Relative Coronary Flow Reserve Research Articles

Rest/stress myocardial perfusion imaging by positron emission tomography with 18F-Flurpiridaz: A feasibility study in mice

BackgroundMyocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice. MethodsRest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7–8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. ResultsTracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm−3·min−1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm−3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman’s coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice. ConclusionOur findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

Značaj relativne koronarne reserve protoka kod pacijenata sa mikrovaskulrnom disfunkcijom u proceni značajne koronarne stenoze

Introduction: Coronary flow reserve (CFR) is defined as a ratio of hyperemic-to-basal coronary flow velocity and it can be measured by a variety of methods. Transthoracic Doppler echocardiography (TTE) CFR became useful method to assess functional significance of coronary artery stenosis in both left anterior descending (LAD) and posterior descending coronary artery (PD). CFR is combined measure of the capacity of epicardial coronary artery and microcirculation to achieve maximal blood flow in response to hyperemic stimulation. Thus in patients with already impaired microcirculation and accordingly CFR, differentiation from presence of significant coronary stenosis is difficult without known coronary angiography. Case report: We present a case of patient with hypertrophic cardiomyopathy and diabetes, where relative CFR as the ratio of the CFRs of two coronary arteries helped us in decision making to do coronarography because of atypical chest pain and fatigue. Conclusion: In patients with known microvascular dysfunction and already impaired CFR, relative CFR might be helpful to differentiate presence of significant epicardial stenosis. Future studies are needed to obtain appropriate clinical implications of relative CFR in everyday practice.

Patient selection for elective revascularization to reduce myocardial infarction and mortality: new lessons from randomized trials, coronary physiology, and statistics.

As stated in American College of Cardiology/American Heart Association Guidelines, randomized trials have not demonstrated that elective percutaneous coronary intervention (PCI) reduces myocardial infarction (MI) or mortality over medical treatment. Even the Fractional Flow Reserve Guided PCI Versus Medical Therapy in Stable Coronary Disease (FAME 2) trial showed no statistically significant benefit of PCI over the deferred group by traditional intention-to-treat, nonbenchmark analysis starting at randomization that includes procedure-related events. Benchmark analysis in FAME 2 beginning 1 week after PCI removed procedure-related events that counterbalanced subsequent reduced MI and mortality compared with the deferred group. Meta-analysis of the literature on risk of events related to fractional flow reserve (FFR), including FFR Versus Angiography in Multivessel Evaluation (FAME), and other physiological measures of severity reveal an underappreciated, powerful interdependence among physiological severity of stenosis, diffuse coronary artery disease (CAD), event rates, sample size, and statistical certainty of differences. This analytic review synthesizes an evidenced-based, quantitative hypothesis and potential solution to this issue based on hard data from the literature by coauthors of diverse cardiovascular disciplines in trial design, biostatistics, invasive procedures, coronary physiology, fluid dynamics, coronary pathology, and quantitative imaging. Our synthesis elucidates a dual hypothesis for failure of elective PCI in stable CAD to reduce MI or mortality and novel trial design for selecting patients for whom PCI will likely reduce these events. First, a large burden of global diffuse CAD carries a high risk of coronary events unmitigated by PCI of a focal stenosis. Second, focal stenosis severity in previous randomized revascularization trials has been too modest without objectively quantified sufficient severity to observe benefit of PCI. In previous trials, mixture of diffuse coronary disease and intermediate stenosis may not incur high enough risk for potential benefit by PCI for sample size of reported trials. Greater quantitative severity with …

Effect of simvastatin on coronary flow reserve in patients with atherosclerosis and hypercholesterolemia: an intracoronary Doppler study

Early stages of coronary atherosclerosis are accompanied by a functional impairment of coronary vasodilator capacity and endothelial dysfunction. Reduced coronary flow reserve has been reported in patients with hypercholesterolemia, despite angiographically normal coronary arteries. The aim of the study was to evaluate the effect of simvastatin on coronary flow reserve. The study was an open non-placebo-controlled serial investigation in which every patient acted as his own control: 36 male patients with hypercholesterolemia and a non-significant coronary artery lesion in a not previously revascularized coronary artery. Intracoronary Doppler measurements were performed. Coronary flow reserve, relative coronary flow reserve and average peak velocity were performed at baseline, after 3 months on a lipid-lowering diet (control period), and after another 12 months of simvastatin 40 mg/day. In the same patient cohort, significant reduction in lesion plaque plus media has been demonstrated by intravascular ultrasound. Changes in coronary flow reserve were not influenced by either diet or simvastatin (2.5+/-0.6 vs. 2.6+/-0.5 vs. 2.6+/-0.6, P=ns). Maximum hyperemic flow (34.8+/-12.2 vs. 36.7+/-12.5 vs. 42.5+/-13.1, P<0.001) as well as resting flow (14.3+/-5.3 vs. 14.5+/-4.4 vs. 16.6+/-4.6, P<0.001) increased significantly after 12 months simvastatin therapy. Despite plaque plus media, regression simvastatin therapy for 12 months does not affect coronary flow reserve obtained using serial intracoronary Doppler studies. Simvastatin, however, increases the hyperemic flow velocity.

Convalescent stage coronary flow reserve and late myocardial morphologic outcomes in patients with first anterior acute myocardial infarction.

Microvascular damage immediately after reperfusion therapy is an independent predictor of left ventricular function in patients with acute myocardial infarction (AMI). However, its recovery may vary among individuals and the relationship between convalescent stage microvasculature and late myocardial morphologic change is unclear. Patients treated with coronary angioplasty within 12 h of their first anterior AMI were enrolled in this study. Coronary flow reserve (CFR) was measured 3 weeks post AMI, in both branches of the left coronary artery: culprit (left anterior descending artery: LAD) and non-culprit (left circumflex artery: LCX). Left ventriculography was performed at 3 weeks and 6 months post AMI and compared. Seventeen patients showed abnormal CFR in the LAD (Group 1: CFR<2), whereas 20 patients showed normal CFR (Group 2: CFR >/=2). Percent changes of end-diastolic volume tended to be higher in Group 1 than in Group 2 (11.8+/-21.6% vs -1.3+/-14.4%, p=0.056), and %changes of end-systolic volume was significantly smaller in Group 2 (11.8+/-22.1% vs -8.7+/-25.1%, p<0.05). A statistically significant correlation was found between absolute and relative CFR in the LAD and %change of end-systolic volume (r=-0.58: p<0.001, and r=0.40: p<0.05, respectively). Microvascular function in the convalescent stage may be related to these favorable changes.

P2224 Validation of fractional and relative coronary flow reserve measurements in patients with prior myocardial infarction

P2224 Validation of fractional and relative coronary flow reserve measurements in patients with prior myocardial infarction

Current concepts in coronary physiology for the interventionalist.

Coronary angiography remains the 'gold standard' for the diagnosis of epicardial coronary disease. However, precise quantification of stenosis severity is limited because of the complex three-dimensional geometry of epicardial plaques. To assist the angiographer in lesion assessment, several physiologic measurements have been developed to evaluate stenosis severity, including coronary flow reserve, relative coronary flow reserve and fractional flow reserve. Physiologic lesion assessment can also be an invaluable tool in coronary intervention, evaluating efficacy of angioplasty and stent deployment.

Coronary hemodynamics of stent implantation after suboptimal and optimal balloon angioplasty

ObjectivesThis study was performed to evaluate hemodynamic alterations of stent implantation after Doppler flow–guided balloon angioplasty (BA). BackgroundThere is controversy regarding the effect of stent implantation on coronary hemodynamics after suboptimal and optimal BA. MethodsA total of 523 of 620 patients underwent Doppler-guided BA in the setting of a multicenter study and were analyzed before and after additional stent implantation. Balloon angioplasty was considered optimal when the diameter stenosis (DS) was ≤35% and coronary flow reserve (CFR) was >2.5 and suboptimal if these two criteria were not met. Coronary flow reserve was also measured in an angiographically normal artery to determine relative CFR. Patients were followed for 12 months to document major adverse cardiac events (MACE). ResultsThe main difference between patients with suboptimal BA (n = 195 [51%]) and optimal BA (n = 184 [49%]) was a more pronounced increase in baseline blood flow velocity (15 ± 8 to 22 ± 11 vs. 14 ± 8 to 16 ± 10 cm/s, p < 0.01). Coronary flow reserve improved after stent implantation in both patient groups, owing to a reduction in residual lumen obstruction, as determined by angiographic (%DS) and Doppler flow criteria (hyperemic blood flow velocity, relative CFR), and was associated with a decrease in MACE (16% vs. 7% in optimal BA group, p = 0.08; and 27% vs. 11% in suboptimal BA group, p = 0.007). ConclusionsStent implantation enhances CFR after suboptimal and optimal Doppler-guided BA, owing to a reduction in residual lumen obstruction—determined by angiographical and Doppler flow criteria—as the underlying mechanism for an improved clinical outcome.

Usefulness and limitation of relative coronary flow reserve as a prediction of the long term outcome on PTCA for small vessels

Usefulness and limitation of relative coronary flow reserve as a prediction of the long term outcome on PTCA for small vessels

Comparison of Coronary Flow Reserve According to The Degree of Hypokinesia in Dilated Cardiomyopathy With Regional Asynergy

Background and Objectives:Dilated cardiomyopathy (DCMP) is a primary myocardial disease of unknown cause characterized by left ventricular or biventricular dilatation and impaired myocardial been reported in DCMP with generalized hypok contractility. In 1973, Kreulen et al. classified DCMP into two groups-one with generalized hypokinesia and the other with regional asynergy in addition to generalized hypokinesia. Diminished coronary flow reserve has inesia but its mechanism remains obscure. The aim of this study was to investigate the relationship between the degree of microvascular dysfunction and the difference of regional wall motion abnormality in DCMP with regional asynergy. Methods:The subjects of this study were 11 patients (M:F=6:5, mean age:60±15 yrs) a diagnosis of DCMP with regional asynergy, normal sinus rhythm without left bundle branch block and normal coronary angiogram who underwent Doppler wire from September 1997 to December 1999. Left ventricle was divided into three territories according to the coronary arterial distribution by echocardiography (A:coronary artery territory showing regional asynergy, I:coronary artery territory showing intermediate wall motion, P:coronary artery territory showing relatively preserved wall motion). Coronary flow reserve (CFR) was measured at the mid portion of left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA) with 0.014 inch Doppler guide wire before and during intracoronary injection of 12-18 μg of adenosine. Relative coronary flow reserve (rCFR) was obtained by the ratio of the CFR in coronary artery of the territory showing regional asynergy and relatively preserved wall motion to the CFR in coronary artery of the territory showing intermediate wall motion (CFRA/CFRI, CFRP/CFRI). Results:Regional asynergy was observed in LAD The mean CFR was 2.5±0.6 in LAD, territory in 4 (36%) patients, LCX territory in 4 (36%) patients, RCA territory in 3 (28%) patients (p=ns).2.4±0.5 in LCX, 2.4±0.6 in RCA (p=ns). The mean CFR and rCFR in coronary arteries showing regional asynergy were significantly lower than those in coronary arteries showing relatively preserved wall motion (2.1±0.5 vs 2.7±0.6, p<0.05, 0.84±0.12 vs 1.11±0.11, p<0.001). 논문접수일:1999년 5월 29일 심사완료일:1999년 9월 25일 교신저자:서정기, 400-103 인천광역시 중구 신흥동 3가 7-206 인하대학교 의과대학 순환기내과학교실 전화:(032) 890-2445·전송:(032) 890-2447 E-mail:jksmd@inha.com

Update of Coronary Doppler Flow Measurements

As percutaneous coronary revascularization was performed on an increasing number of patients, the indications of many procedures were considered inappropriate because of the lack of objective evidence of significant coronary stenosis. This problem is the result of the limitations of noninvasive tests in assessing the physiological significance of a lesion and poor correlation between anatomy shown by quantitative coronary angiography and physiology of the stenosis. Even with intracoronary ultrasound study, the correlation between morphology and physiological significance has been poor, especially with lesions of intermediate severity. With recent technical improvements, measurement of coronary flow reserve (CFR) by Doppler catheters was advocated as the “gold‐standard” in assessing the physiological significance of epicardial coronary artery stenosis. Advantages and limitations of various Doppler indices commonly used in the catheterization laboratory were discussed. Because of its simple applicability, ease of validation using a clearly cut‐off value, virtual freedom from confounding factors, and usefulness even in the presence of triple vessel disease, fractional flow reserve (FFR) was found to be a better index for physiological assessment than absolute CFR or relative CFR.

Long-term Normalization of the Absolute and Relative Coronary Flow Reserve After Balloon Angioplasty and Stent Implantation

Long-term Normalization of the Absolute and Relative Coronary Flow Reserve After Balloon Angioplasty and Stent Implantation

Long-term normalization of the absolute and relative coronary flow reserve after balloon angioplasty and stent implantation

Long-term normalization of the absolute and relative coronary flow reserve after balloon angioplasty and stent implantation

Additive value of relative coronary flow reserve in the assessment of intermediate coronary artery stenosis: comparison to myocardial stress perfusion imaging

Additive value of relative coronary flow reserve in the assessment of intermediate coronary artery stenosis: comparison to myocardial stress perfusion imaging

Additive Value of Relative Coronary Flow Reserve in the Assessment of Intermediate Coronary Artery Stenosis: Comparison to Myocardial Stress Perfusion Imaging

Additive Value of Relative Coronary Flow Reserve in the Assessment of Intermediate Coronary Artery Stenosis: Comparison to Myocardial Stress Perfusion Imaging

Changes in phasic coronary blood flow velocity profile and relative coronary flow reserve in patients with hypertrophic obstructive cardiomyopathy.

In this study, we both investigated coronary flow velocity in hypertrophic obstructive cardiomyopathy (HOCM) and tested the hypothesis of differing coronary flow reserve (CFR) of coronary arteries perfusing left ventricular regions with nonuniform myocardial hypertrophy by measuring the relative CFR. Coronary flow velocity was assessed in left anterior descending coronary (LAD) and left circumflex (LCX) arteries in 18 patients with HOCM and marked hypertrophy only in the ventricular septum, in 13 patients without obstruction (HCM), and in 9 age- and sex-matched normal subjects at rest, during rapid atrial pacing, and after dobutamine infusion (5 to 30 microg/kg per minute). Relative CFR was estimated as the ratio between absolute CFR of the LAD and absolute CFR of the LCX (LAD/LCX(CF)). At the peak of rapid atrial pacing and during dobutamine stress, LAD/LCX(CF) was reversed in HOCM patients (from 1.25+/-0.11 to 0.82+/-0.07 and 0.79+/-0.06, respectively), whereas it remained unchanged in control subjects (from 1.0+/-0.1 to 1.0+/-0.05 and 1.0+/-0.05, respectively; P<.001). In HCM patients, LAD/LCX(CF) at rest was 1.10+/-0.11, whereas during rapid atrial pacing and dobutamine stress, it was 0.92+/-0.08 and 0.90+/-0.09, respectively. Relative CFR was 0.62+/-0.05 in HOCM patients and 1.05+/-0.05 (P<.001) in normal subjects. There was an inverse correlation between relative CFR and peak systolic outflow tract gradient (r2=.74, P<.001). Regional distribution of hypertrophy in some patients with HOCM resulted in regional impairment of coronary flow. Relative CFR can be used to estimate regional disturbances of coronary flow and may help in patient selection for new interventional therapeutic techniques.

Isolated Defect of Adenosine-Mediated Coronary Vasodilation: Functional Evidence for a New Microangiopathic Entity

Objectives. The present study describes an isolated defect of the coronary vasodilation in response to adenosine in five patients examined for clinically suspected coronary microangiopathy.Background. Coronary microangiopathies can be defined functionally as dysregulation of the microcirculatory vasomotion.Methods. The five patients were compared with 24 control subjects. Coronary flow velocity was measured with an intracoronary Doppler guide wire (0.018 in. [0.046 cm], 12 MHz) at rest and during intracoronary administration of adenosine (80 μg/min and 160 μg/min over 3 min each), papaverine (10-mg bolus) and acetylcholine (30 μg/min over 5 min). Diameters of the epicardial coronary arteries were measured by quantitative coronary angiography.Results. All subjects (patients and control) exhibited angiographically normal epicardial coronary arteries and normal and comparable endothelium-independent and -dependent vasomotion, as assessed with papaverine (mean [± SD] relative coronary flow reserve 2.62 ± 0.66 vs. 2.97 ± 0.88, p = 0.32) and acetylcholine (volumetric coronary flow reserve 2.61 ± 0.27 vs. 2.91 ± 0.67, p = 0.58), respectively. Affected patients were identified by an isolated complete defect of the adenosine-mediated vasodilation compared with control subjects (relative coronary flow reserve in response to 80 μg/min of adenosine 1.08 ± 0.17 vs. 2.45 ± 0.74 [p < 0.001] and 160 μg/min of adenosine 1.03 ± 0.15 vs. 2.89 ± 0.65 [p < 0.001]).Conclusions. These findings are consistent with functional evidence for a new entity of a coronary microangiopathy affecting a subtype of the endothelium-independent vasomotion.(J Am Coll Cardiol 1997;30:103–7)

Future challenges to coronary angioplasty: perspectives on intracoronary imaging and physiology

Several intravascular techniques have been developed with the purpose of achieving optimal guidance for treatment during coronary angioplasty (PTCA). Although the coronary angiographic technique is well established, there are still some inherent limitations. Due to intimal rupture, tears, dissection and thrombus following PTCA treatment, angiography does not allow exact delineation of the true borders of the vessel. Coronary angioscopy is currently the most sensitive method to detect coronary thrombus and can also be used to classify atheromatous plaques. Furthermore, coronary dissection can be detected with more accuracy than with angiography. One limitation associated with angioscopy is the need to occlude the vessel during imaging, which may create myocardial ischaemia. Furthermore, there is presently no method for quantifying angioscopic findings. Intravascular ultrasound produces a cross-sectional image of the vessel, which permits analysis of the layers of the vascular wall. Characterization and classification of various types of plaque can be made because thrombus, lipid, fibrous tissue and calcium have different ultrasonic echogenicity. Flow velocity measurement with the Doppler technique is an interesting approach to the physiological assessment of coronary stenoses. Coronary flow reserve can be estimated with this method and monitoring of the flow signal following angioplasty will aid in the diagnosis of flow-limiting complications. The trans-stenotic pressure gradient is a valuable measure of the haemodynamic importance of a coronary lesion. Trans-stenotic gradients during maximal hyperaemia obtained with a miniaturized pressure transducer yield reliable information regarding the severity of the stenosis, and the pressure values may be used to calculate the relative coronary flow reserve. In conclusion, all of these intracoronary diagnostic techniques will to some extent play a role in the future of coronary angioplasty. Safety, cost and complexity are some of the factors which will determine the growth potential of each method.

The physiologic meaning of relative coronary flow reserve

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Effect of Antiischemic Therapy on Coronary Flow Reserve and the Pressure-Maximal Coronary Flow Relationship in Anesthetized Swine

The effect of nifedipine (0.5, 1.0, and 2.0 micrograms/kg/min), metoprolol (0.1, 0.5, and 1.0 mg/kg), the beta 1-selective adrenoceptor partial agonist epanolol (10, 50, and 200 micrograms/kg), or equivalent volumes of isotonic saline (n = 6, in each group), on coronary blood flow capacity were studied in anesthetized swine. Intracoronary bolus injections of adenosine (20 micrograms/kg/0.2 ml) were administered without and during three levels of coronary stenosis, prior to and following each dose of drug, to obtain maximal coronary blood flows at different perfusion pressures in the autoregulatory range. Coronary perfusion pressures were varied by partial inflation of a balloon around the left anterior descending coronary artery. Special care was taken that the stenoses not lead to myocardial ischemia. Three indices of coronary blood flow capacity were used: absolute coronary flow reserve (ACFR, the ratio of maximal to resting coronary blood flow), the slope and the extrapolated pressure at zero flow (Pzf) of the pressure-maximal coronary flow (PMCF) relationship, and relative coronary flow reserve (RCFR, the ratio of maximal coronary blood flow with a stenosis to maximal coronary blood flow without a stenosis) at two of the three levels of stenosis. Nifedipine decreased ACFR from 4.5 +/- 1.9 to 1.9 +/- 0.3 (mean +/- SD; p less than 0.05), reflecting in part the increase in resting coronary blood flow. The nifedipine-induced changes in maximal coronary blood flow were not only due to a drop in perfusion pressure, as the slope of the PMCF relationship decreased from 2.27 +/- 0.49 ml/(min.mm Hg) to 1.54 +/- 0.51 ml/(min.mm Hg) (p less than 0.05), and Pzf decreased from 30 +/- 4 mm Hg to 20 +/- 7 mm Hg (p less than 0.05). Consequently, calculated maximal coronary blood flow was attenuated from 114 +/- 31 ml/min to 93 +/- 37 ml/min at 80 mm Hg, but was enhanced from 23 +/- 13 to 37 +/- 24 ml/min at 40 mm Hg coronary perfusion pressure. In concert with the change in the PMCF relationship, RCFR at equivalent severe stenosis increased from 0.33 +/- 0.06 to 0.47 +/- 0.10 (p less than 0.05). No changes were observed with metoprolol, epanolol, or saline. The effect of nifedipine on the PMCF relationship not only provides a mechanism for the drug's antiischemic action, but should also be considered in the interpretation of coronary flow reserve measurements in patients on nifedipine treatment.