Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Nov 16;78(20):1990-2000.
doi: 10.1016/j.jacc.2021.08.068.

Echocardiographic Ischemic Memory Molecular Imaging for Point-of-Care Detection of Myocardial Ischemia

Brian P Davidson  1 , James Hodovan  1 , Michael E Layoun  2 , Harsh Golwala  1 , Firas Zahr  1 , Jonathan R Lindner  3
Affiliations
Clinical Trial

Echocardiographic Ischemic Memory Molecular Imaging for Point-of-Care Detection of Myocardial Ischemia

Brian P Davidson et al. J Am Coll Cardiol. .

Abstract

Background: Noninvasive molecular imaging of recent ischemia can potentially be used to diagnose acute coronary syndrome (ACS) with high accuracy.

Objectives: The authors hypothesized that bedside myocardial contrast echocardiography (MCE) ischemic memory imaging could be achieved with phosphatidylserine microbubbles (MBPS) that are retained in the microcirculation via ischemia-associated endothelial activation.

Methods: A dose-finding study was performed in healthy volunteers (n = 17) to establish optimal MBPS dosing. Stable patients with ACS (n = 30) and confirmed antecedent but resolved myocardial ischemia were studied within 2 hours of coronary angiography and percutaneous coronary intervention (PCI) when indicated. MCE molecular imaging was performed 8 minutes after intravenous administration of MBPS. MCE perfusion imaging was used to assess the status of the postischemic microcirculation.

Results: Based on dose-finding studies, 0.10 or 0.15 mL of MBPS based on body mass was selected. In patients with ACS, all but 2 underwent primary PCI. MCE molecular imaging signal intensity was greater in the postischemic risk area vs remote territory (median [95% CI]: 56 [33-66] vs 8 [2-17] IU; P < 0.001) with a receiver-operating characteristic curve C-statistic of 0.94 to differentiate post-ischemic from remote territory. Molecular imaging signal in the risk area was not related to type of ACS (unstable angina: 3; non-ST-segment elevation myocardial infarction: 14; ST-segment elevation myocardial infarction: 13), peak troponin, time to PCI, post-PCI myocardial perfusion, GRACE (Global Registry of Acute Coronary Events) score, or HEART score.

Conclusions: Molecular imaging with point-of-care echocardiography and MBPS can detect recent but resolved myocardial ischemia. This bedside technique requires only minutes to perform and appears independent of the degree of ischemia. (Ischemic Memory Imaging With Myocardial Contrast Echocardiography; NCT03009266).

Keywords: echocardiography; ischemia; molecular imaging.

PubMed Disclaimer

Conflict of interest statement

Funding Support and Author Disclosures This work was supported by a grant and material support from GE Healthcare. Dr Lindner is supported by grants R01-HL078610, R01-HL130046, and P51-OD011092 from the National Institutes of Health, Bethesda, Maryland, and by grant 18-18HCFBP_2-0009 from NASA, Washington, DC. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.. Imaging Algorithm and Dose-finding Studies.
(A) Kinetic model for molecular imaging whereby total myocardial concentration of MBPS (CM) represents the sum of retained (RM) and freely circulating (f) agent (see text). Graphs depict mean (±SEM) myocardial signal from (B) freely circulating; or (C) retained MBPS. (D) End-systolic apical 4-chamber (top) and 2-chamber (bottom) MCE images (0.6 mL dose) illustrating myocardial enhancement pre-flash and late post-flash. Apical enhancement is absent in the 2-chamber view (arrow) from previous 4-chamber flash. (E) Parasternal short-axis MCE illustrating myocardial signal enhancement from retained agent (1.2 mL dose), and signal voids from previous cavitation of agent in the three apical planes as labeled.
Figure 2.
Figure 2.. MCE Perfusion Imaging in ACS Subjects.
(A, B) Example of MCE perfusion images (3-chamber view) and corresponding time-intensity data illustrating complete reflow in the post-ischemic risk area in a patient 1–2 hours after PCI of the LAD. Background-subtracted color-coded (scale at right) end-systolic images are shown immediately after the cavitating flash sequence (BL) and at incremental end-systolic time intervals. Graphs depict MCE-derived (C) myocardial blood flow (MBF), and (D) microvascular blood volume index (MBVi) in the risk area and remote myocardium. Bar-and-whisker plots show median (bar), interquartile range (box), and range (whiskers).
Figure 3.
Figure 3.. MCE Ischemic Memory Molecular Imaging Signal by ACS Type and Vessel.
Box-whisker plots depicting MBPS signal in the risk area according to (A) type of ACS, and (B) culprit coronary artery territory. Examples show similar degrees of MBPS signal enhancement on MCE molecular imaging for two patients after PCI of the RCA for either (C) inferior NSTEMI, or (D) inferior STEMI. Images include grayscale MCE in the apical 2-chamber view obtained pre- and post-high-power flash sequence, and corresponding color-coded (scale at right) background-subtracted image. NSTEMI, non-ST-elevation MI; STEMI, ST-elevation MI; USAP, unstable angina pectoris.
Figure 4.
Figure 4.. Clinical Determinants of Ischemic Memory Molecular Imaging Signal Intensity.
Correlations are shown between the MCE molecular imaging signal for MBPS in the risk area and: (A) risk area myocardial blood flow (MBF); (B) Peak troponin-I; (C) time from symptom onset to percutaneous coronary intervention (PCI); (D) global longitudinal strain; and (E) GRACE score. Shaded regions depict 95% confidence interval of the regression line. (F) Box-whisker plot illustrates the MCE molecular imaging signal in the risk area and HEART score.
Central Illustration.
Central Illustration.. MCE Ischemic Memory Molecular Imaging in ACS Subjects.
(A) Apical 3-chamber MCE perfusion imaging late after flash-replenishment which represents microvascular reflow in the adjudicated LAD risk area (RA). (B) Grayscale MCE molecular imaging showing enhancement in the risk area, confirmed to be from MBPS retention by lack of reflow after the flash sequence. (C) Color-coded (scale at right) MCE molecular imaging derived by digital subtraction of freely circulating (post-flash) frames from pre-flash frames. Box-whisker plots illustrate (D) background-subtracted MBPS signal in the risk area and remote territory; and (E) signal normalized to MBF. (F) Receiver operating characteristic (ROC) curve for background-subtracted MBPS signal intensity to differentiate post-ischemic remote territory.
See this image and copyright information in PMC

Comment in

References

    1. Sandoval Y, Apple FS, Smith SW. High-sensitivity cardiac troponin assays and unstable angina. Eur Heart J Acute Cardiovasc Care 2018;7:120–128. - PubMed
    1. Forman DE, de Lemos JA, Shaw LJ et al. Cardiovascular Biomarkers and Imaging in Older Adults: JACC Council Perspectives. J Am Coll Cardiol 2020;76:1577–1594. - PMC - PubMed
    1. Lindner JR, Sinusas A. Molecular imaging in cardiovascular disease: Which methods, which diseases? J Nucl Cardiol 2013;20:990–1001. - PMC - PubMed
    1. Taegtmeyer H, Dilsizian V. Imaging myocardial metabolism and ischemic memory. Nat Clin Pract Cardiovasc Med 2008;5 Suppl 2:S42–8. - PubMed
    1. Kontos MC, Dilsizian V, Weiland F et al. Iodofiltic acid I 123 (BMIPP) fatty acid imaging improves initial diagnosis in emergency department patients with suspected acute coronary syndromes: a multicenter trial. J Am Coll Cardiol 2010;56:290–9. - PubMed

Publication types

MeSH terms

Associated data