Volumetric coronary endothelial function assessment: a feasibility study exploiting stack-of-stars 3D cine MRI and image-based respiratory self-gating.

Abnormal coronary endothelial function (CEF), manifesting as depressed vasoreactive responses to endothelial-specific stressors, occurs early in atherosclerosis, independently predicts cardiovascular events, and responds to cardioprotective interventions. CEF is spatially heterogeneous along a coronary artery in patients with atherosclerosis, and thus recently developed and tested non-invasive 2D MRI techniques to measure CEF may not capture the extent of changes in CEF in a given coronary artery. The purpose of this study was to develop and test the first volumetric coronary 3D MRI cine method for assessing CEF along the proximal and mid-coronary arteries with isotropic spatial resolution and in free-breathing. This approach, called 3D-Stars, combines a 6 min continuous, untriggered golden-angle stack-of-stars acquisition with a novel image-based respiratory self-gating method and cardiac and respiratory motion-resolved reconstruction. The proposed respiratory self-gating method agreed well with respiratory bellows and center-of-k-space methods. In healthy subjects, 3D-Stars vessel sharpness was non-significantly different from that by conventional 2D radial in proximal segments, albeit lower in mid-portions. Importantly, 3D-Stars detected normal vasodilatation of the right coronary artery in response to endothelial-dependent isometric handgrip stress in healthy subjects. Coronary artery cross-sectional areas measured using 3D-Stars were similar to those from 2D radial MRI when similar thresholding was used. In conclusion, 3D-Stars offers good image quality and shows feasibility for non-invasively studying vasoreactivity-related lumen area changes along the proximal coronary artery in 3D during free-breathing.

Validation of Wall Shear Stress Assessment in Non-invasive Coronary CTA versus Invasive Imaging: A Patient-Specific Computational Study.

Endothelial shear stress (ESS) identifies coronary plaques at high risk for progression and/or rupture leading to a future acute coronary syndrome. In this study an optimized methodology was developed to derive ESS, pressure drop and oscillatory shear index using computational fluid dynamics (CFD) in 3D models of coronary arteries derived from non-invasive coronary computed tomography angiography (CTA). These CTA-based ESS calculations were compared to the ESS calculations using the gold standard with fusion of invasive imaging and CTA. In 14 patients paired patient-specific CFD models based on invasive and non-invasive imaging of the left anterior descending (LAD) coronary arteries were created. Ten patients were used to optimize the methodology, and four patients to test this methodology. Time-averaged ESS (TAESS) was calculated for both coronary models applying patient-specific physiological data available at the time of imaging. For data analysis, each 3D reconstructed coronary artery was divided into 2 mm segments and each segment was subdivided into 8 arcs (45°).TAESS and other hemodynamic parameters were averaged per segment as well as per arc. Furthermore, the paired segment- and arc-averaged TAESS were categorized into patient-specific tertiles (low, medium and high). In the ten LADs, used for optimization of the methodology, we found high correlations between invasively-derived and non-invasively-derived TAESS averaged over segments (n = 263, r = 0.86) as well as arcs (n = 2104, r = 0.85, p < 0.001). The correlation was also strong in the four testing-patients with r = 0.95 (n = 117 segments, p = 0.001) and r = 0.93 (n = 936 arcs, p = 0.001).There was an overall high concordance of 78% of the three TAESS categories comparing both methodologies using the segment- and 76% for the arc-averages in the first ten patients. This concordance was lower in the four testing patients (64 and 64% in segment- and arc-averaged TAESS). Although the correlation and concordance were high for both patient groups, the absolute TAESS values averaged per segment and arc were overestimated using non-invasive vs. invasive imaging [testing patients: TAESS segment: 30.1(17.1-83.8) vs. 15.8(8.8-63.4) and TAESS arc: 29.4(16.2-74.7) vs 15.0(8.9-57.4) p < 0.001]. We showed that our methodology can accurately assess the TAESS distribution non-invasively from CTA and demonstrated a good correlation with TAESS calculated using IVUS/OCT 3D reconstructed models.

High dose escalation of intracoronary adenosine in the assessment of fractional flow reserve: A retrospective cohort study.

Maximal hyperaemia for fractional flow reserve (FFR) may not be achieved with the current recommended doses of intracoronary adenosine. Higher doses (up to 720 µg) have been reported to optimize hyperaemic stimuli in small dose-response studies. Real-world data from a large cohort of patients is needed to evaluate FFR results and the safety of high-dose escalation. This is a retrospective study aimed to evaluate the safety and frequency of FFR ≤0.8 after high-dose escalation of intracoronary adenosine. Data were extracted from the medical databases of two university hospitals. Increasing doses (100, 200, 400, 600, and 800 µg) of adenosine were administered as intracoronary boluses until FFR ≤0.8 was achieved or heart block developed. The percentage of FFR ≤0.8 after higher-dose escalation was compared with those at conventional doses, and the predictors for FFR ≤0.8 after higher doses were analysed. In the 1163 vessels of 878 patients, 402 vessels (34.6%) achieved FFR ≤0.8 at conventional doses and 623 vessels (53.6%) received high-dose escalation. An additional 84 vessels (13.5%) achieved FFR ≤0.8 after high-dose escalation. No major complications developed during high-dose escalation. Borderline FFR (0.81-0.85) at the conventional dose, stenosis >60%, and triple-vessel disease increased the likelihood of FFR ≤0.8 after high-dose escalation, but chronic kidney disease decreased it. For vessels of borderline FFR at conventional doses, 46% achieved FFR ≤0.8 after high-dose escalation. In conclusion, High-dose escalation of intracoronary adenosine increases the frequency of FFR ≤0.8 without major complications. It could be especially feasible for borderline FFR values near the 0.8 diagnostic threshold.

An intact animal model for the assessment of coronary blood flow regulation "Coronary blood flow regulation".

Coronary blood flow adapts to metabolic demand ("metabolic regulation") and remains relatively constant over a range of pressure changes ("autoregulation"). Coronary metabolic regulation and autoregulation are usually studied separately. We developed an intact animal experimental model to explore both regulatory mechanisms of coronary blood flow. Coronary pressure and flow-velocities were measured in four anesthetized and closed-chest pigs using an intracoronary Doppler wire. Metabolic regulation was assessed by coronary flow reserve defined as the ratio between the maximally vasodilated and the basal flow, with hyperemia achieved using intracoronary administration of adenosine (90 µg) or bradykinin (10-6  M) as endothelium-independent and -dependent vasodilators respectively. For both vasodilators, we found a healthy coronary flow reserve ≥ 3.0 at baseline, which was maintained at 2.9 ± 0.2 after a 6-hr period. Autoregulation was assessed by the lower breakpoint of coronary pressure-flow relationships, with gradual decrease in coronary pressure through the inflation of an intracoronary balloon. We found a lower limit of autoregulation between 42 and 55 mmHg, which was stable during a 6-hr period. We conclude that this intact animal model is adequate for the study of pharmacological interventions on the coronary circulation in health and disease, and as such suitable for preclinical drug studies.

Comprehensive assessment of coronary pulse wave velocity in anesthetized pigs.

BACKGROUND: Coronary stiffness represents a new paradigm for interventional cardiology and can be assessed by coronary pulse wave velocity (CoPWV). Assessing CoPWV is complex because of the coexistence of backward and forward waves. OBJECTIVES: Evaluate the feasibility, repeatability, and capacity of methods assessing CoPWV to detect predictable velocity changes. METHODS: CoPWV was measured from distal and proximal pressure guidewires in the left anterior descending artery of 10 pigs under general anesthesia. Four methods were studied: the tangent intersection method applied to the forward (FW) and backward (BK) waves, as well as the dicrotic notch (DIC) and template matching (TM) methods. All were evaluated at baseline, during various arterial pressure and heart rate conditions, during simulated flow limitation (balloon inflation), and after increasing coronary stiffness (stent insertion). RESULTS: All the methods were significantly different between them (p ≤ .05) showing a systematic trend toward higher CoPWV when compared to the FW method (.05 < p<.10). Results were found to be significantly correlated only between the BK and FW methods and between the DIC and TM methods (p ≤ .05). CoPWV increased with arterial pressure increase, this increase being significant for the DIC and TM methods and partly for the FW method (p ≤ .05). Conversely, heart rate had no systematic impact on CoPWV. The lowest variability was found for the DIC and TM methods (p ≤ .05). Only the BK and TM methods remained applicable during flow limitation; stent increased CoPWV when measured by the BK method only (p ≤ .05). CONCLUSION: Although CoPWV can be measured by various methods, the BK and TM methods seem the most appropriate for clinical studies.

Feasibility of coronary endothelial function assessment using arterial spin labeled CMR.

Coronary endothelial dysfunction (CED) is an independent predictor of cardiovascular disease, but its assessment has been limited to invasive coronary angiography. Myocardial perfusion imaging using arterial spin labeled (ASL) cardiac magnetic resonance (CMR) may be an effective non-invasive alternative for detection of CED. Thirty-four patients were recruited: 10 healthy volunteers, 13 at high-risk for coronary artery disease (CAD), and 11 with established CAD. ASL-CMR was performed continuously in a single mid-short axis slice during rest, stress, and recovery. Stress was induced with sustained isometric handgrip exercise, an endothelial dependent stressor. Myocardial perfusion (MP) during rest, peak stress, and recovery were calculated and compared. After excluding subjects unable to complete the protocol or who exhibited poor data quality, 6 healthy, 10 high-risk, and 7 CAD patients were included in the analysis. Average MP (ml/g/min) was 1.31 ± 1.23, 1.61 ± 1.12, and 1.40 ± 0.97 at rest, and 1.64 ± 1.49, 2.31 ± 1.61, and 2.84 ± 1.77 during stress, for the CAD, high-risk and healthy group, respectively. The average MP response (MPstress - MPrest , ml/g/min) was 0.32 ± 1.93, 0.69 ± 1.34, and 1.44 ± 1.46 for CAD, high-risk and healthy group, respectively. MP during handgrip stress was significantly lower for both the CAD (p = 0.0005) and high-risk groups (p = 0.05) compared to the healthy volunteers. In only the healthy subjects, MP was significantly higher in stress compared to rest (p = 0.0002). Participants with CAD had significantly lower MP response compared to healthy volunteers, as detected by ASL-CMR. These findings support the feasibility of ASL-CMR for non-invasive assessment of CED.

Influence of residual coronary flow on bypass graft flow for graft assessment using near-infrared fluorescence angiography.

PURPOSE: Near-infrared fluorescence angiography (NIR) detects the attenuation of fluorescence luminance intensity (FLI) through coronary artery bypass grafts affected by anastomotic stenosis. This study investigates the influence of residual blood flow of the host coronary artery (Ho) on bypass graft (Gr) FLI using a coronary artery bypass (CABG) model. METHODS: A mock circuit system was created using artificial vessels and artificial blood was supplied to the Gr and the Ho. We used NIR to examine the changes in FLI through the Gr. RESULTS: The Gr FLI was significantly attenuated according to the degree of Gr stenosis. The Gr FLI did not differ significantly among all degrees of Ho stenosis. High FLI grafts included grafts with degrees of Gr stenosis ≤ 75%, regardless of the severity of Ho stenosis. Moderate and low FLI grafts had 90 or 99% Gr stenosis, regardless of the severity of Ho stenosis. Gr FLI with 99% Gr stenosis was higher in 99% Ho stenosis than in ≤ 90% Ho stenosis. CONCLUSIONS: A high Gr FLI indicated the absence of ≥ 90% stenosis in the anastomosis and a low Gr FLI indicated severe stenosis in the anastomosis despite Ho stenosis. High Ho stenosis may prevent the attenuation of Gr FLI in severely stenosed grafts.

Assessment of coronary physiology - the evidence and implications.

Use of angiography for the assessment of coronary lesions is limited by its inability to provide information regarding the functional significance of stenoses. A number of studies have demonstrated the presence of ischaemia to be the most important determinant of the benefit associated with coronary revascularisation in stable coronary artery disease. Assessment of intra-coronary physiology can guide percutaneous coronary intervention, and is often used for angiographically borderline stenoses. There is now increasing evidence to suggest that more routine use can improve clinical outcomes. Fractional flow reserve (FFR) is the most established measure of intra-coronary physiology, but is currently under-utilised. The main drawback of FFR is the dependence on a pharmacological infusion to maintain hyperaemia. An alternative technique which measures flow at a specific point in the cardiac cycle (instantaneous wave-free ratio) has been developed which obviates the need for hyperaemia and may replace FFR as the default measure.

Assessment with intracoronary pressure and flow guidewire, at baseline and after intracoronary adenosine infusion, in a patient with Takotsubo syndrome.

We present the case of a patient with Takotsubo syndrome assessed by intracoronary flow and pressure guidewire, showing elevation of intracoronary pressures at the level of the anterior descending artery, and thus demonstrating a new therapeutic target in a still little understood etiopathogenic entity. The results of this test have never been previously reported in Takotsubo patients.

Assessment of coronary vascular function with cardiac PET in relation to serum uric acid.

BACKGROUND: Elevated serum uric acid (SUA) levels have been independently associated with cardiovascular disease. Stress myocardial perfusion positron emission tomography (PET) allows for measurement of absolute myocardial blood flow (MBF) and quantification of global left ventricular coronary flow reserve (CFR). A CFR <2.0 is considered impaired coronary vascular function, and it is associated with increased cardiovascular risk. We evaluated the relationship between SUA and PET-measured markers of coronary vascular function. METHODS: We studied adults undergoing a stress myocardial perfusion PET on clinical grounds (1/2006-3/2014) who also had ≥1 SUA measurement within 180 days from the PET date. Multivariable linear regression estimated the association between SUA and PET-derived MBF and CFR. We also stratified analyses by diabetes status. RESULTS: We included 382 patients with mean (SD) age of 68.4 (12.4) years and mean (SD) SUA level of 7.2 (2.6) mg/dl. 36% were female and 29% had gout. Median [IQR] CFR was reduced at 1.6 [1.2, 2.0] and median [IQR] stress MBF was 1.5 [1.1, 2.1] ml/min/g. In the adjusted analysis, SUA was inversely associated with stress MBF (ß = -0.14, p = 0.01) but not with CFR. Among patients without diabetes (n = 215), SUA had a negative association with CFR (ß = -0.15, p = 0.02) and stress MBF (ß = -0.19, p = 0.01) adjusting for age, sex, extent of myocardial scar and ischemia, serum creatinine and gout. In diabetic patients (n = 167), SUA was not associated with either CFR or MBF. CONCLUSIONS: In this cross-sectional study, higher SUA is modestly associated with worse CFR and stress MBF among patients without diabetes.

Optimization of imaging protocols for myocardial blood flow (MBF) quantification with 18F-flurpiridaz PET.

The new PET tracer, 18F-flurpiridaz, with high myocardial extraction allows quantitative myocardial blood flow (MBF) estimation from dynamic PET data and tracer kinetic modeling. The goal of this study is to determine the optimal imaging protocols and parameters using a realistic simulation study. The time activity curves (TACs) of different tissue organs from a 30-s infusion time (IT) of 18F-flurpiridaz in a dynamic PET study were extracted from a previous study. The TACs at different time points were incorporated in a series of realistic 3D XCAT phantoms from which the parameters of a 2-compartment model and the 'true' MBF of 18F-flurpiridaz were determined. The compartmental model was used to generate TACs from 7 additional ITs. PET projection data from the XCAT phantoms were generated using Monte Carlo simulation. They were reconstructed using an OS-EM reconstruction algorithm with different update number (N) to obtain dynamic PET images. The blood and myocardial TACs were derived from the dynamic images from which the MBF and %MBF error was estimated. The %MBF error decreases with increasing N of the OS-EM and levels off after ∼42. The 30-s IT gave the smallest %MBF error that decreases from ∼0.57% to ∼19.40%. The MBF for 2-min, 4-min, 8-min and 16-min IT were statistically significant different from the MBF for 30-s IT (P<0.05). Too fast or too slow infusion time gave higher %MBF error. The optimal imaging protocol in dynamic 18F-flurpiridaz PET for accurate quantitative MBF estimation was 30-s IT and N of ∼42 for the OS-EM.

Assessment of vascular response to BiOSS LIM C® stents vs Orsiro® stents in the porcine coronary artery model.

AIMS: The optimal treatment strategy for coronary bifurcation lesions is still unknown. The aim of the study was to assess applicability of the new cobalt-chromium version of the sirolimus-eluting dedicated bifurcation BiOSS® LIM C stent in comparison with regular sirolimus-eluting Orsiro®  stent in a porcine coronary model. METHODS: A total of 13 BiOSS® LIM C stents and 6 Orsiro® stents were implanted in normal nonatherosclerotic porcine straight coronary arteries of six animals using 1.2:1.0 stent-to-artery ratio. Stent geometry and morphology were evaluated by Faxitron imaging. Vascular response was assessed by quantitative coronary angiography (QCA), optical coherence tomography (OCT), and histological analyses. RESULTS: OCT performed at 28 days confirmed that all stents were patent with no signs of thrombus. In morphometric analysis, no differences between groups regarding stent diameter (P=.141), neointima area (P=.247), % area stenosis (P=.293), or % diameter stenosis (P=.069) were observed. Also, no significant differences were noted between groups regarding their histopathology scores. The injury and inflammation scores were low (mean grade<1) in all groups. CONCLUSIONS: The novel BiOSS® LIM C stent demonstrates good short-term vascular effects in a porcine coronary bifurcation model which are comparable with Orsiro® stents.

Preserved autoregulation of coronary flow after off-pump coronary artery bypass grafting: retrospective assessment of intraoperative transit time flowmetry with and without intra-aortic balloon counterpulsation.

BACKGROUND: Intra-aortic balloon pumping (IABP) markedly increases graft flow after coronary artery bypass grafting (CABG) with cardiopulmonary bypass. We sought to delineate the effects of IABP on graft flow after off-pump CABG (OPCAB). METHODS: The clinical records of 32 patients (25 male, 7 female; mean age: 70 ± 9 years) who underwent OPCAB with IABP between January 2011 and May 2015 were retrospectively reviewed. Thirteen patients (41%) had a history of myocardial infarction, and 13 patients (41%) had a history of percutaneous coronary intervention. In total, there were 76 bypass grafts with 102 distal anastomoses. These included 50 in situ or pedicled grafts and 26 aortocoronary grafts. After completion of the anastomoses, the heart was positioned normally, and graft flow with IABP was measured using transit-time flowmetry under stable circulation. Then, IABP was turned off for 30 s to a few minutes, until graft flow was constant, for measurement of flow off IABP. RESULTS: The angiographic patency rate was 100% (47/47). Overall, graft flow was 55 ± 36 ml/min on IABP and 53 ± 36 ml/min off IABP (p = 0.37). The pulsatility index was 4.1 ± 2.1 on IABP and 2.7 ± 1.5 off IABP (p < 0.001). There was no significant difference in graft flow between on and off IABP for aortocoronary bypass or in situ grafts. Graft flow was 57 ± 36 ml/min on IABP and 55 ± 37 ml/min off IABP (p = 0.41) in in situ grafts and 52 ± 34 ml/min on IABP and 49 ± 35 off IABP (p = 0.41) in aortocoronary grafts. Graft flow on IABP was more than 5 ml/min greater in 28 (37%) bypass grafts, and more than 5 ml/min lower in 20 (26%) bypass grafts. CONCLUSION: In contrast to previous reports for conventional CABG, graft flow after OPCAB was not necessarily increased by IABP, regardless of elevated diastolic arterial pressure. It is suggested that preserved autoregulation of coronary flow contributes to a lower impact on the heart and early functional recovery, and consequently, greater perioperative safety of OPCAB.

The influence of elective percutaneous coronary intervention on microvascular resistance: a serial assessment using the index of microcirculatory resistance.

This study investigates whether hyperemic microvascular resistance (MR) is influenced by elective percutaneous coronary intervention (PCI) by using the index of microcirculatory resistance (IMR). Seventy-one consecutive patients with stable angina pectoris undergoing elective PCI were prospectively studied. The IMR was measured before and after PCI and at the 10-mo follow-up. The IMR significantly decreased until follow-up; the pre-PCI, post-PCI, and follow-up IMRs had a median of 19.8 (interquartile range, 14.6-28.9), 16.2 (11.8-22.1), and 14.8 (11.8-18.7), respectively (P < 0.001). The pre-PCI IMR was significantly correlated with the change in IMR between pre- and post-PCI (r = 0.84, P < 0.001) and between pre-PCI and follow-up (r = 0.93, P < 0.001). Pre-PCI IMR values were significantly higher in territories with decreases in IMR than in those with increases in IMR [pre-PCI IMR: 25.4 (18.4-35.5) vs. 12.5 (9.4-16.8), P < 0.001]. At follow-up, IMR values in territories showing decreases in IMR were significantly lower than those with increases in IMR [IMR at follow-up: 13.9 (10.9-17.6) vs. 16.6 (14.0-21.4), P = 0.013]. The IMR decrease was significantly associated with a greater shortening of mean transit time, indicating increases in coronary flow (P < 0.001). The optimal cut-off values of pre-PCI IMR to predict a decrease in IMR after PCI and at follow-up were 16.8 and 17.0, respectively. In conclusion, elective PCI affected hyperemic MR and its change was associated with pre-PCI MR, resulting in showing a wide distribution. Overall hyperemic MR significantly decreased until follow-up. The modified hyperemic MR introduced by PCI may affect post-PCI coronary flow.

Quantitative three-dimensional myocardial perfusion cardiovascular magnetic resonance with accurate two-dimensional arterial input function assessment.

BACKGROUND: Quantification of myocardial perfusion from first-pass cardiovascular magnetic resonance (CMR) images at high contrast agent (CA) dose requires separate acquisition of blood pool and myocardial tissue enhancement. In this study, a dual-sequence approach interleaving 2D imaging of the arterial input function with high-resolution 3D imaging for myocardial perfusion assessment is presented and validated for low and high CA dose. METHODS: A dual-sequence approach interleaving 2D imaging of the aortic root and 3D imaging of the whole left ventricle using highly accelerated k-t PCA was implemented. Rest perfusion imaging was performed in ten healthy volunteers after administration of a Gadolinium-based CA at low (0.025 mmol/kg b.w.) and high dose (0.1 mmol/kg b.w.). Arterial input functions extracted from the 2D and 3D images were analysed for both doses. Myocardial contrast-to-noise ratios (CNR) were compared across volunteers and doses. Variations of myocardial perfusion estimates between volunteers and across myocardial territories were studied. RESULTS: High CA dose imaging resulted in strong non-linearity of the arterial input function in the 3D images at peak CA concentration, which was avoided when the input function was derived from the 2D images. Myocardial CNR was significantly increased at high dose compared to low dose, with a 2.6-fold mean CNR gain. Most robust myocardial blood flow estimation was achieved using the arterial input function extracted from the 2D image at high CA dose. In this case, myocardial blood flow estimates varied by 24% between volunteers and by 20% between myocardial territories when analysed on a per-volunteer basis. CONCLUSION: Interleaving 2D imaging for arterial input function assessment enables robust quantitative 3D myocardial perfusion imaging at high CA dose.

Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model.

BACKGROUND: Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. OBJECTIVES: To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. METHODS: Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. RESULTS: CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. CONCLUSION: Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.

Ultrasound based assessment of coronary artery flow and coronary flow reserve using the pressure overload model in mice.

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow reserve (CFR) in humans. Reduced CFR is accompanied by marked intramyocardial and pericoronary fibrosis and is used as an indication of the severity of dysfunction. This study explores, step-by-step, the real-time changes measured in the coronary flow velocity, CFR and systolic to diastolic peak velocity (S/D) ratio in the setting of an aortic banding model in mice. By using a Doppler transthoracic imaging technique that yields reproducible and reliable data, the method assesses changes in flow in the septal coronary artery (SCA), for a period of over two weeks in mice, that previously either underwent aortic banding or thoracotomy. During imaging, hyperemia in all mice was induced by isoflurane, an anesthetic that increased coronary flow velocity when compared with resting flow. All images were acquired by a single imager. Two ratios, (1) CFR, the ratio between hyperemic and baseline flow velocities, and (2) systolic (S) to diastolic (D) flow were determined, using a proprietary software and by two independent observers. Importantly, the observed changes in coronary flow preceded LV dysfunction as evidenced by normal LV mass and fractional shortening (FS). The method was benchmarked against the current gold standard of coronary assessment, histopathology. The latter technique showed clear pathologic changes in the coronary artery in the form of peri-coronary fibrosis that correlated to the flow changes as assessed by echocardiography. The study underscores the value of using a non-invasive technique to monitor coronary circulation in mouse hearts. The method minimizes redundant use of research animals and demonstrates that advanced ultrasound-based indices, such as CFR and S/D ratios, can serve as viable diagnostic tools in a variety of investigational protocols including drug studies and the study of genetically modified strains.

In vitro assessment of physiological impact of recipient artery intervention on the contralateral donor artery.

BACKGROUND: Donor artery fractional flow reserve (FFR) often improves after treatment of recipient artery stenosis, but the physiological mechanism underlying this phenomenon has not been elucidated. This study aimed to assess two novel equations that explain the donor-recipient artery interaction. METHOD: Eq. (A) predicts the donor artery FFR after complete release of recipient artery stenosis, while Eq. (B) predicts the donor artery FFR after partial release of recipient artery stenosis. Eq. (B) is a general form of Eq. (A). FFR'1−pred = ((FFR1−CFI1)(FFR2−CFI2)−CFI1CFI2(1−FFR1)(1−FFR2)+CFI1(1−FFR1)(1−CFI2))/((1−C FI1)(FFR2−CFI2)) (A) FFR''1−pred = ((FFR1−CFI1)(FFR2−CFI2)−CFI1CFI2(1−FFR1)(1−FFR2)+CFI1(1−FFR1)(1−CFI2))FFR'2/((1−C FI1)(FFR2−CFI2)) (B) Eqs. (A) and (B) were assessed using an in vitro model of coronary circulation with a collateral channel connecting the donor and recipient arteries. RESULTS: The donor artery FFR always improved after releasing the recipient artery stenosis. A good linear correlation was found between the predicted FFR of Eq. (A) and the actual FFR (n=40, r=0.95, p<0.0001) and between the predicted FFR of Eq. (B) and the actual FFR (n=40, r=0.94, p<0.0001). CONCLUSIONS: Eqs. (A) and (B) accurately predicted the true FFR value of the donor artery in a coronary circulation model and explain the donor-recipient artery interaction observed in clinical practice.