Quantification of the area and shunt volume of multiple, circular, and noncircular ventricular septal defects: A 2D/3D echocardiography comparison and real time 3D color Doppler feasibility determination study.

BACKGROUND: Quantification of defect size and shunt flow is an important aspect of ventricular septal defect (VSD) evaluation. This study compared three-dimensional echocardiography (3DE) with the current clinical standard two-dimensional echocardiography (2DE) for quantifying defect area and tested the feasibility of real time 3D color Doppler echocardiography (RT3D-CDE) for quantifying shunt volume of irregular shaped and multiple VSDs. METHODS: Latex balloons were sutured into the ventricles of 32 freshly harvested porcine hearts and were connected with tubing placed in septal perforations. Tubing was varied in area (0.13-5.22 cm²), number (1-3), and shape (circle, oval, crescent, triangle). A pulsatile pump was used to pump "blood" through the VSD (LV to RV) at stroke volumes of 30-70 mL with a stroke rate of 60 bpm. Two-dimensional echocardiography (2DE), 3DE, and RT3D-CDE images were acquired from the right side of the phantom. RESULTS: For circular VSDs, both 2DE and 3DE area measurements were consistent with the actual areas (R² = 0.98 vs 0.99). For noncircular/multiple VSDs, 3DE correlated with the actual area more closely than 2DE (R² = 0.99 vs 0.44). Shunt volumes obtained using RT3D-CDE positively correlated with pumped stroke volumes (R² = 0.96). CONCLUSIONS: Three-dimensional echocardiography (3DE) is a feasible method for determining VSD area and is more accurate than 2DE for evaluating the area of multiple or noncircular VSDs. Real-time 3D color Doppler echocardiography (RT3D-CDE) is a feasible method for quantifying the shunt volume of multiple or noncircular VSDs.

Image-Derived Assessment of Left Ventricular Mass in Fetal Myocardial Hypertrophy by 4-Dimensional Echocardiography: An In Vitro Study.

OBJECTIVES: This study tested the accuracy of new 4-dimensional fetal echocardiography to evaluate left ventricular (LV) mass in an experimental model of fetal myocardial hypertrophy. METHODS: Ten fresh rabbit hearts were studied. Fetal myocardial hypertrophy was simulated by fixing different amounts of myocardial tissue to the LV epicardium. A small latex balloon was mounted on vinyl tubing and fixed within each LV cavity. The proximal end of the tube was attached to a pulsatile pump apparatus. The pump was calibrated to deliver stroke volumes of 2 and 4 mL at stroke rates of 60 and 120 beats per minute (bpm). Four-dimensional data were acquired and analyzed with quantification software. Reference values for LV mass were determined by the displacement method. RESULTS: Echo-derived measurements of LV mass showed good correlations with reference values at all stroke rates and stroke volumes: at 2 mL and 60 bpm, r = 0.95; at 2 mL and 120 bpm, r = 0.95; at 4 mL and 60 bpm, r = 0.93; and at 4 mL and 120 bpm, r = 0.95 (P< .01 for all values). There was also excellent interobserver (r = 0.98; mean difference of -0.32 g; -4.4% of the mean) and intraobserver (r = 0.98; mean difference of -0.28 g; -3.8% of the mean) agreement. CONCLUSIONS: In this controlled in vitro study, high-resolution 4-dimensional echocardiography was shown to accurately assess LV mass and have the potential to evaluate fetal myocardial hypertrophy.

Comprehensive evaluation of cardiac function and detection of myocardial infarction based on a semi-automated analysis using full-volume real time three-dimensional echocardiography.

OBJECTIVE: Quantitative left ventricular mass (LVM) as well as regional strain values may be obtained from full-volume real time 3D echocardiography data via semi-automated feature tracking and represent indices of heart function, both in health and disease. METHODS: Fresh adult porcine and ovine hearts were passively pumped to simulate normal cardiac motion at stroke volumes (SVs) varying from 30 to 70 mL. A 3V-D Matrix probe, interfaced with a GE Vivid E9 ultrasound system, was used to image each heart at baseline conditions and after simulated myocardial infarction (MI). The 4D LV quantification function of EchoPAC PC was used to quantify the LVM and longitudinal and circumferential strain (LS & CS) of LV segments at each SV prior and subsequent to simulated MI. LVM was validated by volumetric displacement, while LS and CS values were compared to sonomicrometry-based strain. RESULTS: Linear regression analyses show excellent correlations in LVM, LS, and CS between the 4D echo and volumetric/sonomicrometric displacement with R(2) values of 0.99, 0.88, and 0.67, respectively. Bland-Altman analyses for all variables validate the compatibility of both methods. It was also determined that EchoPAC PC was able to detect a decrease in LS and CS in the relevant segments between pre- and post-MI at all SVs (P < 0.05). CONCLUSIONS: EchoPAC PC is a robust utility with the ability to accurately obtain quantitative LVM, LS, and CS values from 4D echo volumes and has the potential to improve the yield of clinical studies in cases of suspected MI.

Regional strain determination and myocardial infarction detection by three-dimensional echocardiography with varied temporal resolution.

BACKGROUND: Three-dimensional echocardiography (3DE) is a promising method for strain determination; however, there are temporal resolution concerns. This study aims to evaluate the feasibility and accuracy of 3DE on longitudinal and circumferential strain (LS, CS) determination and infarction detection under variable frame rates (FR) and "heart rates" (stroke rates [SR]) conditions. METHODS: Latex balloons were sewn into the left ventricle (LV) of 20 freshly harvested pig hearts which were then passively driven by a pulsatile pump apparatus at stroke volumes (SV) 30-70 mL. The hearts were pumped at 2 normal limits of human heart rate. Full-volume data were acquired before and after a simulated myocardial infarction (MI) at the 2 most commonly used FRs. LS and CS values were evaluated against sonomicrometry. RESULTS: Longitudinal strain and CS derived from high FR acquisitions showed statistically superior correlations with sonomicrometry data (LS: R(2) = 0.85, CS: R(2) = 0.84) than strain values from low FR (LS: R(2) = 0.78, CS: R(2) = 0.76) (all P < 0.01). After MI induction, LS and CS at different FRs were significantly decreased while maintaining excellent correlations with sonomicrometry data (all P < 0.001). There is no statistical difference of strain values between different SR acquisitions. CONCLUSION: Three-dimensional wall-motion tracking has the ability to accurately determine regional myocardial deformation and detect MI. Different heart rates within a physiologically relevant range have no effect on 3D strain accuracy. Strain values calculated from higher frame rate acquisitions were found to have a slightly better accuracy.

Real Time Three-Dimensional Echocardiographic Evaluations of Fetal Left Ventricular Stroke Volume, Mass, and Myocardial Strain: In Vitro and In Vivo Experimental Study.

BACKGROUND: Left ventricular stroke volume, mass, and myocardial strain are valuable indicators of fetal heart function. This study investigated the feasibility of nongated real time three-dimensional echocardiography (RT3DE) to determine fetal stroke volume (SV), left ventricular mass (LVM), and myocardial strain under different conditions. METHODS: To evaluate fetal hearts, fetal-sized rabbit hearts were used in this study. The in vitro portion of this study was carried out using a balloon inserted into the LV of eight fresh rabbit hearts and driven by a calibrated pulsatile pump. RT3DE volumes were obtained at various pump-set SVs. The in vivo experiments in this study were performed on open-chest rabbits. RT3DE volumes were acquired at the following conditions: baseline, simulated hypervolemia, inferior vena cava (IVC) ligation, and ascending aorta (AAO) ligation. Displacement values and sonomicrometry data were used as references for RT3DE-derived SV, LVM, longitudinal strain (LS), and circumferential strain (CS). RESULTS: Excellent correlations between RT3DE-derived values and reference values were demonstrated and accompanied by high coefficients of determination (R(2) ) for both in vitro and in vivo studies for SV, LVM, LS, and CS (in vitro: SV: R(2)  = 0.98; LVM: R(2)  = 0.97; LS: R(2)  = 0.87, CS: R(2)  = 0.80; in vivo: SV: R(2)  = 0.92; LVM: R(2)  = 0.98; LS: in vivo: R(2)  = 0.84; CS: in vivo: R(2)  = 0.76; all P < 0.05). CONCLUSIONS: RT3DE is capable of quantifying the SV, LVM, and myocardial strain of fetal-sized hearts under different conditions. This nongated RT3DE may aid the evaluation of fetal cardiac function, providing a superior understanding of the progress of fetal heart disorders.

Quantitative assessment of mitral inflow and aortic outflow stroke volumes by 3-dimensional real-time full-volume color flow doppler transthoracic echocardiography: an in vivo study.

OBJECTIVES: Noninvasive quantification of left ventricular (LV) stroke volumes has an important clinical role in assessing circulation and monitoring therapeutic interventions for cardiac disease. This study validated the accuracy of a real-time 3-dimensional (3D) color flow Doppler method performed during transthoracic echocardiography (TTE) for quantifying volume flows through the mitral and aortic valves using a dedicated offline 3D flow computation program compared to LV sonomicrometry in an open-chest animal model. METHODS: Forty-six different hemodynamic states in 5 open-chest pigs were studied. Three-dimensional color flow Doppler TTE and 2-dimensional (2D) TTE were performed by epicardial scanning. The dedicated software was used to compute flow volumes at the mitral annulus and the left ventricular outflow tract (LVOT) with the 3D color flow Doppler method. Stroke volumes by 2D TTE were computed in the conventional manner. Stroke volumes derived from sonomicrometry were used as reference values. RESULTS: Mitral inflow and LVOT outflow derived from the 3D color flow Doppler method correlated well with stroke volumes by sonomicrometry (R = 0.96 and 0.96, respectively), whereas correlation coefficients for mitral inflow and LVOT outflow computed by 2D TTE and stroke volumes by sonomicrometry were R = 0.84 and 0.86. Compared to 2D TTE, the 3D method showed a smaller bias and narrower limits of agreement in both mitral inflow (mean ± SD: 3D, 2.36 ± 2.86 mL; 2D, 10.22 ± 8.46 mL) and LVOT outflow (3D, 1.99 ± 2.95 mL; 2D, 4.12 ± 6.32 mL). CONCLUSIONS: Real-time 3D color flow Doppler quantification is feasible and accurate for measurement of mitral inflow and LVOT outflow stroke volumes over a range of hemodynamic conditions.

Evaluation of stroke volume and ventricular mass in a fetal heart model: a novel four-dimensional echocardiographic analysis.

AIMS: This study aimed to assess the feasibility and accuracy of nongated four-dimensional echocardiography (4DE) for determining left ventricular (LV) stroke volume (SV) and mass in a fetal heart-sized LV model. METHODS: A balloon was inserted into the LV of 20 fresh rabbit hearts and attached to a calibrated pulsatile pump. Ten hearts retaining the right ventricle were imaged in Group A. Ten hearts without the right ventricles (RVs) attached were imaged in Group B. Nongated 4D volumes were obtained using a Philips iU-22 system with an X6-1 matrix probe at SVs ranging from 1 to 5 mL at increments of 1 mL. At each SV, the volume displacement of the heart was measured at end-systole and end-diastole. Mass was determined by displacement at the conclusion of the experiment. RESULTS: The images were analyzed offline by manually tracing endocardial and epicardial boundaries of stacked contours. An excellent correlation in SV and mass between echo-derived values and displacement values was demonstrated and accompanied by high coefficients of determination (R2 ) in both groups (SV: Group A: R2 = 0.9461, Group B: R2 = 0.9811; Mass: Group A: R2 = 0.9223, Group B: R2 = 0.9602; all P < 0.001). Bland-Altman analyses showed a slight overestimation in both groups for both SV and LV mass. CONCLUSIONS: Nongated 4DE was demonstrated to be feasible and that it could accurately define SV and ventricular mass for a fetal heart-sized LV model.

Evaluation of a new 3-dimensional color Doppler flow method to quantify flow across the mitral valve and in the left ventricular outflow tract: an in vitro study.

OBJECTIVES: The aim of this study was to assess the accuracy, feasibility, and reproducibility of determining stroke volume from a novel 3-dimensional (3D) color Doppler flow quantification method for mitral valve (MV) inflow and left ventricular outflow tract (LVOT) outflow at different stroke volumes when compared with the actual flow rate in a pumped porcine cardiac model. METHODS: Thirteen freshly harvested pig hearts were studied in a water tank. We inserted a latex balloon into each left ventricle from the MV annulus to the LVOT, which were passively pumped at different stroke volumes (30-80 mL) using a calibrated piston pump at increments of 10 mL. Four-dimensional flow volumes were obtained without electrocardiographic gating. The digital imaging data were analyzed offline using prototype software. Two hemispheric flow-sampling planes for color Doppler velocity measurements were placed at the MV annulus and LVOT. The software computed the flow volumes at the MV annulus and LVOT within the user-defined volume and cardiac cycle. RESULTS: This novel 3D Doppler flow quantification method detected incremental increases in MV inflow and LVOT outflow in close agreement with pumped stroke volumes (MV inflow, r = 0.96; LVOT outflow, r = 0.96; P < .01). Bland-Altman analysis demonstrated overestimation of both (MV inflow, 5.42 mL; LVOT outflow, 4.46 mL) with 95% of points within 95% limits of agreement. Interobserver variability values showed good agreement for all stroke volumes at both the MV annulus and LVOT. CONCLUSIONS: This study has shown that the 3D color Doppler flow quantification method we used is able to compute stroke volumes accurately at the MV annulus and LVOT in the same cardiac cycle without electrocardiographic gating. This method may be valuable for assessment of cardiac output in clinical studies.

Sympathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias.

Obesity increases the risk of arrhythmias and sudden cardiac death, but the mechanisms are unknown. This study tested the hypothesis that obesity-induced cardiac sympathetic outgrowth and hyperinnervation promotes the development of arrhythmic events. Male Sprague-Dawley rats (250-275 g), fed a high-fat diet (33% kcal/fat), diverged into obesity-resistant (OR) and obesity-prone (OP) groups and were compared with rats fed normal chow (13% kcal/fat; CON). In vitro experiments showed that both OR and OP rats exhibited hyperinnervation of the heart and high sympathetic outgrowth compared with CON rats, even though OR rats are not obese. Despite the hyperinnervation and outgrowth, we showed that, in vivo, OR rats were less susceptible to arrhythmic events after an intravenous epinephrine challenge compared with OP rats. On examining total and stimulus-evoked neurotransmitter levels in an ex vivo system, we demonstrate that atrial acetylcholine content and release were attenuated in OP compared with OR and CON groups. OP rats also expressed elevated atrial norepinephrine content, while norepinephrine release was suppressed. These findings suggest that the consumption of a high-fat diet, even in the absence of overt obesity, stimulates sympathetic outgrowth and hyperinnervation of the heart. However, normalized cardiac parasympathetic nervous system control may protect the heart from arrhythmic events.

Assessment of interventricular dyssynchrony by real time three-dimensional echocardiography: an in vitro study in a porcine model.

BACKGROUND: Loss of synchronous contraction between or within the right and left ventricle (RV, LV) leads to adverse ventricular function. We used real time three-dimensional echocardiography (RT3DE) for evaluation of severity of interventricular dyssynchrony and function in a porcine heart model. METHODS: Six fresh in vitro porcine hearts were used to create a controlled model of LV and RV dyssynchrony using two sets of pulsatile pumps. Synchronized and dyssynchronized pump settings were used with two different dyssynchronized settings: LV filled first and RV filled first. RESULTS: There was good correlation between actual measurement and RT3DE for interventricular time difference (r = 0.95, P < 0.0001) and stroke volume (SV) for LV and RV (0.89, 0.85; P < 0.0001, respectively). RT3DE data showed a small but significant underestimation for actual volume (P < 0.05). The intra- and interobserver variabilities are 2.9 +/- 1.5% and 3.1 +/- 5.4% for LV and RV SVs, and 1.7 +/- 2.4% and 2.2 +/- 3.2% for time differences by RT3DE. There was significant difference in RV SV between synchrony and dyssynchrony when the RV filled first (P < 0.05), but not in other groups. The same pattern was found in RT3DE derived SVs (synchrony versus dyssynchrony with RV filled first, P < 0.05). CONCLUSIONS: There is no compromise in LV SV during interventricular dyssynchrony; but RV SV was significantly diminished when the RV filled first. RT3DE is a feasible, robust and reproducible method to identify interventricular dyssynchrony and to evaluate ventricular SVs.

Mitigation of Variability among 3D Echocardiography-Derived Regional Strain Values Acquired by Multiple Ultrasound Systems by Vendor Independent Analysis.

INTRODUCTION: This study compared the variability of 3D echo derived circumferential and longitudinal strain values computed from vendor-specific and vendor-independent analyses of images acquired using ultrasound systems from different vendors. METHODS: Ten freshly harvested porcine hearts were studied. Each heart was mounted on a custom designed phantom and driven to simulate normal cardiac motion. Cardiac rotation was digitally controlled and held constant at 5°, while pumped stroke volume (SV) ranged from 30-70ml. Full-volume image data was acquired using three different ultrasound systems from different vendors. The image data was analyzed for longitudinal and circumferential strains (LS, CS) using both vendor-specific and vendor-independent analysis packages. RESULTS: Good linear relationships were observed for each vendor-specific analysis package for both CS and LS at the mid-anterior segment, with correlation coefficients ranging from 0.82-0.91 (CS) and 0.86-0.89 (LS). Comparable linear regressions were observed for results determined by a vendor independent program (CS: R = 0.82-0.89; LS: R = 0.86-0.89). Variability between analysis packages was examined via a series of ANOVA tests. A statistical difference was found between vendor-specific analysis packages (p<0.001), while no such difference was observed between ultrasound systems when using the vendor-independent program (p>0.05). CONCLUSIONS: Circumferential and longitudinal regional strain values differ when quantified by vendor-specific analysis packages; however, this variability is mitigated by use of a vendor-independent quantification method. These results suggest that echocardiograms acquired using different ultrasound systems could be meaningfully compared using vendor-independent software.

Quantification of Shunt Volume Through Ventricular Septal Defect by Real-Time 3-D Color Doppler Echocardiography: An in Vitro Study.

Quantification of shunt volume is important for ventricular septal defects (VSDs). The aim of the in vitro study described here was to test the feasibility of using real-time 3-D color Doppler echocardiography (RT3-D-CDE) to quantify shunt volume through a modeled VSD. Eight porcine heart phantoms with VSDs ranging in diameter from 3 to 25 mm were studied. Each phantom was passively driven at five different stroke volumes from 30 to 70 mL and two stroke rates, 60 and 120 strokes/min. RT3-D-CDE full volumes were obtained at color Doppler volume rates of 15, 20 and 27 volumes/s. Shunt flow derived from RT3-D-CDE was linearly correlated with pump-driven stroke volume (R = 0.982). RT3-D-CDE-derived shunt volumes from three color Doppler flow rate settings and two stroke rate acquisitions did not differ (p > 0.05). The use of RT3-D-CDE to determine shunt volume though VSDs is feasible. Different color volume rates/heart rates under clinically/physiologically relevant range have no effect on VSD 3-D shunt volume determination.