Non-invasive Coronary Flow Reserve Research Articles

Correlation of Non-Invasive Transthoracic Doppler Echocardiography with Invasive Doppler Wire-Derived Coronary Flow Reserve and Their Impact on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention.

Background: Coronary microvascular dysfunction is associated with adverse prognosis after ST-segment elevation myocardial infarction (STEMI). We aimed to compare the invasive, Doppler wire-based coronary flow reserve (CFR) with the non-invasive transthoracic Doppler echocardiography (TTDE)-derived CFR, and their ability to predict infarct size. Methods: We included 36 patients with invasive Doppler wire assessment on days 3-7 after STEMI treated with primary percutaneous coronary intervention (PCI), of which TTDE-derived CFR was measured in 47 vessels (29 patients) within 6 h of the invasive Doppler. Infarct size was assessed by cardiac magnetic resonance at a median of 8 months. Results: The correlation between invasive and non-invasive CFR was modest in the overall cohort (rho 0.400, p = 0.005). It improved when only measurements in the LAD artery were considered (rho 0.554, p = 0.002), with no significant correlation in the RCA artery (rho -0.190, p = 0.435). Both invasive (AUC 0.888) and non-invasive (AUC 0.868) CFR, measured in the recanalized culprit artery, showed a good ability to predict infarct sizes ≥18% of the left ventricular mass, with the optimal cut off values of 1.85 and 1.80, respectively. Conclusions: In patients with STEMI, TTDE- and Doppler wire-derived CFR exhibit significant correlation, when measured in the LAD artery, and both have a similarly strong association with the final infarct size.

Validation of a new model of non-invasive functional assessment of coronary lesions by computer tomography fractional flow reserve

Introduction and objectivesComputed tomography of coronary arteries (CTCA) is emerging as the gold standard in the initial evaluation of chest pain. The aim of this study is to calculate the diagnostic performance and clinical usefulness of numerical models of arterial channels flow to assess non-invasive coronary fractional flow reserve by computed tomography (FFRct) compared to assessment by invasive angiography (FFR). MethodsComputation of FFR from CTCA images was performed on 39 vessels in 32 patients who followed the usual clinical protocol including invasive coronary angiography and FFR following the usual clinical protocol. From the segmentation of the CTCA images, 3D geometry is obtained, and computational fluid dynamics techniques are applied to accurately reproduce the circulation of blood considering steady and unsteady circulatory conditions. Additional parameters as wall shear stress, stenosis resistance index and ΔFFRct were also calculated. ResultsThe results obtained show a good correlation between FFRct and invasive FFR, without obtaining false positives values. In addition, no differences were observed between the simulations considering steady conditions or those considering the transient. Additional parameters as wall shear stress, stenosis resistance, and ΔFFRct also showed a good correlation with the invasive values. ConclusionsThis new model for calculating the FFRct from non-invasive 3D medical images of coronary tree has shown good agreement with those obtained using invasive techniques. Parameters as wall shear stress, stenosis resistance and ΔFFRct provide useful information that could be helpful in medical decision-making in those situations with FFR values close to the cut-off zone.

The non-invasive coronary flow reserve predicts exercise capacity in patients undergoing cardiac rehabilitation

The benefit of exercise on peripheral muscles is established but the exact role of the coronary microcirculation in exercise capacity after cardiac rehabilitation (CR) is unclear. Our aim was to test the relationship between non-invasive coronary flow reserve (CFR) and exercise capacity in patients undergoing CR after acute myocardial infarction (AMI). CFR was performed by transthoracic Doppler echocardiography in the left anterior descending artery 24 h after angioplasty (CFR1) and after 20 sessions of CR program (at 4 ± 1 months)(CFR2) in 60 consecutive patients (57 ± 11 years, 30% women) with an anterior AMI successfully treated by primary coronary angioplasty. CFR was performed in a modified parasternale view using intravenous adenosine infusion (0.14 mg/kg/min within 2 minutes). CR program consisted of a half hour of fractioned exercise added of a half hour session of general gymnastics and bodybuilding. To test the exercise capacity, symptom limited exercise echocardiography was performed just after the CFR2, in a semi-supine position, starting at 25 watts, with 20-25 watts increments of workload every two minutes. CFR was measured successfully in all patients, and CFR2 was significantly higher than CFR1 (2.9 ± 0.65 vs. 1.9 ± 0.4, P < 0.001). Though CFR1 was correlated to left ventricular systolic function and its improvement at follow-up (all, P < 0.01), CFR2 was independently related to exercise capacity (mean workload 100 ± 30 watts, percent maximal heart rate 83 ± 12%, no ischemia, no new wall motion abnormalities in all tests) after adjusting for age, sex, and body mass index ( r = 0.6, P < 0.01). CFR predicts exercise capacity in patients undergoing a CR program after AMI. The improvement of CFR contributes to cardiac performance.

Time-dependent improvement in coronary flow reserve in collateral donor artery following successful recanalization of the Coronary Chronic Total Occlusion

Abstract Background Coronary chronic total occlusion (CTO) is characterized by the presence of collateral blood vessels which can provide additional blood supply to CTO-artery dependent myocardium. Successful CTO recanalization is followed by significant decrease in collateral donor artery blood flow and collateral derecruitment. Purpose Study aim was to assess time-dependent changes in coronary flow reserve (CFR) in collateral donor artery after CTO recanalization and identify factors that influence these changes. Methods Our study enrolled 31 patients with CTO scheduled for percutaneous coronary intervention (PCI). Non-invasive CFR was measured before PCI in collateral donor artery, and 24h and 6 months post-PCI in CTO and collateral donor artery. Gated SPECT MIBI was performed before PCI, while quality of life was assessed by Seattle angina questionnaire (SAQ) pre-PCI, and 6 months after PCI. Results Collateral donor artery showed significant increase in CFR 24h after CTO recanalization compared to pre-PCI values (2.30±0.49 vs. 2.71±0.45, p=0.005), which remained unchanged after 6 months (2.68±0.24). Maximum baseline blood flow velocity of the collateral donor artery showed significant decrease measured 24h post-PCI compared to pre-PCI values (0.28±0.06 vs. 0.24±0.04m/s), and remained similar after 6-months. There was no significant difference in maximum hyperemic blood flow velocity pre-PCI, 24h and 6 months post-PCI. CFR change of the collateral donor artery 24h post-PCI compared to pre-PCI values showed inverse correlation with left ventricle ejection fraction (LVEF) measured on SPECT. CFR changes showed no correlation with the changes in quality of life assessed by SAQ post-PCI compared to pre-PCI. Conclusions Significant increase in CFR of the collateral donor artery was observed within 24h after successful recanalization of CTO artery, which maintained constant after the 6 months follow-up. This increase was largely driven by the significant reduction in the maximum baseline blood flow velocity within 24h after CTO recanalization compared to pre-PCI values. Our results suggest that possible benefit of CTO recanalization could be the improvement in physiology of the collateral donor artery. Funding Acknowledgement Type of funding source: None

P6220The non-invasive coronary flow reserve predicts exercise capacity in patients undergoing cardiac rehabilitation

Abstract Background The benefit of exercise on peripheral muscles is established but the exact role of the coronary microcirculation in exercise capacity after cardiac rehabilitation (CR) is unclear. Objective: Our aim was to test the relationship between non-invasive coronary flow reserve (CFR) and exercise capacity in patients undergoing CR after acute myocardial infarction (AMI). Methods CFR was performed by transthoracic Doppler echocardiography in the left anterior descending artery 24 h after angioplasty (CFR1) and after 20 sessions of CR program (at 4±1 months) (CFR2) in 60 consecutive patients (57±11 years, 30% women) with an anterior AMI successfully treated by primary coronary angioplasty. CFR was performed in a modified parasternal view using intravenous adenosine infusion (0.14 mg/kg/min within 2 minutes). CR program consisted of a half hour of fractioned exercise added of a half hour session of general gymnastics and body building. To test the exercise capacity, symptom limited exercise echocardiography was performed just after the CFR2, in a semi-supine position, starting at 25 watts, with 20–25 watts increments of workload every two minutes. Results CFR was measured successfully in all patients, and CFR2 was significantly higher than CFR1 (2.9±0.65 vs 1.9±0.4, p&lt;0.001). Though CFR1 was correlated to left ventricular systolic function and its improvement at follow-up (all, p&lt;0.01), CFR2 was independently related to exercise capacity (mean workload 100±30 watts, percent maximal heart rate 83±12%, no ischemia, no new wall motion abnormalities in all tests) after adjusting for age, sex, and body mass index (r=0.6, p&lt;0.01). Conclusion CFR predicts exercise capacity in patients undergoing a CR program after AMI. The improvement of CFR contributes to cardiac performance.

Coronary flow reserve is related to the extension and transmurality of myocardial necrosis and predicts functional recovery after acute myocardial infarction

Few studies have examined the effect of transmurality of myocardial necrosis on coronary microcirculation. The aim of this study was to examine the influence of cardiac magnetic resonance-derived (GE-MRI) structural determinants of coronary flow reserve (CFR) after anterior myocardial infarction (STEMI), and their predictive value on regional functional recovery. Noninvasive CFR and GE-MRI were studied in 37 anterior STEMI patients after primary coronary angioplasty. The wall motion score index in the left descending anterior coronary artery territory (A-WMSI) was calculated at admission and follow-up (FU). Recovery of regional left ventricular (LV) function was defined as the difference in A-WMSI at admission and FU. The necrosis score index (NSI) and transmurality score index (TSI) by GE-MRI were calculated in the risk area. Baseline (BMR) and hyperemic (HMR) microvascular resistance, arteriolar resistance index (ARI), and coronary resistance reserve (CRR) were calculated at the Doppler echocardiography. Bivariate analysis indicated that the CPK and troponin I peak, heart rate, NSI, TSI, BMR, the ARI, and CRR were related to CFR. Multivariable analysis revealed that TSI was the only independent determinant of CFR. The CFR value of >2.27, identified as optimal by ROC analysis, was 77% specific and 73% sensitive with accuracy of 76% in identifying patients with functional recovery. Preservation of microvascular function after AMI is related to the extent of transmurality of myocardial necrosis, is an important factor influencing regional LV recovery, and can be monitored by noninvasive CFR.

4781Obesity and endothelial dysfunction: insights from non-invasive coronary flow reserve

4781Obesity and endothelial dysfunction: insights from non-invasive coronary flow reserve

Noninvasive Coronary Flow Reserve Predicts Response to Exercise in Asymptomatic Severe Aortic Stenosis

In patients with asymptomatic aortic stenosis (AS), exercise stress echocardiography (ESE) provides additional prognostic information beyond baseline. The coronary flow velocity reserve (CFVR) is impaired in AS, but its link with exertion is unknown in this setting. The aim of this study was to test the hypothesis that CFVR could predict exercise capacity and abnormal exercise test results in AS. Noninvasive CFVR and symptom-limited semisupine ESE were prospectively performed the same day in 43 patients with asymptomatic isolated severe AS (mean age, 68.5±11years; 26% women; mean aortic valve area, 0.8±0.16cm2; mean left ventricular ejection fraction, 70±7%). CFVR was performed in the distal part of the left anterior descending coronary artery using intravenous adenosine infusion (140μg/kg/min over 2min), and ESE was performed at an initial workload of 25W with a 20- to 25-W increase at 2-min intervals. An abnormal result on ESE was defined as onset of symptoms at <75% of maximum predicted workload, electrocardiographic ST-segment depression ≥2mm during exercise, increase of systolic blood pressure<20mmHg or decrease in blood pressure, and complex ventricular arrhythmia. Seventeen patients with isolated severe asymptomatic AS, unable to exercise because of extracardiac conditions, served as a comparative group. Resting, hyperemic left anterior descending coronary artery flow velocity and CFVR (2.45±0.8 vs 2.4±0.8) were similar between the group unable to perform ESE and the ESE group (P=NS for all). Compared with patients with normal results on ESE, those with abnormal results on ESE (n=22) were older, had higher E/e' ratios, had higher resting left anterior descending coronary artery flow velocities (39±12 vs 31±8cm/sec), and had lower CFVR (2.01±0.3 vs 2.85±0.7; P<.01 for all). Furthermore, CFVR was significantly correlated with age, changes in transvalvular pressure gradient and left ventricular ejection fraction with exercise, workload (in watts), and exercise duration (P<.05 for all). After adjusting for other variables, CFVR remained independently correlated with exercise duration, workload, and abnormal results on ESE (P<.01 for all). On receiver operating characteristic curve analysis, CFVR<2.3 was the best cutoff to predict abnormal results on ESE (area under the curve=0.88±0.06, P<.01). In patients with asymptomatic severe AS, noninvasive CFVR is correlated with exercise duration and workload, and low CFVR predicts abnormal results on ESE with good accuracy.

Coronary flow reserve in mitral stenosis before and after percutaneous balloon mitral valvuloplasty.

We aimed to evaluate the coronary flow reserve (CFR) before and after percutaneous balloon mitral valvuloplasty (PBMV) in patients with mitral stenosis (MS) and its association to clinical events. A prospective study included 45 patients with mitral stenosis candidate for PBMV (age 38 ± 19 years, 27 were females) and 20 with matched age and sex, healthy controls were included in the study. Noninvasive CFR was measured using transthoracic echocardiography and utilizing adenosine stress echocardiography (0.14mg/kg/min) before PMBV, and one weak post PBMV using multi-tract balloon valvuloplasty technique. CFR was significantly lower in patients with MS compared to controls (P < 0.001). Moreover the CFR was significantly increased post-PBMV (P < 0.001) associated with significant increase in LVEF% (P < 0.05), decrease in systolic pulmonary artery pressure (P < 0.001), significant increase in TAPSE (P < 0.001). CFR was significantly correlated with the degree of change (Δ) in MVA, TAPSE, LVEF%, mean mitral PG and sPAP (r = 0.77, P < 0.001, r = 0.63; P < 0.001; r = 0.42; P < 0.05; r = -0.81; P < 0.001 and r = -0.65; P < 0.001). Mitral valve stenosis was associated with significantly impaired coronary flow reserve that significantly improved after PMBV. The improved CFR values were significantly correlated with the gain in the MVA and the improvement in the functions of both left and right ventricles.

Clinical significance of noninvasive coronary flow reserve assessment in patients with ischemic heart disease.

The importance of physiologic assessments in ischemic heart disease is well recognized. Coronary flow reserve (CFR) is a novel physiologic imaging biomarker that complements both anatomic and semiquantitative perfusion assessments of coronary artery disease (CAD) severity. Beyond this, assessment of CFR may provide clinical insights useful for refining diagnosis, prognosis, and eventually, management of patients along the full range of ischemic heart disease phenotypes, from multivessel obstructive CAD to diffuse coronary microvascular dysfunction. We begin by defining the concept of noninvasive CFR, specifically focusing on quantification of blood flow using PET, for which robust observational data exist. Next, we describe the continuum of cardiovascular risk by CFR values in patients across the anatomic spectrum of CAD, including those with diabetes, chronic kidney disease, and nonobstructive CAD and coronary microvascular dysfunction. Finally, we summarize the impact of CFR on prognosis, with a focus on future directions for management strategies and potential novel therapies, particularly in patients with very low CFR and less obstructive CAD. This latter phenotype may provide a critical link to understanding hidden biological risk of ischemic heart disease in vulnerable populations, including women and patients with heart failure with preserved ejection fraction, metabolic syndrome, cardio-oncologic complications, and inflammatory-related disease.

Assessment of left anterior descending artery stenosis of intermediate severity by fractional flow reserve, instantaneous wave-free ratio and non-invasive coronary flow reserve

Ninety-four stable consecutive patients (mean age, 68±10years; 19 women) with angiographic proximal or mid LAD stenosis of intermediate severity (40-70% diameter stenosis on quantitative coronary angiography), were prospectively studied. They underwent IFR that was calculated as a trans-lesion pressure ratio during a specific period of baseline diastole, FFR with intracoronary bolus adenosine (180μg), and CFR using intravenous adenosine (140μg/kg/min over 2min) in the distal part of the LAD, the same day. CFR was defined as hyperemic peak diastolic LAD flow velocity divided by baseline flow velocity and FFR as distal pressure divided by mean aortic pressure during maximal hyperemia. The mean values of IFR, FFR, and CFR were 0.88±0.07, 0.81±0.09, and 2.4±0.6 respectively. A significant correlation was found between CFR and FFR (R=0.63, curvilinear relationship), FFR and IFR (R=0.6, linear relationship), and between CFR and IFR (R=0.5) (all, P<0.01). Using a ROC curve analysis, the best cut-off to detect a significant lesion based on FFR assessment (FFR≤0.8, N=31) was IFR≤0.88 with a sensitivity (Se) of 74%, specificity (Sp) of 73%, AUC 0.81±0.04; and CFR≤2 with a Se=77%, Sp=89%, AUC 0.88±0.04, (all, P<0.001). Based on these cut-offs, discordant results between CFR and FFR were observed in 14 cases (agreement 85%), between CFR and IFR in 26 cases (agreement 72%), and between IFR and FFR in 26 cases (agreement 72%). In stable patients with LAD stenosis of intermediate severity, non-invasive CFR is a useful tool to detect a significant lesion based on FFR. Furthermore, there was a better correlation and agreement between CFR and FFR than with IFR.

Correlation between coronary artery calcium score and noninvasive coronary flow reserve

Correlation between coronary artery calcium score and noninvasive coronary flow reserve

Noninvasive Detection of Cardiac Allograft Vasculopathy by Stress Exercise Echocardiographic Assessment of Myocardial Deformation

The aim of this study was to evaluate the value of noninvasive assessment of cardiac allograft vasculopathy (CAV) in heart-transplanted patients by exercise stress myocardial deformation and coronary flow reserve (CFR) assessment. Fifty-eight heart-transplanted patients underwent semisupine exercise echocardiography with assessment of left ventricular (LV) longitudinal myocardial deformation. CAV was assessed by coronary angiography and noninvasive CFR by (15)O-H2O positron emission tomographic imaging and Doppler echocardiography. Patients were divided into three groups on the basis of angiographic CAV: no CAV (n=21), mild CAV (n=19), and severe CAV (n=18). Patients with severe CAV had significantly lower LV global longitudinal strain (GLS) at rest (no CAV, -16±2%; mild CAV, -15±2%; severe CAV, -12±4%; P<.001), failed to increase LV GLS during exercise (no CAV, -5.7±2.0%; mild CAV, -3.3±2.9%; severe CAV, -0.2±2.8%; P<.0001), and had significantly lower echocardiographic coronary flow velocity reserve (CFVR) (no CAV, 3.2±0.4; mild CAV, 2.7±0.7; severe CAV, 1.8±0.5; P<.0001) and PET CFR (no CAV, 3.4±0.9; mild CAV, 3.1±0.9; severe CAV, 1.9±0.8; P<.0001). Furthermore, patients with mild CAV had significantly lower exercise LV GLS and echocardiographic CFVR than patients with no CAV. Exercise LV GLS, echocardiographic CFVR, and PET CFR were significantly correlated with the presence of severe CAV in a logistic regression model (LV GLS odds ratio, 0.71; 95% CI, 0.60-0.84; P<.0001; echocardiographic CFVR odds ratio: 0.06; 95% CI, 0.01-0.23; PET CFR odds ratio, 0.17; 95% CI, 0.07-0.46). This relation remained significant after adjustment for symptoms and time since transplantation. Noninvasive assessment of LV longitudinal myocardial deformation during exercise is feasible and strongly associated with the presence and degree of CAV. Exercise stress myocardial deformation analysis, echocardiographic CFVR, or PET CFR may serve as a noninvasive model for the detection of CAV.

0090: Comparison between non-invasive coronary flow reserve, instantaneous wave-free ratio, and fractional flow reserve, to assess the functional significance of LAD stenosis of intermediate severity

Assessment of the functional significance of left anterior descending coronary artery (LAD) stenosis of intermediate severity (IS) is challenging. A direct comparison of fractional flow reserve (FFR), instantaneous wave-free ratio (IFR), and non-invasive coronary flow reserve (CFR) has never been performed. Our objective was to test the usefulness of noninvasive CFR by comparison to invasive FFR and IFR in patients with LAD stenosis of angiographic IS and stable coronary artery disease. 58 stable consecutive patients (mean age, 68±10 years; with angiographic proximal or mid LAD stenosis of IS (40-70% diameter stenosis on quantitative coronary angiography), no previous anterior myocardial infarction, were prospectively studied. They underwent iFR which was calculated as a trans-lesion pressure ratio during a specific period of baseline diastole, FFR with intracoronary bolus adenosine (150μg), and CFR using intravenous adenosine (140μg/kg/min over 2min) in the distal part of the LAD, the same day. CFR was defined as hyperemic peak diastolic LAD flow velocity divided by baseline flow velocity, and FFR was defined as distal pressure divided by mean aortic pressure during maximal hyperemia. The mean values of iFR, FFR, and CFR were 0.88±0.07, 0.81±0.08, and 2.4±0.6 respectively. A significant correlation was found between CFR and FFR (r=0.72, curvilinear relationship), FFR and IFR (r=0.63, linear relationship), and between CFR and IFR (r=0.44) (all, p<0.01). Using a ROC curve analysis, the best cut-off to detect a significant lesion based on FFR assessment (FFR <0.8, n=16) was iFR ≤0.86 with a sensitivity (Se) of 75%, specificity (Sp) of 81%, AUC 0.8±0.05; and CFR ≤2 with a Se of 82%, Sp of 85%, AUC 0.9±0.03, (all, p<0.001). Based on these cut-offs, discordant results between CFR and FFR were observed in 9 cases (accuracy 84%), between CFR and iFR in 14 cases (accuracy 76%), and between iFR and FFR in 11 cases (accuracy 81%). In stable patients with LAD stenosis of IS, non-invasive CFR is a useful tool to detect a significant lesion based on FFR. Furthermore, CFR is better correlated to FFR than to iFR, and its accuracy seems as good as iFR in this setting.

Abstract 14579: Peak Myocardial Blood Flow versus Noninvasive Coronary Flow Reserve for Prediction of Future Events

Background: Impaired coronary flow reserve (CFR) is an early manifestation of coronary artery disease (CAD), even in vessels free of angiographic stenosis. The aim of this analysis is to determine the differential role peak myocardial blood flow (MBF) or noninvasive CFR in predicting future events. Methods: We included 3,003 consecutive patients with known or suspected CAD (mean age 61±11years, 42% females) who underwent rubidium-82 rest/stress positron emission tomography (PET) for clinical indications. Rest and peak MBF were calculated with factor analysis and a 2-compartment kinetic model and were used to calculate CFR. Patients were followed up for a median duration of 1.4 years (interquartile range, 0.5-1.8 years) for the incidence of cardiac death or myocardial infarction. (CDMI). Multiple Cox regression models were used to determine the prognostic value of peak MBF and CFR and the incremental value of peak MBF over CFR. Results: The included cohort has prevalence of CAD risk factors: Diabetes (60%), hypertension (87%) and dyslipidemia (85%). A total of 40% patients had evidence of perfusion defects (Sum stress score&gt;3). After a median follow up duration of 1.4 years, 140 patients (4.7%) experienced CD/MI. In multivariate Cox regression adjusted for Duke clinical risk score, resting ejection fraction and SSS, both CFR (Hazard Ratio 0.70, 95% CI 0.54 -0.89, p=0.005) and peak MBF (Hazard Ratio 0.71, 95% CI 0.57 -0.89, p=0.003) were independent predictors of CDMI. (Adding peak MBF added incremental prognostic value over CFR. (Area under the curve increased from 0.776 to 0.793, p=0.021). Conclusion: Noninvasively measured MBF and CFR are independent predictors of CDMI in patients with known or suspected CAD. Peak MBF adds incremental prognostic value over noninvasive CFR.

Systolic anterior motion of the mitral valve in tako-tsubo cardiomyopathy: Still a matter of debate?

We present a case which developed a typical tako-tsubo-like cardiomyopathy (TTC) during dobutamine stress echocardiography (DSE). Its originality is related to several findings, which have never been described simultaneously in the same patient. This 63-year-old woman with normal coronary angiography and no evidence of coronary vasospasm had a biphasic response to DSE, a finding which usually occurs in coronary artery disease. Moreover, the symmetric extensive wall motion abnormalities (WMA) occurred simultaneously with the development of a systolic anterior motion of the mitral valve (SAM) and left ventricular obstruction, and was clinically asymptomatic. Although in TTC the stunning usually occurs for several days, WMA and SAM resolved within few minutes after cessation of dobutamine and administration of a beta-blocker. And finally, exercise echo performed at the same target heart rate few days later did not induce neither a SAM nor WMA, which suggests that left ventricular obstruction could have played a role in the pathogenesis of this case by supply-demand mismatch. Concomitant coronary microvascular dysfunction was also demonstrated by a reduction of the non-invasive coronary flow reserve in the distal part of the left anterior descending artery.

2D.07

Objective: Coronary flow reserve (CFR) is a predictor of coronary artery disease. Inhalation of high concentration of the anaesthetic isoflurane (ISO) represents a non-invasive method to induce coronary vasodilation in mice avoiding intravenous adenosine infusion. However, not consistent protocols, especially concerning the time courses of the anesthesia administration, are reported. Aim of this work was to study the correct time course of coronary artery vasodilation. Design and method: Non-invasive 40 MHz Doppler ultrasound (VEVO2100, VisualSonics) was used to measure left coronary flow velocity at baseline (B, ISO1%) and at hyperemia (H, ISO2.5%). For six adult male mice (strain C57BL6, 6 months), isoflurane concentration was maintained at 1% for a 6-min period and then increased to 2.5% for the further 30 minutes. PW-Doppler images were acquired every two minutes and Velocity Time Integral (VTI) values were calculated for each time point providing VTI-time curves. Two mathematical models (sigmoid and exponential) were used to fit the data and the model providing the best fitting was used to calculate the mean time needed to reach the 90% of the plateau value (TT90). The obtained TT90 value was used to identify the duration of the high-isoflurane inhalation phase and the experiment was then repeated in ten mice (same strain and age) using the new time duration. CFR measurements (calculated as VTI(H)/VTI(B)) obtained in these conditions (CFRnew) were compared with those measured using a hyperemia duration as found in literature (approximately 4 minutes) (CFR4 min). Results: The fitting with the sigmoid model provided a lower total Absolute-Sum-of-Squares value than the exponential model (211.6 mm2 vs 405.1 mm2). The sigmoid model provided a TT90 measurements equal to 17.4 ± 6.9 minutes. Accordingly, the time point for the maximal flow was then fixed to 20.5 minutes (14 minutes of ISO2.5% after 6 minutes of ISO1%). CFR4 min values (2.10 ± 0.57) amounted to the 78.1% of CFRnew (2.8 ± 0.87) and the Bland-Altman analysis provided a significant bias of 0.69. Conclusions: These data suggest that short hyperemia durations cause a CFR underestimation; moreover, these results might be useful for the optimization of a standardized protocol for the non-invasive CFR evaluation in mice.

Abstract 15094: Prevalence of Coronary Microvascular Dysfunction in Women With Angina and No Obstructive Coronary Artery Disease: Preliminary Results From the iPower Study

Background: Women are more often than men found to have no obstructive coronary artery disease (CAD) when evaluated with a coronary angiogram (CAG) due to angina pectoris and suspected ischemic heart disease. Coronary microvessel dysfunction (CMD) is a possible explanation, and can be assessed by transthoracic Doppler echocardiography (TTDE) with measurement of coronary flow reserve (CFR). Reduced CFR carries an adverse prognosis despite absence of obstructive CAD. The aim of the ongoing iPower study is to evaluate CFR in women with angina pectoris and no obstructive CAD. Methods: Women with angina pectoris and a CAG without obstructive coronary artery disease (&gt;50%) are systematically invited to participate. Assessment includes demographic and clinical data, blood samples and TTE during rest and high-dose dipyridamole stress (0.84mg/kg) with measurement of CFR by Doppler of the left anterior descending artery. Results: To date (May 21st 2014) 3500 women have been screened (flowchart), 793 women have been included (response rate 23%). Mean age was 62.4 (+/-9.6) and the burden of risk factors was relatively high (Table 1). CFR was successfully measured in 763 patients (96%). Median (IQR) CFR was 2.4 (2.0-2.8). Cut-off point for CMD of both 2 and 2.5 has been used previously. In this population, 214 (28%) had a CFR≤2 and 468 (61%) a CFR≤2.5. Conclusions: To our knowledge, iPower is the largest and most comprehensive study systematically assessing CMD in women with angina pectoris and no obstructive CAD. Non-invasive CFR assessment is feasible, and microvascular function impaired in a large proportion. Future follow-up will determine the prognostic value of CFR as a measure of CMD.

Evaluation of myocardial ischemia caused by left anterior descending coronary artery disease using coronary flow reserve

Objective To explore the value of coronary flow reserve(CFR) evaluating myocardial ischemia measured by adenosine triphosphate (ATP) stress transthoracic Doppler echocardiography (TTDE),and the feasibility of CFR to predict coronary stenosis.Methods Fifty-four patients suffering chest pain with known or suspected coronary artery disease were performed ATP stress TTDE to measure resting and maximum expansion coronary blood flow velocity and calculate CFR.all patients were performed by coronary angiography (CAG) and single-photon emission computed tomography (SPECT) myocardial perfusion imaging.Results ① To evaluate myocardial ischemia,there was not statistical significant difference between non-invasive CFR and SPECT myocardial perfusion imaging(P ＞0.05).CFR≤2.0 was the best cutoff value for evaluating myocardial ischemia which yielded a sensitivity of 93.3 ％ and specificity of 89.7％.②Coronary artery stenosis was negatively correlated with CFR (P ＜0.001).ROC curve analysis demonstrated that CFR≤ 1.60 yielded a sensitivity of 92.3％ and specificity of 73.3％ to predict coronary stenosis significantly.Conclusions CFR measured by ATP stress TTDE can evaluate myocardial ischemia of coronary artery disease and predict LAD significant stenosis before CAG.Using CFR and CAG has important clinical value for choosing treatment of stable coronary artery disease. Key words: Echocardiography, stress; Fractional flow reserve, myocardial; Myocardial ischemia; Coronary stenosis; Adenosine triphosphate

Effects of ranolazine on noninvasive coronary flow reserve in patients with myocardial ischemia but without obstructive coronary artery disease.

Ranolazine reduces the Na-dependent calcium overload via inhibition of the late sodium current, improving diastolic tone and oxygen handling during myocardial ischemia. In patients with angina, evidence of myocardial ischemia, but no obstructive coronary artery disease (CAD), abnormal coronary autoregulation plays a key role. Transthoracic Doppler-derived coronary flow reserve (CFR) is an index of coronary arterial reactivity and decreases in both microvascular dysfunction and coronary artery stenosis. The aim of this study was to assess the effect of ranolazine on CFR in this group of patient. Fifty-eight (39M, 19F) patients with angina and evidence of myocardial ischemia, but no obstructive CAD, were enrolled in a double-blind, placebo-controlled trial. Participants were assigned to ranolazine (29) or placebo (29) for 8 weeks (up to 500 mg twice a day). CFR was determined as the ratio of hyperemic, induced by intravenous dypiridamole administration, to baseline diastolic coronary flow velocity. CFR was assessed before and after 8-week therapy. CFR was successfully performed in all patients. There were no significant differences in baseline characteristics and CFR between ranolazine and placebo group. After 8 weeks CFR significantly increased in ranolazine group (2.54 ± 0.44 vs. 1.91 ± 0.31; P = 0.005) but not in placebo group (1.99 ± 0.32 vs. 1.94 ± 0.29; P = ns). No patient dropped out during 8 weeks therapy. Side effects were similar in both groups. Ranolazine is able to improve CFR in these patients. This is probably due to improvement in abnormal coronary autoregulation, both reducing baseline diastolic coronary flow velocity and increasing hyperemic diastolic coronary flow velocity.