR(late neg peak) were 2.0 +/- 0.6 s(-1), -2.0 +/- 0.6 s(-1), and -2.3 +/- 0.5 s(-1), respectively. The above-described variables derived from analysis of global LA epsilon and LA SR correlated significantly with Doppler echocardiographic indexes that evaluated the same phase of the cardiac cycle or the same component of the LA function, including indexes derived from mitral inflow, pulmonary vein velocities, tissue Doppler, and LA volumes. Global LA epsilon(pos peak), LA epsilon(tot), and LA SR(early neg peak) also correlated significantly with age or body mass index. Global LA SR(late neg peak) also correlated significantly with age. CONCLUSIONS LA epsilon analysis is a new tool that can be used to evaluate LA function. Further studies are warranted to determine the utility of LA epsilon in disease states.

Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery.

OBJECTIVES This study was conducted to evaluate follow-up results in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent either percutaneous transluminal septal myocardial ablation (PTSMA) or septal myectomy. BACKGROUND Controversy exists with regard to these two forms of treatment for patients with HOCM. METHODS Of 51 patients with HOCM treated, 25 were treated by PTSMA and 26 patients via myectomy. Two-dimensional echocardiograms were performed before both procedures, immediately afterwards and at a three-month follow-up. The New York Heart Association (NYHA) functional class was obtained before the procedures and at follow-up. RESULTS Interventricular septal thickness was significantly reduced at follow-up in both groups (2.3 +/- 0.4 cm vs. 1.9 +/- 0.4 cm for septal ablation and 2.4 +/- 0.6 cm vs. 1.7 +/- 0.2 cm for myectomy, both p < 0.001). Estimated by continuous-wave Doppler, the resting pressure gradient (PG) across the left ventricular outflow tract (LVOT) significantly decreased immediately after the procedures in both groups (64 +/- 39 mm Hg vs. 28 +/- 29 mm Hg for PTSMA, 62 +/- 43 mm Hg vs. 7 +/- 7 mm Hg for myectomy, both p < 0.0001). At three-month follow-up, the resting PG remained lower in the PTSMA and myectomy groups (24 +/- 19 mm Hg and 11 +/- 6 mm Hg, respectively, vs. those before procedures, both p < 0.0001). The NYHA functional class was also significantly improved in both groups (3.5 +/- 0.5 vs. 1.9 +/- 0.7 for PTSMA, 3.3 +/- 0.5 vs. 1.5 +/- 0.7 for myectomy, both p < 0.0001). CONCLUSIONS Both myectomy and PTSMA reduce LVOT obstruction and significantly improve NYHA functional class in patients with HOCM. However, there are benefits and drawbacks for each therapeutic method that must be counterbalanced when deciding on treatment for LVOT obstruction.

Three-Dimensional Geometry of the Tricuspid Annulus in Healthy Subjects and in Patients With Functional Tricuspid Regurgitation A Real-Time, 3-Dimensional Echocardiographic Study

Background— Most rings currently used for tricuspid valve annuloplasty are formed in a single plane, whereas the actual tricuspid annulus (TA) may have a nonplanar or 3-dimensional (3D) structure. The purpose of this study was therefore to investigate the 3D geometry of the TA in healthy subjects and in patients with functional tricuspid regurgitation (TR). Methods and Results— This study consisted of 15 healthy subjects and 16 patients with functional TR who had real-time 3D echocardiography. With our customized software, 8 points along the TA were determined with the rotated plane around the axis at 45°intervals. The TA was traced during a cardiac cycle. The distance between diagonals connecting 2 points was measured. The height was defined as the distance from the plane determined by least-squares regression analysis at all 8 points. Both the maximum (7.5±2.1 versus 5.6±1.0 cm2/m2) and minimum (5.7±1.3 versus 3.9±0.8 cm2/m2) TA areas in patients with TR were larger than those in healthy subjects (both P<0.01). Healthy subjects had a nonplanar-shaped TA with homogeneous contraction. The posteroseptal portion was the lowest toward the apex from the right atrium, and the anteroseptal portion was the highest. In patients with functional TR, the TA was dilated in the septal to lateral direction, resulting in a more circular shape than in healthy subjects. A similar 3D pattern was observed in patients with TR, but it was more planar than that in healthy subjects. Conclusions— Real-time 3D echocardiography showed a complicated 3D structure of the TA, which appeared to be different from the “saddle-shaped” mitral annulus, suggesting an annuloplasty for TR different from that for mitral regurgitation.

Association Between Regional Ventricular Function and Myocardial Fibrosis in Hypertrophic Cardiomyopathy Assessed by Speckle Tracking Echocardiography and Delayed Hyperenhancement Magnetic Resonance Imaging

The relationship among myocardial fibrosis, segmental strains, and hypertrophic cardiomyopathy (HCM) in patients with preserved left ventricular ejection fraction is not known. We evaluated this relationship in 39 consecutive patients with HCM with transthoracic echocardiography and delayed hyperenhancement magnetic resonance imaging 20 minutes after injection of 0.2 mmol/kg of gadolinium. Speckle tracking echocardiography was used to assess left ventricle strains. Fibrosis was determined semiautomatically with magnetic resonance imaging, using a 12-segment short-axis left ventricular model. Myocardial fibrosis was detected in 23 of 39 patients with HCM. The mean end-systolic longitudinal strain correlated with the number of fibrotic segments (r = 0.47, P =.002) and total myocardial fibrosis (r = 0.46, P =.003). Fibrosis and wall thickness were both multivariate predictors of lower segmental longitudinal strain (P <.003). Longitudinal, circumferential, and radial strains are decreased in patients with HCM even in the absence of fibrosis. Myocardial fibrosis is associated with depressed longitudinal strain in patients with HCM.

Longitudinal Strain Delay Index by Speckle Tracking Imaging A New Marker of Response to Cardiac Resynchronization Therapy

Background— In heart failure patients with left ventricular dyssynchrony, contractility in delayed segments does not fully contribute to end-systolic function. We quantified this reserve of contraction related to mechanical dyssynchrony to predict response to cardiac resynchronization therapy by the strain delay index, which was defined as the sum of the difference between peak and end-systolic strain across 16 segments. Methods and Results— In 100 heart failure patients (ejection fraction=26±9%, QRS=154±29 ms, 94% in New York Heart Association class III), we studied left ventricular dyssynchrony before cardiac resynchronization therapy by the strain delay index using longitudinal strain by 2D speckle tracking and by the SD of time to peak myocardial velocity in 12 segments. The optimal cutoff value of the strain delay index to predict response to cardiac resynchronization therapy was determined in a retrospective group (n=65) and then confirmed in a validation group (n=35). Left ventricular end-systolic volume reduction at 3 months >15% (responder) occurred in 64 of 100 patients. In the retrospective group, the strain delay index but not the SD of time to peak myocardial velocity was greater in responders (n=42/65) than nonresponders (35±8% versus 19±7%, P<0.0001), and the optimal cutoff value to identify response to cardiac resynchronization therapy was 25%. In the validation group, strain delay index ≥25% identified 82% (18/22) of responders and 92% (12/13) of nonresponders. Among the entire population (n=100), strain delay index correlated with reverse remodeling in both the ischemic (r=−0.68, P<0.0001) and nonischemic (r=−0.68, P<0.0001) population. Conclusions— Use of the strain delay index with longitudinal strain by speckle tracking has a strong predictive value for predicting response to cardiac resynchronization therapy in both ischemic and nonischemic patients.

Maturational and Adaptive Modulation of Left Ventricular Torsional Biomechanics. Doppler Tissue Imaging Observation From Infancy to Adulthood

Background— Left ventricular (LV) torsional deformation, based in part on the helical myocardial fiber architecture, is an important component of LV systolic and diastolic performance. However, there is no comprehensive study describing its normal development during childhood and adult life. Methods and Results— Forty-five normal subjects (25 children and 20 adults; aged 9 days to 49 years; divided into 5 groups: infants, children, adolescents, and young and middle-age adults) underwent assessment of LV torsion and untwisting rate by Doppler tissue imaging. LV torsion increased with age, primarily owing to augmentation in basal clockwise rotation during childhood and apical counterclockwise rotation during adulthood. Although LV torsion and untwisting overall showed age-related increases, when normalized by LV length, they showed higher values in infancy and middle age. The proportion of untwisting during isovolumic relaxation was lowest in infancy, increased during childhood, and leveled off thereafter, whereas peak untwisting performance (peak untwisting velocity normalized by peak LV torsion) showed a decrease during adulthood. Conclusions— We have shown the maturational process of LV torsion in normal subjects. Net LV torsion increases gradually from infancy to adulthood, but the determinants of this were different in the 2 age groups. The smaller LV isovolumic untwisting recoil during infancy and its decline in adulthood may suggest mechanisms for alterations in diastolic function.

Validation of real-time three-dimensional echocardiography for quantifying left ventricular volumes in the presence of a left ventricular aneurysm: in vitro and in vivo studies

OBJECTIVES To validate the accuracy of real-time three-dimensional echocardiography (RT3DE) for quantifying aneurysmal left ventricular (LV) volumes. BACKGROUND Conventional two-dimensional echocardiography (2DE) has limitations when applied for quantification of LV volumes in patients with LV aneurysms. METHODS Seven aneurysmal balloons, 15 sheep (5 with chronic LV aneurysms and 10 without LV aneurysms) during 60 different hemodynamic conditions and 29 patients (13 with chronic LV aneurysms and 16 with normal LV) underwent RT3DE and 2DE. Electromagnetic flow meters and magnetic resonance imaging (MRI) served as reference standards in the animals and in the patients, respectively. Rotated apical six-plane method with multiplanar Simpsons rule and apical biplane Simpsons rule were used to determine LV volumes by RT3DE and 2DE, respectively. RESULTS Both RT3DE and 2DE correlated well with actual volumes for aneurysmal balloons. However, a significantly smaller mean difference (MD) was found between RT3DE and actual volumes (-7 ml for RT3DE vs. 22 ml for 2DE, p = 0.0002). Excellent correlation and agreement between RT3DE and electromagnetic flow meters for LV stroke volumes for animals with aneurysms were observed, while 2DE showed lesser correlation and agreement (r = 0.97, MD = -1.0 ml vs. r = 0.76, MD = 4.4 ml). In patients with LV aneurysms, better correlation and agreement between RT3DE and MRI for LV volumes were obtained (r = 0.99, MD = -28 ml) than between 2DE and MRI (r = 0.91, MD = -49 ml). CONCLUSIONS For geometrically asymmetric LVs associated with ventricular aneurysms, RT3DE can accurately quantify LV volumes.

Geometry of the proximal isovelocity surface area in mitral regurgitation by 3-dimensional color Doppler echocardiography: Difference between functional mitral regurgitation and prolapse regurgitation

BACKGROUND The geometry of the proximal isovelocity surface area (PISA) of functional mitral regurgitation (MR), which is conventionally assumed to be a hemisphere, remains to be clarified. We investigated the 3-dimensional (3D) geometry of PISA of functional MR as opposed to that of MR due to mitral valve prolapse (MVP) by real-time 3D echocardiography with color Doppler capability. METHODS Twenty-seven patients with functional MR and 27 patients with MVP were examined. The horizontal PISA length in the commissure-commissure plane and each PISA radius in 3 anteroposterior planes (medial, central, and lateral) were measured by real-time 3D echocardiography with 3D software. The effective regurgitant orifice (ERO) area was calculated with the maximum PISA radius and compared to that by 2D quantitative Doppler method. RESULTS En-face 3D color Doppler images showed an elongated and slightly curved PISA geometry along the leaflet coaptation in functional MR, whereas the geometry was rounder in MVP. The PISA horizontal length in functional MR was longer than that in MVP (2.3 +/- 0.4 vs 1.2 +/- 0.2 cm, P < .001). The PISA method with the maximum radius underestimated the ERO area by 2D quantitative Doppler method (by 24%) in functional MR, but not in MVP. CONCLUSIONS The geometry of PISA in functional MR was elongated, distinctly different from the more focal pathology of MVP, leading to underestimation of the ERO area by PISA method.