Mohamed F.A. Aly

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.

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.

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.

The role of ADAMTS13 in acute myocardial infarction : Cause or consequence?

Aims ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a metalloprotease that cleaves von Willebrand factor (VWF). There is considerable evidence that VWF levels increase and ADAMTS13 levels decrease in ST-elevation myocardial infarction (STEMI) patients. It is unclear whether this contributes to no reflow, infarct size, and intramyocardial haemorrhage (IMH). We aimed to determine the role of ADAMTS13 in STEMI patients and to investigate the benefits of recombinant ADAMTS13 (rADAMTS13) in a porcine model of myocardial ischaemia-reperfusion. Methods and results In 49 consecutive percutaneous coronary intervention (PCI)-treated STEMI patients, blood samples were collected directly after through 7 days following PCI. Cardiac magnetic resonance was performed 4–6 days after PCI to determine infarct size and IMH. In 23 Yorkshire swine, the circumflex coronary artery was occluded for 75 min. rADAMTS13 or vehicle was administered intracoronary following reperfusion. Myocardial injury and infarct characteristics were assessed using cardiac enzymes, ECG, and histopathology. In patients with IMH, VWF activity and VWF antigen were significantly elevated directly after PCI and for all subsequent measurements, and ADAMTS13 activity significantly decreased at 4 and 7 days following PCI, in comparison with patients without IMH. VWF activity and ADAMTS13 activity were not related to infarct size. In rADAMTS13-treated animals, no differences in infarct size, IMH, or formation of microthrombi were witnessed compared with controls. Conclusions No correlation was found between VWF/ADAMTS13 and infarct size in patients. However, patients suffering from IMH had significantly higher VWF activity and lower ADAMTS13 activity. Intracoronary administration of rADAMTS13 did not decrease infarct size or IMH in a porcine model of myocardial ischaemia-reperfusion. These data dispute the imbalance in ADAMTS13 and VWF as the cause of no reflow.

Cardiac function and cognition in older community-dwelling cardiac patients

Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown.

Treatment of reperfusion injury with recombinant ADAMTS13 in a porcine model of acute myocardial infarction

Background: No reflow and decreased microvascular perfusion after percutaneous coronary intervention increase morbidity and mortality in ST-elevation myocardial infarction (STEMI) patients. No reflow may be mediated by platelet vessel wall interaction that is governed by von Willebrand factor. ADAMTS13 is a metalloprotease that cleaves von Willebrand factor, thereby reducing its prohemostatic properties. There is considerable evidence that ADAMTS13 levels decrease and von Willebrand factor levels increase in STEMI patients. Recombinant ADAMTS13 has been effective in reducing cerebral infarct size in a murine model of stroke. Aims: In this study recombinant ADAMTS13 was tested as a potential treatment of no reflow in a porcine model of cardiac ischemia and reperfusion. Methods: In 23 female swine (median age 83 days, median weight 30 kg) a balloon was inflated in the circumflex coronary artery for 75 min. Fifteen minutes after reperfusion, an intracoronary bolus of either recombinant ADAMTS13 (400 U/kg, Baxter Innovations Vienna, Austria) or vehicle was given. Results: ADAMTS13 activity significantly increased in treated pigs (from median 18%, IQR 14.5-24.0 to median 324%, IQR 117.0- 384.0, P = 0.003) whereas no change was observed in the control group. Animals were sacrificed 7 days later for histopathology. There was no difference in the size of myocardial necrosis as assessed with plasma Troponin T measurements, continuous 12 leads ECG, macroscopical infarct analysis, and histopathology using phosphotungstic acid-hematoxylin staining. Microvascular obstruction as estimated by staining with anti-CD31/Hematoxylin and counting of vessels and microthrombi was similar for both groups. Conclusions: Intracoronary treatment with recombinant ADAMTS13 did not prevent formation of microthrombi and did not decrease infarct size in this porcine coronary model of ischemia and reperfusion.