Echocardiographic techniques for the assessment of cardiac function have been limited by an inability to consistently measure intracardiac pressures noninvasively. If we can establish that insonation of contrast microbubbles and analysis of their subharmonic oscillations can accurately and continuously measure intracardiac pressures, many of the physical limitations of echocardiography would be overcome. Our group has demonstrated that the nonlinearly generated, subharmonic signal components from microbubble- based ultrasound contrast agents can provide an excellent indication of the hydrostatic pressure variation (from 0 to 200 mmHg). Based on these results, a quantitative technique called SubHarmonic-Aided Pressure Estimation (SHAPE) was proposed and investigated. SHAPE estimates internal pressure variations by transmitting at one frequency, but measuring signal response only at the subharmonic frequency. This technique has the potential to noninvasively measure changes in pressure and has been validated in animals. Our ongoing feasibility study provides proof-of-concept for SHAPE in humans. The fundamental hypothesis of this project is that intracardiac pressure changes in patients scheduled for a left and/or right heart catheterization can be measured using SHAPE in real-time and that results will compare favorably with catheter based pressure measurements. Thus, essential information regarding the functional integrity of the cardiovascular system can be provided noninvasively in real-time, which will fundamentally alter the clinical management of such patients. Initially, the SHAPE algorithm incorporating optimum incident acoustic pressure selection and processing of the subharmonic signals will be implemented on a state-of-the-art ultrasound scanner (SonixTablet, Analogic Corporation, Peabody, MA) for real-time SHAPE pressure measurements, which will be verified in vitro (Specific Aim 1). Next, we will study cardiac pressure changes in patients scheduled for a left and/or right heart catheterization using SHAPE and correlate results to catheter based pressure measurements and establish if the errors in pressure measurements using SHAPE are within 5 mmHg of the catheter-based pressure data (Specific Aim 2). Finally for a set of patients referred for clinically indicated left heart catheterization, we will compare the ventricular relaxation rate (peak isovolumic -dP/dt) and relaxation time constant (tau or ?) in addition to the clinically important ventricular systolic ad diastolic pressures obtained using SHAPE and high fidelity micromanometer-tipped catheters (Mikro-Cath, Millar, Inc. Houston, TX) (Specific Aim 3). In conclusion, this study aims to provide an improved and clinically useful, real-time implementation of the innovative SHAPE algorithm on a state-of- the-art, commercial ultrasound scanner and to challenge the clinical paradigm of invasively-determined, pressure measurements in patients scheduled for cardiac catheterization by noninvasively evaluating intracardiac pressures in humans.

Public Health Relevance

There are about 83.6 million Americans suffering from more than one type of cardiovascular disease with heart failure currently affecting more than 5 million Americans. Pressure measurement within the chambers of the heart provides essential information for the assessment and management of heart failure patients and those in cardiogenic shock or other circulatory compromise. However, the current standard of care is invasive Swan-Ganz pressure catheter measurements and this study aims to challenge the clinical paradigm on using such measurements in cardiac patients by developing a clinically useful, real-time implementation of an ultrasound contrast agent based algorithm for pressure estimation and compare it to Swan-Ganz results in a human pilot study.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Exploratory/Developmental Grants (R21)
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Medical Imaging Study Section (MEDI)
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Lee, Albert
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Thomas Jefferson University
Schools of Medicine
United States
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Dave, Jaydev K; Kulkarni, Sushmita V; Pangaonkar, Purva P et al. (2017) Non-Invasive Intra-cardiac Pressure Measurements Using Subharmonic-Aided Pressure Estimation: Proof of Concept in Humans. Ultrasound Med Biol 43:2718-2724