Evaluation of Intracardiac Pressures Using Subharmonic-aided Pressure Estimation with Sonazoid Microbubbles.

Purpose To investigate if the right ventricular (RV) systolic and left ventricular (LV) diastolic pressures can be obtained noninvasively using the subharmonic-aided pressure estimation (SHAPE) technique with Sonazoid microbubbles. Materials and Methods Individuals scheduled for a left and/or right heart catheterization were prospectively enrolled in this institutional review board-approved clinical trial from 2017 to 2020. A standard-of-care catheterization procedure was performed by advancing fluid-filled pressure catheters into the LV and aorta (n = 25) or RV (n = 22), and solid-state high-fidelity pressure catheters into the LV and aorta in a subset of participants (n = 18). Study participants received an infusion of Sonazoid microbubbles (GE HealthCare), and SHAPE data were acquired using a validated interface developed on a SonixTablet (BK Medical) US scanner, synchronously with the pressure catheter data. A conversion factor, derived using cuff-based pressure measurements with a SphygmoCor XCEL PWA (ATCOR) and subharmonic signal from the aorta, was used to convert the subharmonic signal into pressure values. Errors between the pressure measurements obtained using the SHAPE technique and pressure catheter were compared. Results The mean errors in pressure measurements obtained with the SHAPE technique relative to those of the fluid-filled pressure catheter were 1.6 mm Hg ± 1.5 [SD] (P = .85), 8.4 mm Hg ± 6.2 (P = .04), and 7.4 mm Hg ± 5.7 (P = .09) for RV systolic, LV minimum diastolic, and LV end-diastolic pressures, respectively. Relative to the measurements with the solid-state high-fidelity pressure catheter, the mean errors in LV minimum diastolic and LV end-diastolic pressures were 7.2 mm Hg ± 4.5 and 6.8 mm Hg ± 3.3 (P ≥ .44), respectively. Conclusion These results indicate that SHAPE with Sonazoid may have the potential to provide clinically relevant RV systolic and LV diastolic pressures. Keywords: Ultrasound-Contrast, Cardiac, Aorta, Left Ventricle, Right Ventricle ClinicalTrials.gov registration no.: NCT03245255 © RSNA, 2024.

Noninvasive Evaluation of Cardiac Chamber Pressures Using Subharmonic-Aided Pressure Estimation With Definity Microbubbles.

BACKGROUND: Noninvasive and accurate assessment of intracardiac pressures has remained an elusive goal of noninvasive cardiac imaging. OBJECTIVES: The purpose of this study was to investigate if errors in intracardiac pressures obtained noninvasively using contrast microbubbles and the subharmonic-aided pressure estimation (SHAPE) technique are <5 mm Hg. METHODS: In a nonrandomized institutional review board-approved clinical trial (NCT03243942), patients scheduled for a left-sided and/or right-sided heart catheterization procedure and providing written informed consent were included. A standard-of-care catheterization procedure was performed advancing clinically used pressure catheters into the left and/or right ventricles and/or the aorta. After pressure catheter placement, patients received an infusion of Definity microbubbles (n = 56; 2 vials diluted in 50 mL of saline; infusion rate: 4-10 mL/min) (Lantheus Medical Imaging). Then SHAPE data was acquired using a validated interface developed on a SonixTablet scanner (BK Medical Systems) synchronously with the pressure catheter data. A conversion factor (mm Hg/dB) was derived from SHAPE data and measurements with a SphygmoCor XCEL PWA device (ATCOR Medical) and was combined with SHAPE data from the left and/or the right ventricles to obtain clinically relevant systolic and diastolic ventricular pressures. RESULTS: The mean value of absolute errors for left ventricular minimum and end diastolic pressures were 2.9 ± 2.0 and 1.7 ± 1.2 mm Hg (n = 26), respectively, and for right ventricular systolic pressures was 2.2 ± 1.5 mm Hg (n = 11). Two adverse events occurred during Definity infusion; both were resolved. CONCLUSIONS: These results indicate that the SHAPE technique with Definity microbubbles is encouragingly efficacious for obtaining intracardiac pressures noninvasively and accurately. (Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement; NCT03243942).

Comparing Central Aortic Pressures Obtained Using a SphygmoCor Device to Pressures Obtained Using a Pressure Catheter.

BACKGROUND: This study compared aortic pressures estimated using a SphygmoCor XCEL PWA device (ATCOR, Naperville, IL) noninvasively with aortic pressures obtained using pressure catheters during catheterization procedures and analyzed the impact of a linear-fit function on the estimated pressure values. METHODS: One hundred and thirty-six patients scheduled for cardiac catheterization procedure were enrolled in IRB approved studies. Catheterization procedures were performed according to standard-of-care to acquire aortic pressure measurements. Immediately after the catheterization procedure with the pressure catheters removed, while the patients were still in the catheterization laboratory, central aortic pressures were estimated with the SphygmoCor device (using its inbuilt transfer function). The error between measured and estimated aortic pressures was evaluated using Bland-Altman analysis (n = 93). A linear-fit was performed between the measured and estimated pressures, and using the linear equation the error measurements were repeated. A bootstrap analysis was performed to test the generalizability of the linear-fit function. In a subset of cases (n = 13), central aortic pressure values were also obtained using solid-state high-fidelity catheters (Millar, Houston, TX), and the error measurements were repeated. RESULTS: The magnitude of errors between the measured and estimated aortic pressures (mean errors >6.4 mm Hg; mean errors >8.0 mm Hg in the subset) were reduced to less than 1 mm Hg after using the linear-fit function derived in this study. CONCLUSIONS: For the population examined in this study, the SphygmoCor data must be used with the linear-fit function to obtain aortic pressures that are comparable to the measurements obtained using pressure catheters. CLINICAL TRIALS REGISTRATION: Trial Numbers NCT03243942 and NCT03245255.

Non-Invasive Intra-cardiac Pressure Measurements Using Subharmonic-Aided Pressure Estimation: Proof of Concept in Humans.

This study evaluated the feasibility of employing non-invasive intra-cardiac pressure estimation using subharmonic signals from ultrasound contrast agents in humans. This institutional review board-approved proof-of-concept study included 15 consenting patients scheduled for left and right heart catheterization. During the catheterization procedure, Definity was infused intra-venously at 4-10 mL/min. Ultrasound scanning was performed with a Sonix RP using pulse inversion, three incident acoustic output levels and 2.5-MHz transmit frequency. Radiofrequency data were processed and subharmonic amplitudes were compared with the pressure catheter data. The correlation coefficient between subharmonic signals and pressure catheter data ranged from -0.3 to -0.9. For acquisitions with optimum acoustic output, pressure errors between the subharmonic technique and catheter were as low as 2.6 mmHg. However, automatically determining optimum acoustic output during scanning for each patient remains to be addressed before clinical applicability can be decided.

Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures.

Right heart catheterization is often required to monitor intra-cardiac pressures in a number of disease states. Ultrasound contrast agents can produce pressure modulated subharmonic emissions that may be used to estimate right ventricular (RV) pressures. A technique based on subharmonic acoustic emissions from ultrasound contrast agents to track RV pressures noninvasively has been developed and its clinical potential evaluated. The subharmonic signals were obtained from the aorta, RV, and right atrium (RA) of five anesthetized closed-chest mongrel dogs using a SonixRP ultrasound scanner and PA4-2 phased array. Simultaneous pressure measurements were obtained using a 5-French solid state micromanometer tipped catheter. Initially, aortic subharmonic signals and systemic blood pressures were used to obtain a calibration factor in units of millimeters of mercury per decibel. This factor was combined with RA pressures (that can be obtained noninvasively) and the acoustic data from the RV to obtain RV pressure values. The individual calibration factors ranged from -2.0 to -4.0 mmHg/dB. The subharmonic signals tracked transient changes in the RV pressures within an error of 0.6 mmHg. Relative to the catheter pressures, the mean errors in estimating RV peak systolic and minimum diastolic pressures, and RV relaxation [isovolumic negative derivative of change in pressure over time (-dP/dt)] by use of the subharmonic signals, were -2.3 mmHg, -0.8 mmHg, and 2.9 mmHg/s, respectively. Overall, acoustic estimates of RV peak systolic and minimum diastolic pressures and RV relaxation were within 3.4 mmHg, 1.8 mmHg, and 5.9 mmHg/s, respectively, of the measured pressures. This pilot study demonstrates that subharmonic emissions from ultrasound contrast agents have the potential to noninvasively track in vivo RV pressures with errors below 3.5 mmHg.

Noninvasive LV pressure estimation using subharmonic emissions from microbubbles.

To develop a new noninvasive approach to quantify left ventricular (LV) pressures using subharmonic emissions from microbubbles, an ultrasound scanner was used in pulse inversion grayscale mode; unprocessed radiofrequency data were obtained with pulsed wave Doppler from the aorta and/or LV during Sonazoid infusion. Subharmonic data (in dB) were extracted and processed. Calibration factor (mm Hg/dB) from the aortic pressure was used to estimate LV pressures. Errors ranged from 0.19 to 2.50 mm Hg when estimating pressures using the aortic calibration factor, and were higher (0.64 to 8.98 mm Hg) using a mean aortic calibration factor. Subharmonic emissions from ultrasound contrast agents have the potential to noninvasively monitor LV pressures.

Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles.

The purpose of this study was to develop and validate a noninvasive pressure estimation technique based on subharmonic emissions from a commercially available ultrasound contrast agent and scanner, unlike other studies that have either adopted a single-element transducer approach and/ or use of in-house contrast agents. Ambient pressures were varied in a closed-loop flow system between 0 and 120 mmHg and were recorded by a solid-state pressure catheter as the reference standard. Simultaneously, the ultrasound scanner was operated in pulse inversion mode transmitting at 2.5 MHz, and the unprocessed RF data were captured at different incident acoustic pressures (from 76 to 897 kPa). The subharmonic data for each pulse were extracted using band-pass filtering with averaging, and subsequently processed to eliminate noise. The incident acoustic pressure most sensitive to ambient pressure fluctuations was determined, and then the ambient pressure was tracked over 20 s. In vivo validation of this technique was performed in the left ventricle (LV) of 2 canines. In vitro, the subharmonic signal could track ambient pressure values with r(2) = 0.922 (p < 0.001), whereas in vivo, the subharmonic signal tracked the LV pressures with r(2) > 0.790 (p < 0.001) showing a maximum error of 2.84 mmHg compared with the reference standard. In conclusion, a subharmonic ultrasound-based pressure estimation technique, which can accurately track left ventricular pressures, has been established.