3D ultrasound coronarography: first proof of concept study on isolated beating rat hearts

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Bettencourt Foundation Background/Introduction We demonstrated recently that Ultrafast ultrasound Doppler imaging can image the intramyocardial coronary circulation in beating hearts of large animals and patients [1]. Yet, ultrasound spatial resolution remains limited by wave physics and coronaries smaller than ∼100 µm could not be imaged. Ultrasound Localization Microscopy (ULM) [2] was recently introduced to tackle this issue and exploit the micrometric localization of microbubble contrast agents at ultrafast frame rate in order to image blood flows in micrometer vessels. Purpose The objective of this work was to demonstrate that 3D ultrafast ultrasound with contrast agents can provide the full 3D mapping of the coronary microcirculation with quantitative flow velocity on a beating rat heart. Methods Acquisitions were performed on ex vivo rat hearts (n = 5) with retrograde perfusion (Langendorff model). A flow of a Krebs–Henseleit solution mixed with a diluted microbubbles solution (0.22%) was perfused at controlled pressure into the coronary arteries (between 5 and 15 mL/min). We used a 32 × 32 elements, 8-MHz matrix-array ultrasound transducer connected to a 1024-channel programmable ultrasound scanner. An ultrafast Doppler imaging sequence consisting of 9 plane waves was transmitted at a PRF of 20 kHz during 270 ms and repeated 40 times. After beamforming and SVD clutter filtering, the microbubbles were localized and tracked in 3D. Flow velocity were mapped at baseline and after infusion of Adenosine (10e-5 µMol) at constant coronary perfusion pressure (120 mm Hg). Eventually, the hearts were fixed using formaldehyde perfusion and imaged by µCT after injection of radio opaque agent. Results We successfully imaged the coronary blood flows of entire rat hearts. It revealed the entire vasculature from large main coronaries arteries (cross section up to 1 mm) to small arterioles (smaller than 40 µm). Coronary flow velocities ranged from [1 – 50] cm/s depending on the arteries diameter. Velocity estimates were validated in vitro in tubes of Ø0.58mm and were in good agreement with theoretical values of a Poiseuille’s flow (relative ratio of 10% for maximum velocities). After Adenosine infusion, perfusion flow rates increased 102% ± 50% (p < 0.05) on average. Eventually, anatomy revealed by 3D ultrasound coronarography was in accordance with the anatomy revealed by the µCT. Conclusion(s) We demonstrated the feasibility of 3D ultrasound coronarography on isolated beating rat hearts. This technique has the potential to become a novel imaging tool to investigate the coronary micro-circulation and quantify non-invasively the Coronary Flow Reserve (CFR). Abstract Figure. Ultrasound coronarography

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Abstract 19177: Loss of Coronary Perfusion Efficiency in Microvascular Disease

Circulation ◽

10.1161/circ.132.suppl_3.19177 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Matthew Lumley ◽

Matthew Ryan ◽

Kaleab Asrress ◽

Rupert Williams ◽

Satpal Ari ◽

...

Keyword(s):

Flow Velocity ◽

Coronary Flow ◽

Microvascular Disease ◽

Rate Pressure Product ◽

Coronary Perfusion ◽

Cardiac Events ◽

Fractional Flow ◽

Wave Separation ◽

Flow Reserve ◽

Response To Stress

Introduction: Coronary Microvascular Disease (MVD) is associated with an unfavorable prognosis, even in the absence of significant epicardial disease. The pathophysiological basis of increased cardiac events is unclear. The aim of this study was to characterize the forces that govern myocardial perfusion at rest and during stress. Methods: Patients with chest pain syndromes requiring Fractional Flow Reserve (FFR) assessment were screened and those with a FFR>0.80 were included. MVD was defined by coronary flow reserve (CFR) < 2.0. Controls were those with CFR>2.0. Simultaneous intracoronary pressure (P d ) and flow velocity (U) recordings were made at rest and hyperemia. Microvascular Resistance (MR)= P d /U. Wave intensity = dP d /dt x dU/dt and wave separation analysis was used to identify the waves that accelerate and decelerate flow. The proportional contribution of accelerating waves was assessed as an index of coronary perfusion efficiency. Results: 39 consecutive patients were enrolled, 21 had MVD and 18 comprised controls. The groups were matched for atherosclerotic risk factors, rate-pressure-product and P d . Coronary flow velocity in MVD patients was higher at rest (21.5±6.4 vs. 14.1±4.5cms -1 , p < 0.001) but lower during hyperemia (28.3±13.0 vs. 45.1±13.1cms -1 , p < 0.001) compared to controls. While resting MR was lower in MVD (501±162 vs. 755±262 mmHg.cm -1 .s, p = 0.001), hyperemic MR was significantly lower in controls. At rest the magnitude of the accelerating waves was higher in the MVD group than controls. The percentage contribution of accelerating waves increased with hyperemia in controls but decreased in MVD patients (figure). Conclusion: MVD manifests as resting microvascular dilation as well as diminished response to stress. While the normal heart has improved efficiency during hyperemia, in MVD efficiency decreases and as a result, flow augmentation is attenuated. These processes render the myocardium more susceptible to ischemia.

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Relationship between coronary flow velocity reserve and aortic stiffness

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01187.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. H1311-H1311 ◽

Cited By ~ 8

Author(s):

A. Nemes ◽

Tamás Forster ◽

Miklós Csanády

Keyword(s):

Flow Velocity ◽

Coronary Flow ◽

Aortic Stiffness ◽

Coronary Intervention ◽

Doppler Velocity ◽

Coronary Perfusion ◽

Coronary Flow Velocity Reserve ◽

Fractional Flow ◽

Coronary Flow Velocity ◽

Flow Reserve

We examined the hypothesis that a stiff aorta is associated with reduced coronary blood flow (CBF) and CBF response to percutaneous coronary intervention (PCI). Aortic mechanical properties are thought to affect CBF, with increased stiffness associated with decreased coronary perfusion. Animal studies are conflicting, and human evidence is lacking. Even less is known about the effects of aortic stiffness on the CBF response to successful PCI. In 18 subjects undergoing elective PCI, a Doppler velocity guidewire was positioned proximal to a severe coronary stenosis to measure resting and adenosine-induced hyperemic CBF before and after PCI. Stenosis severity was assessed with Doppler velocity and pressure guidewires. Aortic mechanical indexes measured included central pulse-wave velocity (cPWV) and central pulse pressure (cPP). PCI was successful in all subjects (diameter stenosis: 88 ± 9% to 2 ± 7%; coronary flow velocity reserve: 1.8 ± 0.6 to 3.0 ± 0.8; fractional flow reserve: 0.57 ± 0.19 to 0.92 ± 0.06; all P < 0.001). With the adjustment for age and gender, resting and hyperemic CBF were inversely related to cPWV irrespective of the presence of stenosis (resting: before PCI, r2 = 0.452, P < 0.01; after PCI, r2 = 0.261, P = 0.043; hyperemic: before PCI r2 = 0.503, P = 0.005; after PCI r2 = 0.500, P = 0.002), whereas they were related to cPP in absence of stenosis (resting: r2 = 0.368, P = 0.022; hyperemic: r2 = 0.370, P = 0.016). Hyperemic CBF response ( P = 0.005) and hyperemic CBF improvement from PCI ( P = 0.025) were less marked in a stiff aorta than a compliant aorta. A stiff aorta is associated with a reduction in CBF, a lower hyperemic CBF response, and may reduce the improvement in hyperemic CBF after successful PCI.

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Coronary Flow and Reserve by Enhanced Transthoracic Doppler Trumps Coronary Anatomy by Computed Tomography in Assessing Coronary Artery Stenosis

Diagnostics ◽

10.3390/diagnostics11020245 ◽

2021 ◽

Vol 11 (2) ◽

pp. 245

Author(s):

Carlo Caiati ◽

Arnaldo Scardapane ◽

Fortunato Iacovelli ◽

Paolo Pollice ◽

Teresa Immacolata Achille ◽

...

Keyword(s):

Coronary Artery ◽

Coronary Angiography ◽

Flow Velocity ◽

Coronary Flow ◽

Invasive Coronary Angiography ◽

Coronary Anatomy ◽

Color Mapping ◽

Flow Reserve ◽

Mild Stenosis ◽

Iodinated Contrast

We report the case of a 71-year-old patient with many risk factors for coronary atherosclerosis, who underwent computed coronary angiography (CTA), in accordance with the guidelines, for recent onset atypical chest pain. CTA revealed critical (>50% lumen diameter narrowing) stenosis of the proximal anterior descending coronary, and the patient was scheduled for invasive coronary angiography (ICA). Before ICA he underwent enhanced transthoracic echo-Doppler (E-Doppler TTE) for coronary flow detection by color-guided pulsed-wave Doppler recording of the left main (LMCA) and whole left anterior descending coronary artery (LAD,) along with coronary flow reserve (CFR) in the distal LAD calculated as the ratio, of peak flow velocity during i.v. adenosine (140 mcg/Kg/m) to resting flow velocity. E-Doppler TTE mapping revealed only mild stenosis (28% area narrowing) of the mid LAD and a CFR of 3.20, in perfect agreement with the color mapping showing no flow limiting stenosis in the LMCA and LAD. ICA revealed only a very mild stenosis in the mid LAD and mild atherosclerosis in the other coronaries (intimal irregularities). Thus, coronary stenosis was better predicted by E-Doppler TTE than by CTA. Coronary flow and reserve as assessed by E-Doppler TTE trumps coronary anatomy as assessed by CTA, without exposing the patient to harmful radiation and iodinated contrast medium.

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Abstract 14743: Usefulness of Estimated Coronary Flow Velocity Using Quantitative Flow Ratio for Intermediate Coronary Stenosis

Circulation ◽

10.1161/circ.142.suppl_3.14743 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Eiji Ichimoto ◽

Nao Konagai ◽

Sawako Horie ◽

Atsushi Hasegawa ◽

Hirofumi Miyahara ◽

...

Keyword(s):

Flow Velocity ◽

Coronary Stenosis ◽

Coronary Flow ◽

Flow Ratio ◽

Operating Characteristics ◽

Fractional Flow ◽

Coronary Flow Velocity ◽

Flow Reserve ◽

Quantitative Flow Ratio ◽

Quantitative Flow

Introduction: Quantitative flow ratio (QFR) is a diagnostic modality for functional assessment for intermediate coronary stenosis without the use of pressure wire. QFR is calculated from 3-dimensional quantitative CAG (3D-QCA) using an advanced algorithm that enables fast computation of the pressure drop caused by coronary stenosis. Hypothesis: We assessed the usefulness of QFR and the association with an estimated coronary flow velocity (eCFV) for intermediate coronary stenosis. Methods: A total of 100 lesions in 80 consecutive patients were assessed Fractional Flow Reserve (FFR) for intermediate coronary stenosis between January 2011 and April 2019. Of these, 97 lesions in 77 patients who underwent QFR were included in this study. Patients were classified into two groups (FFR ≤ 0.80 or FFR > 0.80). QFR and eCFV using contrast were measured by Thrombolysis in Myocardial Infarction (TIMI) frame counts. Results: There was no significant differences in target vessels (p = 0.90) and diffuse lesions (p = 0.06) between the two groups (FFR ≤ 0.80 or FFR > 0.80). Mean FFR and QFR values were 0.78 ± 0.12 and 0.77 ± 0.11, respectively. QFR had a good correlation with FFR values (r = 0.86, p < 0.0001). The diagnostic accuracy, sensitivity, and specificity on QFR ≤ 0.80 were 91.8%, 92.7% and 90.5%, respectively. The eCFV of FFR ≤ 0.80 was greater than that of FFR > 0.80 (0.19 ± 0.08 m/s vs. 0.14 ± 0.06 m/s, p<0.001). Figure showed that the eCFV correlated with FFR values (r = -0.29, p < 0.01). Moreover, the eCFV had a high area under the curve (AUC = 0.71, p < 0.01) on Receiver operating characteristics curve (ROC) analysis with FFR ≤ 0.80. Conclusions: QFR was useful for the assessment of functional stenosis severity. As eCFV was faster, FFR was lower for intermediate coronary stenosis. The eCFV had a good correlation with FFR and may become one of the evaluations for ischemia.

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How Do Fractional Flow Reserve, Whole-Cycle PdPa, and Instantaneous Wave-Free Ratio Correlate With Exercise Coronary Flow Velocity During Exercise-Induced Angina?

Circulation Cardiovascular Interventions ◽

10.1161/circinterventions.119.008460 ◽

2020 ◽

Vol 13 (4) ◽

Author(s):

Christopher M. Cook ◽

James P. Howard ◽

Yousif Ahmad ◽

Matthew J. Shun-Shin ◽

Amarjit Sethi ◽

...

Keyword(s):

Flow Velocity ◽

Fractional Flow Reserve ◽

Coronary Flow ◽

Fractional Flow ◽

Coronary Flow Velocity ◽

Flow Reserve ◽

Exercise Induced

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Impairment of coronary flow reserve in aortic stenosis

Journal of Applied Physiology ◽

10.1152/japplphysiol.00049.2008 ◽

2009 ◽

Vol 106 (1) ◽

pp. 113-121 ◽

Cited By ~ 69

Author(s):

Damien Garcia ◽

Paolo G. Camici ◽

Louis-Gilles Durand ◽

Kim Rajappan ◽

Emmanuel Gaillard ◽

...

Keyword(s):

Coronary Flow Reserve ◽

Coronary Flow ◽

Left Ventricular ◽

Adverse Outcomes ◽

Lumped Parameter Model ◽

Effective Orifice Area ◽

Sensitivity Index ◽

Coronary Perfusion ◽

Flow Reserve ◽

Wide Range

Coronary flow reserve (CFR) is markedly reduced in patients with severe aortic valve stenosis (AS), but the exact mechanisms underlying this impairment of CFR in AS remain unclear. Reduced CFR is the key mechanism leading to myocardial ischemia symptoms and adverse outcomes in AS patients. The objective of this study was to develop an explicit mathematical model formulated with a limited number of parameters that describes the effect of AS on left coronary inflow patterns and CFR. We combined the mathematical V3 (ventricular-valvular-vascular) model with a new lumped-parameter model of coronary inflow. One thousand Monte-Carlo computational simulations with AS graded from mild up to very severe were performed within a wide range of physiological conditions. There was a good agreement between the CFR values computed with this new model and those measured in 24 patients with isolated AS ( r = 0.77, P < 10−4). A global sensitivity analysis showed that the valve effective orifice area (EOA) was the major physiological determinant of CFR (total sensitivity index = 0.87). CFR was markedly reduced when AS became severe, i.e., when EOA was <1.0 cm2, and was generally exhausted when the EOA was <0.5–0.6 cm2. The reduction of CFR that is associated with AS can be explained by the concomitance of 1) reduced myocardial supply as a result of decreased coronary perfusion pressure, and 2) increased myocardial metabolic demand as a result of increased left ventricular workload.

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