Longitudinal rotation: an unrecognised motion pattern in patients with dilated cardiomyopathy.

BACKGROUND: Heart failure patients who are candidates for CRT frequently display longitudinal rotation (LR) - a swinging motion of the heart when imaged in a horizontal long-axis plane. OBJECTIVES: To identify the magnitude and predictors of LR in patients with ischaemic (ICM) and idiopathic dilated (DCM) cardiomyopathy, and to assess predictive value of LR in patients undergoing cardiac resynchronisation therapy (CRT). DESIGN AND SETTING: A retrospective study in a tertiary heart care setting. METHODS: Echocardiography was performed in 45 ICM and 41 DCM patients who were CRT candidates and 16 control subjects. Global LR, segmental strains and segmental LR were assessed from echocardiograms using speckle tracking. Repeat echocardiography >40 days after the beginning of CRT was performed in 64 patients. RESULTS: While DCM patients with QRS duration of both <130 ms and > or =130 ms displayed significant clockwise LR (p<0.001 for both vs 0), ICM patients and control subjects had LR that did not differ from 0. The most significant LR predictor was end-diastolic volume (p<0.001) followed by the absence of ischaemia (p<0.001) and QRS duration (p = 0.05). DCM patients with prominent clockwise LR had lower septal but higher lateral strains than DCM patients with minimal LR, or ICM patients with counterclockwise LR. LR correlated with decrease of end-systolic volume in DCM (r = 0.49, p = 0.004), while no relationship was observed in ICM. CONCLUSION: Clockwise LR is linked to presence of DCM, with the small impact of QRS duration. LR is a moderately strong predictor of end-systolic volume decrease during CRT in DCM.

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.

Assessment of LV systolic function in atrial fibrillation using an index of preceding cardiac cycles.

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.

Left ventricular diastolic dysfunction in lone atrial fibrillation determined by Doppler tissue imaging of mitral annular motion.

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.

Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children.

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.

New echocardiographic windows for quantitative determination of aortic regurgitation volume using color Doppler flow convergence and vena contracta.

Color Doppler images of aortic regurgitation (AR) flow acceleration, flow convergence (FC), and the vena contracta (VC) have been reported to be useful for evaluating severity of AR. However, clinical application of these methods has been limited because of the difficulty in clearly imaging the FC and VC. This study aimed to explore new windows for imaging the FC and VC to evaluate AR volumes in patients and to validate this in animals with chronic AR. Forty patients with AR and 17 hemodynamic states in 4 sheep with strictly quantified AR volumes were evaluated. A Toshiba SSH 380A with a 3.75-MHz transducer was used to image the FC and VC. After routine echo Doppler imaging, patients were repositioned in the right lateral decubitus position, and the FC and VC were imaged from high right parasternal windows. In only 15 of the 40 patients was it possible to image clearly and measure accurately the FC and VC from conventional (left decubitus) apical or parasternal views. In contrast, 31 of 40 patients had clearly imaged FC regions and VCs using the new windows. In patients, AR volumes derived from the FC and VC methods combined with continuous velocity agreed well with each other (r = 0.97, mean difference = -7.9 ml +/- 9.9 ml/beat). In chronic animal model studies, AR volumes derived from both the VC and the FC agreed well with the electromagnetically derived AR volumes (r = 0.92, mean difference = -1.3 +/- 4.0 ml/beat). By imaging from high right parasternal windows in the right decubitus position, complementary use of the FC and VC methods can provide clinically valuable information about AR volumes.

Objective and subjective measures of the pharmacodynamic effects of Adderall in the treatment of children with ADHD in a controlled laboratory classroom setting.

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.

Analog classroom assessment of Adderall in children with ADHD.

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.

Evaluation of individual subjects in the analog classroom setting: I. Examples of graphical and statistical procedures for within-subject ranking of responses to different delivery patterns of methylphenidate.

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.

Evaluation of mitral leaflet motion by echocardiography and jet direction by Doppler color flow mapping to determine the mechanisms of mitral regurgitation.

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.

Intraoperative Doppler color flow mapping for decision-making in valve repair for mitral regurgitation. Technique and results in 100 patients.

Mitral valve repair provides substantial advantages over mitral valve replacement in patients with severe mitral regurgitation. However, because of the possibility of persistent regurgitation, an intraoperative technique is needed to provide an immediate and accurate assessment of the adequacy of the repair before closure of the chest. One hundred patients with pure mitral regurgitation were studied with intraoperative epicardial Doppler color flow mapping immediately before and after valve repair. Intraoperative assessment of the severity of mitral regurgitation showed good agreement with preoperative left ventriculography and with standard precordial Doppler echocardiography before and after surgery. Postrepair intraoperative Doppler studies showed satisfactory surgical results in 92 patients. Postrepair intraoperative Doppler studies in the remaining eight patients demonstrated unsatisfactory results: persistent significant regurgitation in four, systolic anterior motion of the mitral valve with dynamic left ventricular outflow tract obstruction in three, and a persistent flail leaflet in one. In six of the eight patients, further surgery was performed during the same thoracotomy. In two patients, the intraoperative postrepair Doppler findings of persistent regurgitation were confirmed on precordial Doppler studies within 5 days, and mitral reoperation was required. Intraoperative epicardial Doppler color flow mapping provided a "safety net" that ensured a successful outcome in all 100 patients by providing the surgeon with a direct means to assess the success of the operation and the need for further surgery.