Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement

NCT03243942 | Completed Phase 2 FDA Drug

• 1 other identifier: 15SDG25740015
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The fundamental hypothesis of this project is that real-time intracardiac pressures can be monitored and quantified noninvasively in humans using a novel contrast-enhanced ultrasound technique called subharmonic-aided pressure estimation (SHAPE).This study will use contrast echocardiography to assess the accuracy of SHAPE compared to simultaneously acquired intracardiac pressures measured invasively during cardiac catheterization. This study is designed to verify that contrast echocardiography using the SHAPE method, already proven in a canine model and tested in a human pilot study can be used as a surrogate for cardiac catheterization with sufficient accuracy to allow clinical applicability in humans.

Conditions

Cardiac Catheterization; Blood Pressure; Heart Ventricles; Echocardiography; Heart Failure

Keywords

pressure measurements; blood pressure; contrast echocardiography; ventricular pressures; catheterization

Outcome Measures

Primary Outcomes (2)

• Agreement between SHAPE and pressure catheter measurements

  Correlation

  up to 1 day

• Error between SHAPE and pressure catheter measurements

  ANOVA/Post-hoc comparisons

  up to 1 day

Study Arms (1)

Definity for pressure measurements

EXPERIMENTAL

2 vials of activated Definity mixed with 50 ml saline. As per manufacturer's recommendation the infusion rate may vary between 4-10 ml/min (to provide diagnostic intracardiac contrast visibility).

Drug: Definity

Interventions

Definity DRUG

Whenever a patient undergoes cardiac catheterization, which routinely includes intracardiac pressure monitoring using a pressure catheter, as part of their standard clinical care and agrees to participate in the study, we will acquire research data. With Definity infusion, SHAPE algorithm will be initiated to determine optimum acoustic pressure. Then, at the optimum acoustic pressure SHAPE specific data will be acquired from the cardiac chambers and aorta synchronously with the pressures recorded by the catheter (as a part of the patient's standard of care). After acquiring the ultrasound imaging data, the remainder of the heart catheterization will be completed by the attending cardiologist according to the patients' standard of care.

Definity for pressure measurements

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be scheduled for a cardiac catheterization procedure
• Adult patients over the age of 21
• Acceptable baseline echocardiographic images in the supine position
• If a female of child-bearing potential, must have a negative pregnancy test
• Provide written informed consent

You may not qualify if:

• Clinically unstable patients, e.g., those who are clinically in decompensated heart failure or having active chest pain or presenting for admission with an unstable anginal syndrome
• Patients in whom introduction of a catheter into the left ventricle is contraindicated or would potentially be dangerous, e.g., patients with active ventricular arrhythmias or with significant aortic valve stenosis where crossing the aortic valve may be difficult and not clinically necessary
• Patients with anatomic right-to-left, bi-directional, or transient right-to-left cardiac shunts where Definity could traverse as a bolus
• Patients with known hypersensitivity to Definity
• Females who are pregnant or nursing

Sponsors & Collaborators

• Thomas Jefferson University: lead
• American Heart Association: collaborator
• Lantheus Medical Imaging: collaborator

Study Sites (1)

Thomas Jefferson University and Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (12)

• Dave JK, Halldorsdottir VG, Eisenbrey JR, Liu JB, McDonald ME, Dickie K, Leung C, Forsberg F. Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles. IEEE Trans Ultrason Ferroelectr Freq Control. 2011 Oct;58(10):2056-66. doi: 10.1109/TUFFC.2011.2056.

  PMID: 21989870 BACKGROUND

• Dave JK, Halldorsdottir VG, Eisenbrey JR, Forsberg F. Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures. Ultrason Imaging. 2012 Apr;34(2):81-92. doi: 10.1177/016173461203400202.

  PMID: 22724314 BACKGROUND

• Dave JK, Halldorsdottir VG, Eisenbrey JR, Merton DA, Liu JB, Machado P, Zhao H, Park S, Dianis S, Chalek CL, Thomenius KE, Brown DB, Forsberg F. On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation. Ultrasonics. 2013 Apr;53(4):880-8. doi: 10.1016/j.ultras.2012.12.010. Epub 2013 Jan 2.

  PMID: 23347593 BACKGROUND

• Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures. Am J Physiol Heart Circ Physiol. 2012 Jul;303(1):H126-32. doi: 10.1152/ajpheart.00560.2011. Epub 2012 May 4.

  PMID: 22561300 BACKGROUND

• Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC Cardiovasc Imaging. 2012 Jan;5(1):87-92. doi: 10.1016/j.jcmg.2011.08.017.

  PMID: 22239898 BACKGROUND

• Eisenbrey JR, Dave JK, Halldorsdottir VG, Merton DA, Miller C, Gonzalez JM, Machado P, Park S, Dianis S, Chalek CL, Kim CE, Baliff JP, Thomenius KE, Brown DB, Navarro V, Forsberg F. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013 Aug;268(2):581-8. doi: 10.1148/radiol.13121769. Epub 2013 Mar 22.

  PMID: 23525208 BACKGROUND

• Forsberg F, Liu JB, Shi WT, Furuse J, Shimizu M, Goldberg BB. In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept. IEEE Trans Ultrason Ferroelectr Freq Control. 2005 Apr;52(4):581-3. doi: 10.1109/tuffc.2005.1428040.

  PMID: 16060506 BACKGROUND

• Halldorsdottir VG, Dave JK, Leodore LM, Eisenbrey JR, Park S, Hall AL, Thomenius K, Forsberg F. Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions. Ultrason Imaging. 2011 Jul;33(3):153-64. doi: 10.1177/016173461103300301.

  PMID: 21842580 BACKGROUND

• Shi WT, Forsberg F, Raichlen JS, Needleman L, Goldberg BB. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol. 1999 Feb;25(2):275-83. doi: 10.1016/s0301-5629(98)00163-x.

  PMID: 10320317 BACKGROUND

• Halldorsdottir VG, Dave JK, Eisenbrey JR, Machado P, Zhao H, Liu JB, Merton DA, Forsberg F. Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours--in vitro and in vivo proof of concept. Ultrasonics. 2014 Sep;54(7):1938-44. doi: 10.1016/j.ultras.2014.04.022. Epub 2014 May 6.

  PMID: 24856899 BACKGROUND

• Esposito C, Machado P, McDonald ME, Savage MP, Fischman D, Mehrotra P, Cohen IS, Ruggiero N 2nd, Walinsky P, Vishnevsky A, Dickie K, Davis M, Forsberg F, Dave JK. Noninvasive Evaluation of Cardiac Chamber Pressures Using Subharmonic-Aided Pressure Estimation With Definity Microbubbles. JACC Cardiovasc Imaging. 2023 Feb;16(2):224-235. doi: 10.1016/j.jcmg.2022.09.013. Epub 2022 Nov 16.

  PMID: 36648035 DERIVED

• Esposito C, Machado P, Cohen IS, Mehrotra P, Savage M, Fischman D, Davis M, Ruggiero N, Walinsky P, McDonald ME, Dickie K, Forsberg F, Dave JK. Comparing Central Aortic Pressures Obtained Using a SphygmoCor Device to Pressures Obtained Using a Pressure Catheter. Am J Hypertens. 2022 May 10;35(5):397-406. doi: 10.1093/ajh/hpac010.

  PMID: 35079778 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

perflutren

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Jaydev Dave

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 9, 2017
• Study Start: June 1, 2017
• Primary Completion: June 26, 2019
• Study Completion: June 26, 2019
• Last Updated: July 10, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: 2019-05-30 (anticipated) or starting 6 months after publication
• Access Criteria: Accessible research platform

Locations

US (1)