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In this study, we sought evidence for an underlying atrial or ventricular myopathy in patients with paroxysmal lone atrial fibrillation using standard echocardiographic parameters in addition to Doppler tissue imaging of mitral annular motion. No impairment in atrial contractile function was found, but there was evidence for impaired diastolic function in these patients. [ABSTRACT FROM AUTHOR]

Background: Patients with non-ischemic heart failure etiology and left bundle branch block (LBBB) show better response to cardiac resynchronization therapy (CRT). While these patients have the most pronounced left ventricular (LV) dyssynchrony, LV dyssynchrony assessment often fails to predict outcome. We hypothesized that patients with favorable outcome from CRT can be identified by a characteristic strain distribution pattern., Methods: From 313 patients who underwent CRT between 2003 and 2006, we identified 10 patients who were CRT non-responders (no LV end-systolic volume [LVESV] reduction) with non-ischemic cardiomyopathy and LBBB and compared with randomly selected CRT responders (n = 10; LVESV reduction ≥15%). Longitudinal strain (εlong) data were obtained by speckle tracking echocardiography before and after (9 ± 5 months) CRT implantation and standardized segmental εlong-time curves were obtained by averaging individual patients., Results: In responders, ejection fraction (EF) increased from 25 ± 9 to 40 ± 11% (p = 0.002), while in non-responders, EF was unchanged (20 ± 8 to 21 ± 5%, p = 0.57). Global εlong was significantly lower in non-responders at pre CRT (p = 0.02) and only improved in responders (p = 0.04) after CRT. Pre CRT septal εlong -time curves in both groups showed early septal contraction with mid-systolic decrease, while lateral εlong showed early stretch followed by vigorous mid to late contraction. Restoration of contraction synchrony was observed in both groups, though non-responder remained low amplitude of εlong., Conclusions: CRT non-responders with LBBB and non-ischemic etiology showed a similar improvement of εlong pattern with responders after CRT implantation, while amplitude of εlong remained unchanged. Lower εlong in the non-responders may account for their poor response to CRT.

Background: In patients with hypertrophic cardiomyopathy and left ventricular outflow tract (LVOT) obstruction, but without basal septal hypertrophy, we sought to identify mitral valve (MV) and papillary muscle (PM) abnormalities that predisposed to LVOT obstruction, using echo and cardiac magnetic resonance., Methods and Results: We studied 121 patients with hypertrophic cardiomyopathy hypertrophic cardiomyopathy (age, 49±17 years; 60% men; 57% on β-blockers) with a basal septal thickness of ≤1.8 cm who underwent echocardiography (rest+stress) and cine cardiac magnetic resonance. Echo measurements included maximal LVOT gradient (rest/provocable), MV leaflet length (parasternal long, 4 and 3-chamber views), and abnormal chordal attachment to mid/base of anterior MV. Cine cardiac magnetic resonance measurements included basal septal thickness, number/area of PM heads, and bifid PM mobility (in systole and diastole). Mean basal septal thickness, LVOT gradient, and LV ejection fraction were 1.5±0.3 cm, 72±54 mm Hg, and 61±6%, respectively. The number of anterolateral and posteromedial PM heads was 2.7±0.7 and 2.6±0.7, respectively. Anterolateral and posteromedial PM areas were 19.9±7 cm(2) and 17.1±6 cm(2), respectively. PM mobility was 11±6°. On multivariable analysis, predictors of maximal LVOT gradient were basal septal thickness, bifid PM mobility, anterior mitral leaflet length, and abnormal chordal attachment to base of anterior mitral leaflet. Forty-five patients underwent surgery to relieve LVOT obstruction, of which 52% needed an additional nonmyectomy (MV repair/replacement or PM reorientation) approach., Conclusions: In hypertrophic cardiomyopathy patients without significant LV hypertrophy, in addition to basal septal thickness, anterior MV length, abnormal chordal attachment, and bifid PM mobility are associated with LVOT obstruction. In such patients, additional procedures on MV and PM (±myectomy) could be considered., (© 2015 American Heart Association, Inc.)

Background: Longitudinal strain (LS) imaging is an important tool for the quantification of left ventricular function and deformation, but its assessment is challenging in the presence of echocardiographic contrast agents (CAs). The aim of this study was to test the hypothesis that destruction of microbubbles using high mechanical index (MI) could allow the measurement of LS., Methods: LS was measured using speckle strain (speckle-tracking LS [STLS]) and Velocity Vector Imaging (VVI) before and after CA administration in 30 consecutive patients. Low MI was used for left ventricular opacification and three-dimensional high MI for microbubble destruction. Four different settings were tested over 60 sec: (1) baseline LS without contrast, (2) LS after CA administration with low MI (0.3), (3) LS after CA administration with high MI (0.9), and (4) LS after microbubble destruction with high MI and three-dimensional imaging., Results: Baseline feasibility of LS assessment (99.3% and 98.2% with STLS and VVI, respectively) was reduced after CA administration using STLS at low (69%, P < .0001) and high (95.4%, P = .0002) MI as well as with VVI (93.8%, P = .004, and 84.7%, P < .0001, respectively). STLS assessment was feasible with high MI after microbubble destruction (1.7% of uninterpretable segments vs 0.7%, P = .26) but not using VVI (7.2% vs 1.8%, P < .001). Regardless of which microbubbles or image settings were used, VVI was associated with significant variability and overestimation of global LS (for low MI, +4.7%, P < .01; for high MI, +3.3%, P < .001; for high MI after microbubble destruction, +1.3%, P = .04)., Conclusions: LS assessment is most feasible without contrast. If a CA is necessary, the calculation of LS is feasible using the speckle-tracking method, if three-dimensional imaging is used as a tool for microbubble destruction 1 min after CA administration., (Copyright © 2012. Published by Mosby, Inc.)

Background: Although atrial ventricular (AV) intervals are often optimized at rest in patients receiving cardiac resynchronization therapy (CRT), there are limited data on the impact of exercise on optimal AV interval., Methods: In 15 patients with CRT, AV intervals were serially programmed while patients were supine and at rest, and during exercise with heart rates that averaged 20 and 40 beats per minute above their resting rates. Echocardiographic Doppler images were acquired at each programmed AV interval and each rate. Three independent echocardiographic criteria were retrospectively used to determine each patient's optimal AV interval as a function of exercise-induced increased heart rates: the duration of left ventricular filling, stroke volume, and a clinical assessment of left ventricular function., Results: A negative correlation between the optimal AV interval and heart rate was observed across all patients using all three independent criterion: the maximum left ventricular filling time (slope =-0.77, intercept = 151.9, r = 0.55, P < 0.001), maximum stroke volume (slope =-0.93, intercept = 183.3, r = 0.50, P = 0.002), or the subjective clinical assessment (slope =-1.06, intercept = 182.0, r = 0.72, P < 0.001). Consistent trends were observed between all three parameters for 12 out of the 15 patients., Conclusions: These results suggest that in patients indicated for CRT, rate-adaptive functions may be useful to shorten AV intervals with increased rate, in order to maximize left ventricular filling, stroke volume, and clinical left ventricular function. Further studies are necessary to determine the clinical impact of these rate-adaptive algorithms.

Objectives: This study sought to assess whether longitudinal rotation (LR) affects myocardial systolic velocity profiles and to compare velocity-based measures of dyssynchrony with LR for predicting cardiac resynchronization therapy (CRT) response., Background: Longitudinal rotation, a rocking motion often seen when the dilated left ventricle (LV) is imaged in its horizontal long-axis plane, is a recently recognized phenomenon and a new predictor of response to CRT., Methods: One hundred patients with CRT implants and suitable baseline echocardiograms were identified. Longitudinal rotation was assessed in the apical 4-chamber view by speckle-tracking techniques and myocardial systolic velocities for basal septum, and lateral LV were analyzed from tissue Doppler images. The quartiles of LR distribution were analyzed for differences in their systolic velocities. Correlation between measurements and reduction in LV end-systolic volume (ESV) at follow-up was performed., Results: Quartile 1 had a mean LR of -6.8 +/- 2.3 degrees ; quartile 4 showed a mean LR of 2.3 +/- 1.6 degrees . A depressed peak velocity of lateral wall, when compared with the septum, was found for quartile 1 (p = 0.01), whereas the converse was noted in quartile 4 (p = 0.0001). The difference in amplitude of peak velocity between septal and lateral walls was found to correlate with the pattern of LR and with percentage reduction in LV ESV at follow-up in nonischemic patients. Septal-lateral delay was not correlated with the presence of LR, nor was it predictive of reduction in LV ESV., Conclusions: Patients with prominent clockwise LR have depressed long-axis systolic velocities of the lateral wall, whereas the patients with counterclockwise LR have depressed septal wall velocities. The difference in peak amplitude of basal septal and lateral systolic velocities is predictive of LR, and in the nonischemic subgroup correlates with quantitative LV reverse remodeling at follow-up. Velocity time-based measures, including septal-lateral delay were not predictive of CRT response.

The optimal pacing site in cardiac resynchronization therapy (CRT) remains controversial. Tissue synchronization imaging is a novel echocardiographic technique that color-codes for areas of maximal delay in myocardial velocities. This study aimed to identify whether the left ventricular (LV) pacing lead position in CRT should be guided by a patient's area of maximal mechanical delay. Fifty-four patients with advanced heart failure were assessed echocardiographically before and 6 months after CRT. Response was analyzed according to the relation between the LV lead position and the area of maximal delay to peak velocity by tissue synchronization imaging in the first half of the ejection phase: group 1 (n = 22) had lead placement corresponding to the segment of maximal delay; group 2 (n = 13) had lead placement 1 segment adjacent; and group 3 (n = 19) had lead placement remote from this site. Evidence of LV reverse remodeling and improved systolic function was documented in group 1 (mean percentage decrease in end-systolic volume 23%) more than in group 2 (mean decrease 15%), and more than in group 3 (mean increase 8.9%, p <0.0001 compared with groups 1 and 2). In group 1, 16 of 22 patients had reverse remodeling (>15% decrease in end-systolic volume); reverse remodeling was seen in 7 of 13 patients in group 2 and 1 of 19 in group 3. The placing of the lead position proximal to the site of maximal delay by tissue synchronization imaging was correlated with reverse remodeling (r = 0.449, p = 001). Of 7 patients with delay confined to the septum and anterior wall only, none had evidence of reverse remodeling after CRT. In conclusion, pacing at the site of maximal mechanical delay was associated with reverse remodeling. Individually tailored LV lead positioning should be considered before CRT.

Background: Annular geometry and motion in functional ischemic mitral regurgitation are incompletely understood. Three-dimensional echocardiography demonstrates saddle-shaped annular geometry, but standard methodology does not enable quantification of annular motion. Therefore, a novel technique using three-dimensional echocardiography and computer software was used to characterize alterations in mitral annular geometry and motion in patients with ischemic mitral regurgitation., Methods: We developed a computer program to reconstruct the mitral annulus based on spatial coordinates from three-dimensional echocardiography. Data were obtained at end-diastole and end-systole in 7 patients with ischemic mitral regurgitation and 5 normal control subjects. Mitral annular motion was quantified by calculating the displacement area of the annulus between end-diastole and end-systole., Results: Comparison of ischemic mitral regurgitation and control patients revealed differences in annular geometry and motion at end-diastole. Annular perimeter was greater in ischemic mitral regurgitation patients (10.7 +/- 0.7 cm versus 8.6 +/- 0.2 cm in control group; p < 0.03), with increased intertrigonal distance in ischemic mitral regurgitation patients (2.8 +/- 0.3 cm versus 2.1 +/- 0.1 cm; p < 0.06). These changes resulted in increased annular orifice area in ischemic mitral regurgitation patients (9.1 +/- 1.2 cm2 versus 5.7 +/- 0.3 cm2; p < 0.03). Ischemic mitral regurgitation patients had altered annular motion, with reduced movement of the posterior annulus (5.4 +/- 0.7 cm2 versus 8.7 +/- 1.1 cm2; p < 0.03)., Conclusions: Computer analysis of data obtained from three-dimensional echocardiography demonstrates altered annular geometry and motion in patients with ischemic mitral regurgitation. Patients with ischemic mitral regurgitation have annular dilatation, with an increase in anterior and posterior annular perimeters; this is accompanied by an increase in the intertrigonal distance and restriction of annular motion.

Objectives: To evaluate the pharmacodynamic effects of an experimental (EXP) delivery of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder and to investigate the situational nature of effects in laboratory classroom and playground settings., Method: A "sipping" study methodology was used to deliver a bolus followed by small but increasing MPH doses as the EXP regimen. A randomized, double-blind crossover design was used to compare the EXP regimen to a thrice-daily (TID) regimen and a placebo (PLA) regimen. Measures of efficacy were obtained from a Motionlogger actigraph to quantify activity and from the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale to quantify two domains of behavior (attention and deportment)., Results: Compared with PLA, both EXP and TID delivery of MPH produced large, significant reductions in activity and inappropriate behavior in the classroom, but the two MPH regimens did not differ in onset or duration of effects across the day. The MPH effects were situationally dependent and were smaller for the playground than for the classroom settings., Conclusions: The findings of this "proof of concept" study support the efficacy of a continuous, ascending delivery of MPH. The situational effects of MPH provide support for the theory of selective effects of stimulants, dependent on the demands of the environment.

The clinical assessment of left ventricular (LV) systolic function during atrial fibrillation (AF) is unreliable and difficult because of beat-to-beat variability. We evaluated an index for the estimation of LV systolic function in AF that is based on the relationship between the preceding (R-R1) and prepreceding (R-R2) R-R intervals. LV Doppler stroke volume (SV), ejection fraction (EF), peak aortic flow rate (AoF) and the maximum value of the first derivative of the LV pressure curve (dP/dt(max)) were evaluated in 13 healthy open-chest dogs during triggered AF. All parameters showed a significantly strong positive linear relationship with the ratio of R-R1/R-R2 (r = 0.65, 0.74, 0.75, and 0.70 for SV, EF, AoF, and dP/dt(max), respectively). The calculated value of LV systolic parameters at R-R1/R-R2 = 1 in the linear regression line showed a good relationship and an agreement with the measured average value of the parameter over all cardiac cycles (SV, 12.1 vs. 12.8 ml; EF, 49.6 vs. 51.2%; AoF, 1.37 vs. 1.48 l/min; and dP/dt(max), 2,323 vs. 2,454 mmHg/s). Using the LV systolic parameters estimated at R-R1/R-R2 = 1 in the linear regression line allows the LV contractile function to be accurately and reproducibly evaluated during AF and obviates the less-reliable process of averaging multiple cardiac cycles.

Objectives: To evaluate the efficacy of several drug delivery patterns of methylphenidate and to determine whether acute tolerance develops to this widely used stimulant medication in the treatment of children with attention deficit hyperactivity disorder., Methods: Double-blind trials were conducted in a laboratory school setting in which multiple measures of efficacy were obtained frequently in the morning and afternoon across the school day. In study I, relative efficacy was determined for three dosing patterns of methylphenidate: a standard twice-daily profile, a flat profile, and an ascending profile. In study II, tolerance was assessed by comparison of three-times-a-day regimens in which the time of the middle dose varied., Results: In study I, the efficacy of the ascending treatment increased across the day, and in the afternoon it was equal to the efficacy of the twice-daily treatment, indicating that an initial bolus was not required for efficacy. The efficacy of the flat treatment declined across the day, and in the afternoon it was significantly less than in the twice-daily treatment, suggesting that tolerance may be developing. In study II, acute improvements in efficacy were reduced to the second of two closely spaced but not to two widely spaced bolus doses, suggesting that shortly after exposure to high concentrations, efficacy is reduced to given concentrations of methylphenidate. In a concentration-effect model, a tolerance term was needed to account for counterclockwise hysteresis., Conclusions: Acute tolerance to methylphenidate appears to exist. This should be considered in the design of an optimal dosing regimen for the treatment of children with attention deficit hyperactivity disorder.

Objective: This was a randomized, double-blind, crossover study of 30 children with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive control (placebo), and a positive control (clinical dose of methylphenidate)., Method: For each treatment condition, a capsule was administered in the morning and assessments were performed in an analog classroom setting every 1.5 hours across the day. Subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measures were obtained for each classroom session, and these measures were used to evaluate time-response and dose response effects of Adderall., Results: For doses of Adderall greater than 5 mg, significant time course effects were observed. Rapid improvements on teacher ratings and math performance were observed by 1.5 hours after administration, and these effects dissipated by the end of the day. The specific pattern of time course effects depended on dose: the time of peak effects and the duration of action increased with dose of Adderall., Conclusions: This documentation of efficacy in a controlled study supports the addition of Adderall to the armamentarium of psychotropic medications for the treatment of ADHD. The differences in time-response patterns of Adderall and methylphenidate may help tailor treatment to meet specific clinical needs of different children with ADHD.

In this article, we describe graphical and statistical methods developed to evaluate the response patterns of individual children with attention deficit hyperactivity disorder (ADHD) to different conditions of treatment with stimulant medication. We used data from an investigation of drug delivery patterns to demonstrate these methods. Thirty-one children with ADHD participated in a double-blind crossover study of four conditions (three patterns of delivery of methylphenidate and a placebo control). In each condition, the children were evaluated across an 11-hour (7:00 a.m. to 6:00 p.m.) laboratory school day, and ratings of classroom behavior were obtained at regular intervals across the day. Graphical procedures were developed to display, for each individual, time courses of multiple measures of behavior taken across each double-blind test day. Expert clinicians judged these graphs and used this information to rank-order the test days from best to worst. A within-subject variant of Kendall's W was used to evaluate, for each subject, whether the rankings of these multidimensional graphs were reliable (concordant) across judges. A generalized kappa statistic was used to evaluate, for each condition, the reliability of the judges' rankings across subjects. Friedman's analysis of variance of ranks was used to evaluate, for the study, whether the conditions differed in terms of the average (consensus) rank assigned by the judges.

In a randomized double-blind crossover study of children with attention deficit hyperactivity disorder (ADHD), the time course effects of four doses of Adderall (5, 10, 15, and 20 mg) and an inactive (placebo) control, and an active (Ritalin) control were evaluated. A laboratory classroom setting was established in which subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measurements were taken every 1.5 hours across the day. In addition to significant time and dose effects of Adderall, significant time-of-day effects were documented in the placebo condition for the subjective measure of deportment and objective measures of performance. Regression analyses were used to estimate the magnitude of these baseline effects. Correlations across time were used to evaluate the test-retest reliability of each measure in the face of these time-dependent placebo effects. After placebo/time adjustments, within-subject correlations between pairs of measures were used to evaluate the validity of the math test as a measure of response to stimulant medication.

Objectives: This study was designed to assess the accuracy of two-dimensional and Doppler echocardiography in determining the mechanism of mitral regurgitation, as compared with direct inspection of the valve at operation., Background: Valve repair for mitral regurgitation offers substantial advantages over valve replacement, but it is technically more demanding and requires understanding of the mechanism of dysfunction., Methods: We studied 286 patients undergoing mitral valve repair. Intraoperative two-dimensional echocardiography was used to classify mitral leaflet motion as excessive, normal or restricted. Doppler color flow mapping was used to evaluate the direction and origin of the mitral regurgitant jet. Two-dimensional and Doppler echocardiography were compared with intraoperative surgical determination of the mechanism of dysfunction, which also classified leaflet motion as excessive, normal or restricted., Results: Two-dimensional and Doppler echocardiography accurately diagnosed the mechanism of mitral regurgitation in 123 (93%) of 132 patients with posterior leaflet prolapse or flail, 30 (94%) of 32 patients with anterior leaflet prolapse or flail, 11 (44%) of 25 patients with bileaflet prolapse or flail, 6 (75%) of 8 patients with papillary muscle elongation or rupture, 31 (91%) of 34 patients with restricted leaflet motion or rheumatic thickening, 21 (72%) of 29 patients with ventricular-annular dilation and 8 (62%) of 13 patients with a leaflet perforation or cleft. Of 13 patients with two mechanisms of dysfunction by surgical inspection, two-dimensional and Doppler echocardiography correctly diagnosed one of the two mechanisms in 12 patients (92%), and both mechanisms in 5 patients (38%). Overall, echocardiographic determination of leaflet motion and Doppler determination of jet direction accurately diagnosed the mechanism of dysfunction in 242 (85%) of 286 patients., Conclusions: Echocardiography before mitral valvuloplasty provides a dynamic appraisal of the mechanism of dysfunction, enabling the surgeon to systematically understand the dysfunction and successfully apply the correct procedures to eliminate mitral regurgitation without valve replacement.