Sebastiaan A. Kleijn

Reliability of left ventricular volumes and function measurements using three-dimensional speckle tracking echocardiography

AIMS Although the accuracy of three-dimensional speckle tracking echocardiography (STE) to quantify left ventricular (LV) volumes and function has been demonstrated, its reliability has not been studied in great detail. The aim of the study was to determine inter-observer, intra-observer, and test-retest reliability of echocardiographic measurements of LV volumes and function using three-dimensional STE. METHODS AND RESULTS A total of 140 consecutive patients presenting for routine echocardiographic examination underwent three-dimensional STE. Twenty-three of the 140 patients (16%) were excluded from the analysis due to atrial fibrillation or insufficient image quality. In the remaining 117 patients [69 males, age 59 ± 16 years, ejection fraction (EF) 51 ± 13%], intra-observer and inter-observer reliability of LV volumes, EF, and global and segmental strain measurements was determined, whereas test-retest reliability was assessed in a subgroup of 50 patients. LV volumes and EF measurements demonstrated good reliability [intraclass correlation coefficient (ICC): 0.85-0.99; standard error of measurement (SEM): 3.1-9.2 mL and 1.7-4.0%, respectively]. Reliability of global circumferential strain measurements (ICC: 0.85-0.97; SEM: 1.4-2.6%) was superior to longitudinal (ICC: 0.66-0.92; SEM: 1.0-2.1%) and radial strain measurements (ICC: 0.52-0.88; SEM: 4.4-8.1%), with similar results found for segmental strain measurements (P < 0.001 for all). Reliability was not significantly affected by the image quality or temporal resolution of 3D data sets for any parameter. CONCLUSION Good intra-observer, inter-observer, and test-retest reliability support the use of three-dimensional STE for routine evaluation of LV volumes and EF. Global and segmental circumferential strain measurements also demonstrate high reliability, whereas analysis by a single observer is currently recommended for longitudinal and radial strain due to limited inter-observer and test-retest reliability.

Comparison between three-dimensional speckle-tracking echocardiography and cardiac magnetic resonance imaging for quantification of left ventricular volumes and function

AIMS We evaluated the accuracy of three-dimensional speckle-tracking echocardiography (3DSTE) to evaluate left ventricular (LV) volumes, ejection fraction (EF), and global circumferential strain (CS) in comparison with cardiac magnetic resonance imaging (MRI) in a healthy population. METHODS AND RESULTS A total of 45 out of 50 consecutive healthy subjects (38 males, age 45 ± 15 years) successfully underwent both 3DSTE and MRI on the same day. Three-dimensional echocardiography data sets were analysed using speckle tracking to measure LV end-diastolic and end-systolic volumes, EF, and global CS. With MRI, the method of discs approximation was used to obtain volumes and the EF, whereas CS was acquired using myocardial tissue tagging. Inter-technique comparisons included regression and the Bland-Altman analysis. For quantification of LV volumes, 3DSTE correlated well with MRI (r: 0.75-0.81), but volumes were significantly underestimated with relatively large biases (13-34 mL) and wide limits of agreement (SD: 11-25 mL). However, excellent accuracy was revealed for measurement of EF by 3DSTE with a good correlation (r: 0.91), minimal bias, and narrow limits of agreement (0.6 ± 1.7%) compared with MRI. For measurement of CS, a large mean bias was found between techniques (10.0%), despite narrow limits of agreement (SD: 1.7%) and a good correlation between techniques (r: 0.80). CONCLUSION Although 3DSTE-derived LV volumes are underestimated in most patients compared with MRI, measurement of the LVEF revealed excellent accuracy. Measurements of CS were systematically greater (i.e. more negative) with 3DSTE than MRI, which likely reflects various inter-technique differences that preclude direct comparability of their measurements.

Assessment of Intraventricular Mechanical Dyssynchrony and Prediction of Response to Cardiac Resynchronization Therapy: Comparison between Tissue Doppler Imaging and Real-Time Three-Dimensional Echocardiography

OBJECTIVE We studied the comparability of left ventricular (LV) mechanical dyssynchrony assessment by tissue Doppler imaging (TDI) and real-time three-dimensional echocardiography (RT3DE) in patients with a wide range of LV ejection fractions and different causes of cardiomyopathy. In addition, we evaluated the ability of both techniques to predict response to cardiac resynchronization therapy (CRT). METHODS A total of 90 patients and 30 healthy volunteers underwent both TDI and RT3DE. A subgroup of 27 patients underwent CRT and were evaluated before and 6 months after implantation. Mechanical dyssynchrony was measured with TDI using the standard deviation of time to peak systolic tissue velocity of 12 LV myocardial segments. With RT3DE, the standard deviation of time from QRS onset to minimal volume of 16 LV subvolumes was assessed. Indicators of response to CRT were a clinical improvement of >or= 1 New York Heart Association functional class, and reverse remodeling defined as a reduction of >or= 15% in LV end-systolic volume at 6 months. RESULTS A moderate correlation (r = 0.581, P < .001) was observed between TDI and RT3DE. No significant difference in the presence of mechanical dyssynchrony by TDI and RT3DE was observed (53% vs 48%, respectively). Agreement between techniques was comparable between patients with ischemic and nonischemic cardiomyopathy. However, up to 30% nonagreement between the 2 techniques was found, depending on the severity of LV dysfunction. Of the 27 patients undergoing CRT, clinical response was observed in 70% of patients, whereas reverse remodeling occurred in 63% of patients. All baseline characteristics were similar between responders and nonresponders, except for mechanical dyssynchrony assessed by RT3DE, which was significantly higher in responders compared with nonresponders (10.1% +/- 2.6% vs 5.1% +/- 1.2% for clinical response, P < .001; 10.0% +/- 2.8% vs 6.3% +/- 2.3% for reverse remodeling, P = .001). By applying previously defined cutoff values, receiver operating characteristic curve analysis demonstrated a sensitivity of 58% with a specificity of 50% for TDI and a sensitivity of 95% with a specificity of 87% for RT3DE to predict clinical response to CRT. For prediction of reverse remodeling after CRT, sensitivity and specificity were 59% and 50% for TDI, and 88% and 60% for RT3DE, respectively. The optimal cutoff value for systolic dyssynchrony index by RT3DE of 6.7% yielded a sensitivity of 90% with a specificity of 87% to predict clinical response, and a sensitivity of 88% with a specificity of 70% to predict reverse remodeling. CONCLUSION Marked differences between techniques are found for the presence of mechanical dyssynchrony when current cutoff values are applied, making interchangeability of these techniques uncertain. Assessment of mechanical dyssynchrony by RT3DE might be an appropriate alternative to TDI for accurate prediction of response to CRT.

Comparison Between Direct Volumetric and Speckle Tracking Methodologies for Left Ventricular and Left Atrial Chamber Quantification by Three-Dimensional Echocardiography

In an era of rapidly expanding and evolving 3-dimensional echocardiographic (3DE) technology, 1 of the issues facing the 3DE quantification of chamber volumes and function is that different software vendors use different methodologies and algorithms. The aim of this study was to evaluate the comparability and reproducibility of 3DE direct volumetric and speckle-tracking methods for left ventricular (LV) and left atrial (LA) chamber quantification. A total of 120 subjects (mean age 53 ± 17 years, 65% men), including 88 unselected patients and 32 healthy volunteers, underwent 3DE acquisitions and analysis using direct volumetric and speckle-tracking methods successively. Measurements of LV and LA volumes and LV function were compared between the 2 3DE methods. Additionally, intraobserver and interobserver reproducibility was assessed in 40 randomly selected patients. Measurements of LV end-diastolic volume, end-systolic volume, and ejection fraction by 3DE direct volumetric and 3DE speckle-tracking methods were comparable, with good correlations (r = 0.98, r = 0.98, and r = 0.87, respectively), small biases, and narrow limits of agreement (-1 ± 8 ml, -1 ± 8 ml, and 0 ± 6%, respectively). For measurements of LA end-systolic volume and end-diastolic volume, similar correlations (r = 0.96 for both), small biases, and narrow limits of agreement (-2 ± 6 and -1 ± 5 ml, respectively) were found between the 2 methods. Intraobserver and interobserver reproducibility for LV and LA quantification were comparable for the 2 methods. In conclusion, 3DE direct volumetric and speckle-tracking methods give comparable and reproducible quantification of LV and LA volumes and function, making interchangeable application a viable option in daily clinical practice.

A meta-analysis of left ventricular dyssynchrony assessment and prediction of response to cardiac resynchronization therapy by three-dimensional echocardiography

AIMS In a time of controversy regarding the use of echocardiography for assessment of left ventricular (LV) dyssynchrony and prediction of response to cardiac resynchronization therapy (CRT), this meta-analysis aimed to evaluate the feasibility and reliability of LV dyssynchrony assessment by three-dimensional echocardiography (3DE), determine clinically useful reference values in healthy subjects and heart failure patients, and examine the accuracy of 3DE to predict response to CRT. METHODS AND RESULTS A total of 73 studies that evaluated the assessment of LV dyssynchrony by 3DE were eligible. The systolic dyssynchrony index (SDI) for 16 segments, being the predominant 3DE dyssynchrony parameter, was used for data pooling. Results demonstrated that LV dyssynchrony assessment by 3DE is feasible in 94% of studied subjects [95% confidence interval (CI): 92-95%)]. Pooled estimates of intraclass correlation coefficients (ICC) and limits of agreement (LoA) demonstrated that SDI has good interobserver (ICC: 0.92, LoA: 4.07%) and intraobserver reliability (ICC: 0.95, LoA: 2.10%). Reference values of SDI in healthy subjects, heart failure patients in general, and patients eligible for CRT were 2.7 ± 0.9%, 9.8 ± 3.9%, and 10.7 ± 3.6%, respectively. Meta-regression analysis demonstrated that reference values of SDI in healthy subjects significantly differed between different software [1.80% (95% CI: 0.55-3.05%), P< 0.001]. In patients eligible for CRT, SDI had good accuracy to predict treatment response with a weighted mean cut-off value of 9.8% and pooled estimates for sensitivity and specificity of 93% (95% CI: 89-97%) and 75% (95% CI: 58-93%), respectively. CONCLUSION 3DE is a feasible and reliable tool for assessment of LV dyssynchrony and may have additional value to current selection criteria for accurate prediction of response to CRT.

Normal reference values of left ventricular strain using three-dimensional speckle tracking echocardiography: results from a multicentre study

AIMS Three-dimensional (3D) speckle tracking echocardiography (3DSTE) has been shown to be an accurate and reliable clinical tool for the evaluation of global and regional left ventricular (LV) function through strain analysis, but the absence of normal values has precluded its widespread use in clinical practice. The aim of this prospective multicentre study was to establish normal reference values of LV strain parameters using 3DSTE in a large healthy population. METHODS AND RESULTS A total of 303 healthy subjects (156 males [51%], between 18 and 82 years of age, ejection fraction [EF] 61 ± 3%), stratified to provide approximately equal proportions of healthy subjects of 18-30, 31-40, 41-50, 51-60, and >60 years of age, underwent 3DSTE. Data were analysed for LV volumes, EF, mass, and global and regional circumferential, longitudinal, radial, and area strain. Significant but small differences between men and women were found for longitudinal and area strains, as well as between different age groups for all LV strain parameters. However, large differences in normal values were observed between different segments, walls, and levels of the LV for radial and longitudinal strains, whereas circumferential and area strains demonstrated generally consistent normal ranges across the LV. CONCLUSIONS Normal ranges of global and regional LV strain using 3DSTE have been established for clinical use. Differences in the magnitude of LV strain are present between men and women as well as different age groups. Moreover, there are differences between different segments, walls, and levels as part of the functional non-uniformity of the normal LV that necessitates the use of segment-specific normal ranges for radial and longitudinal strains. Circumferential and area strains demonstrate the most consistent normal ranges overall.

Prediction of long-term outcome of cardiac resynchronization therapy by acute pressure-volume loop measurements.

Invasive assessment of acute haemodynamic response to biventricular pacing has been proposed as a tool to determine individual response and to optimize the effects of CRT. However, the long‐term results of this approach have been poorly studied. The present study relates acute haemodynamic effects of CRT to long‐term outcome.

ULTRASOUND ENHANCED PREHOSPITAL THROMBOLYSIS USING MICROBUBBLES INFUSION IN PATIENTS WITH ACUTE ST ELEVATION MYOCARDIAL INFARCTION: PILOT OF THE SONOLYSIS STUDY

In animal studies, transthoracic ultrasound and microbubbles have shown to dissolve thrombi in ST elevation myocardial infarction (STEMI). To examine this effect in patients, we have initiated the Sonolysis trial. In this pilot study of 10 patients with a first acute STEMI, we investigated the safety and feasibility of this trial. After pretreatment in the ambulance, five patients were randomized to receive microbubbles with three-dimensional (3-D) guided high mechanical index impulses (1.18) for 15 min, whereas the control group received placebo without ultrasound. Subsequently, primary percutaneous coronary intervention (PPCI) was performed, if indicated. All patients successfully underwent study treatment and PPCI. No significant difference between treatment and control group in safety (minor adverse events 2/5 vs. 2/5, p = NS) and outcome (TIMI III flow 3/5 vs. 1/5 respectively, p = 0.23) was recorded. These results demonstrate that the study protocol is feasible in the acute cardiac care setting and safe during treatment and follow-up.

Comparison of three-dimensional echocardiographic software packages for assessment of left ventricular mechanical dyssynchrony and prediction of response to cardiac resynchronization therapy

AIMS We directly compared TomTec and QLAB software packages for the three-dimensional echocardiographic (3DE) assessment of left ventricular (LV) dyssynchrony including their ability to predict response to cardiac resynchronization therapy (CRT) in patients with ischaemic and non-ischaemic cardiomyopathy. METHODS AND RESULTS A total of 140 heart failure patients with the LVEF ≤35% and 60 healthy volunteers underwent 3DE. A subgroup of 60 patients underwent CRT and were evaluated before and 6-12 months after implantation. The systolic dyssynchrony index (SDI) was derived from the dispersion of time to minimum regional volume for all 16 LV segments and measured with both software packages and compared using Pearsons correlation and Bland-Altman analysis. Measurements of SDI were significantly higher using TomTec compared with QLAB in both patients (10.9 ± 3.8 vs. 9.7 ± 3.9, P < 0.001) and healthy volunteers (4.1 ± 0.8 vs. 2.4 ± 1, P < 0.001), with large biases and wide limits of agreement. A moderate correlation (r = 0.65, P < 0.001) was observed between both software packages in patients while their inter-observer and intra-observer reliability were good. Of the 60 patients undergoing CRT, reverse remodelling as a measure of response was observed in 41 patients (68%). The optimal SDI cut-off value to predict response to CRT was higher for TomTec than for QLAB (8.8 vs.7.3%, P < 0.001) and demonstrated better sensitivity and specificity (93 and 61%, respectively) compared with QLAB (88 and 33%, respectively). Response prediction in patients with non-ischaemic cardiomyopathy was excellent with a sensitivity and specificity of 95 and 100% for TomTec and 70 and 83% for QLAB using similar cut-off values of 9.1 and 9.2%, respectively. CONCLUSION Different 3DE software packages for the assessment of mechanical dyssynchrony should not be used interchangeably until better software standardization is achieved. Dyssynchrony assessment with 3DE for the prediction of response to CRT seems particularly useful in patients with non-ischaemic cardiomyopathy.

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