Clinical methods to determine coronary flow and myocardial perfusion

In this overview, currently available clinical methods to measure flow in the coronary circulation will be discussed. Methods only applicable in the experimental laboratory or in the anaesthetized patient during cardiac surgery, will not be described. We distinguish between methods that measure global blood flow, and methods that determine regional flow, either at the level of the coronary arteries or at the level of the myocardium. Since it is difficult to measure coronary flow in absolute values, flow reserve is often used as an alternative. Flow reserve is calculated by dividing maximal flow, usually pharmacologically induced, by basal flow. Consequently, assessment of flow reserve requires only measurements of relative changes of coronary flow. The applicability and relative merits and limitations of the techniques are discussed.     

Digital subtraction angiographic assessment of the coronary arteries and coronary flow reserve

Although intravenous digital subtraction angiography was originally intended as a means of performing lessinvasive peripheral angiography, this less invasive approach has not proven feasible for coronary artery studies. Digital imaging has, however, proven helpful for the immediate replay, enhancement and quantification of coronary arteriography and enables the performance of regional blood flow (coronary flow reserve) analysis. Flow analysis is clinically helpful in determining the hemodynamic significance of individual coronary stenoses, which cannot always be assessed even using quantitative stenosis measurements. One method of assessing flow reserve by digital means uses parametric images to display the timing (color coded) and density (intensity coded) of the contrast bolus as it transverses the regional myocardial circulation. Analysis of baseline and hyperemic condition parametric images provides quantitative regional flow reserve information.     

Papavine: The ideal coronary vasodilator for investigating coronary flow reserve? A study of timing,magnitude, reproducibility,and safety of the coronary hyperemic response after intracoronary papaverine

A potent, short-acting vasodilator that induces a maximal hyperemic response of the coronary vascular bed is needed to determine coronary flow reserve. In 12 patients, we measured coronary sinus blood flow by thermodilution over a period of 2 min during which a bolus of 10 mg papaverine was given into the left main coronary artery. This was repeated after 5 min to assess the reproducibility of the changes. The maximal hyperemic response lasted from 24 until 37 sec after papaverine administration. There was no significant difference between the two consecutive hyperemic responses (Student's t-test for paired observations). The mean difference between first and second hyperemic responses at 30 sec was 7.0% (SD ± 6.2%). In conclusion, 10 mg of intracoronary papaverine is a short-lasting and reproducible means of inducing a maximal hyperemic response in the coronary vascular bed and therefore appears to be the ideal agent for investigating coronary flow reserve.     

Intravascular ultrasound findings in patients with abnormal coronary flow reserve after stenting.

A coronary flow reserve (CFR) of 2.0 has been advocated as the endpoint for coronary intervention therapy. Experience shows, however, that CFR does indeed exceed 2.0 in many cases poststenting, while remaining below 2.0 in others. In this study, we assessed the clinical characteristics and IVUS findings of patients whose CFR remained below 2.0 after stent implantation, specifically 16 patients with CFR below 2.0 (22 lesions, 64 +/- 9 years, 4 female), and 102 patients with CFR above 2.0 (112 lesions, mean age 66 +/- 11 years, 22 female). Patient population comprised patients selected for retrospective study, but participants were selected on the basis of matching patient and lesion characteristics. The IVUS findings showed that incidence of calcified lesions and post-PTCA dissection of hard plaque were higher among patients with CFR < 2.0. Further, IVUS-obtained vascular measurements showed post-PTCA area stenosis to be 58.7 +/- 15.2% in the CFR < 2.0 group, and 45.3 +/- 12.5% among CFR > or = 2.0 patients (P < 0.05). These findings indicate that patients with diffuse calcified lesions or high post-PTCA % area stenosis, as determined by IVUS, are more likely to have lower CFR after stenting.     

Effects of atorvastatin on coronary flow reserve in patients with slow coronary flow

BACKGROUND: Statins improve endothelial functioning in patients with coronary artery disease and hypercholesterolemia, while substantially little is known about induced changes in myocardial microcirculation. However, although previous studies have suggested that microvascular abnormalities and endothelial dysfunction is responsible for slow coronary flow (SCF), there is no study investigating possible effects of statins on coronary microvascular function in patients with SCF. HYPOTHESIS: We prospectively investigated the effects of short-term lipid-lowering therapy with atorvastatin on coronary flow reserve (CFR) reflecting coronary microvascular function in patients with SCF assessed by transthoracic Doppler echocardiography (TTDE). METHODS: In an open clinical trial, CFR was studied in 20 subjects with SCF. TTDE was used to assess CFR at baseline as well as after 8 weeks of atorvastatin therapy. Coronary flow was quantified according to TIMI frame count (TFC). Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. RESULTS: CFR was independently correlated with TFC. After 8 weeks of atorvastatin therapy, CFR values increased significantly (1.95 +/- 0.38 vs. 2.54 +/- 0.56, (p < 0.001). No change in hemodynamic parameters was noted during the entire study. The improvement in CFR was not correlated to the amount of lipid-lowering effect of atorvastatin. CONCLUSIONS: These findings suggest that short-term lipid-lowering therapy with atorvastatin improved CFR, which reflects coronary microvascular functioning in patients with SCF.     

基于冠状动脉CT的血流储备分数诊断冠心病的价值和临床研究进展

冠状动脉CT血管成像(CCTA)可以评估冠状动脉的解剖学狭窄,但不能准确判断冠状动脉狭窄尤其临界病变是否可引起相应的心肌缺血。血流储备分数(FFR)是评估冠状动脉狭窄是否引起功能性缺血的金标准,但属于有创性检查,且费用昂贵,临床上尚未普及应用。基于冠状动脉CT的血流储备分数(FFRCT)实现了无创条件功能学和解剖学的结合,对冠心病的诊断具有重要的意义,本文就FFRCT诊断冠心病的价值和临床研究进展作一综述。     

应用经胸冠状动脉血流显像技术评价支架术前后冠脉血流储备

目的采用经胸多普勒超声心动图冠状动脉血流显像技术观察支架术前后冠状动脉血流速度的变化,评价其对冠状动脉血流储备（CFR）的影响。方法22例冠心病患者(男18例,女4例),平均年龄（53.2±6.7）岁。对狭窄的冠状动脉行经皮冠状动脉腔内成形术（PTCA）后各置入一枚支架。分别于木前、术后72h内采用经胸多普勒冠状动脉血流显像技术记录狭窄远端静息舒张期血流峰速(r-Vd)、注射潘生丁及等长握力实验时最大舒张期血流峰速(d-Vd)及CFR。结果22例患者行支架术均获成功,狭窄率由术前(83.5±8.9)%,降至术后(5.2±9)%(P<0.05)。20支冠脉获得理想多普勒频谱（检出率90.9％）;支架术后r-Vd较术前r-Vd有增加趋势,但无统计学意义;术后静脉注射潘生丁后最大d-Vd及CFR均较术前明显增加［（0.92±0.22)m/svs(0.52±0.18)m/s,2.94±1.16vs1.88±0.40,P均<0.01］。30％患者术后CFR仍<2.0,此组与CFR≥2.0患者组比较,支架术后r-Vd明显增高［(0.45±0.19)m/svs(0.27±0.12)m/s,P<0.05］。少数患者(约18%,4／22)术前出现心绞痛,头昏等不适,静注氨茶碱或(和)含化硝酸甘油可迅速缓解。结论支架术能明显增加冠状动脉血流储备。采用经胸多普勒冠脉血流显像技术结合潘生丁、握力试验是一可行的无创性评价冠心病患者冠脉血流储备及介入治疗疗效的新方法。     

瑞舒伐他汀对冠状动脉慢血流患者冠状动脉贮备功能和超敏C反应蛋白的影响

目的:探讨长期瑞舒伐他汀治疗对冠状动脉慢血流患者冠脉贮备功能(CFR)和超敏C反应蛋白(hsCRP)的影响。方法:选择冠状动脉造影正常但存在冠脉慢血流的患者48例,所有患者随机分为试药组和对照组,对照组(22例)予常规治疗,试药组(26例)在常规治疗基础上加用瑞舒伐他汀20 mg/d,治疗期为6个月。治疗前后测定两组患者的血脂,hsCRP,利用腺苷负荷超声记录左前降支远端血流频谱评评价CFR。结果:经过6个月瑞舒伐他汀的治疗后,试药组总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)较对照组明显下降,[TC:(3.2±0.9)mmol/Lvs.(5.4±1.2)mmol/L,P<0.05;LDL-C:(2.1±0.7)mmol/L vs.(3.4±0.8)mmol/L,P<0.05]。hsCRP较对照组明显下降[(2.1±1.4)mg/L vs.(3.7±2.1)mg/L,P<0.05]。试药组静息冠脉血流速度(bCFV)较对照组和治疗前显著下降[(21±6)cm/s vs.(26±5)cm/s和(21±6)cm/s vs.(25±7)cm/s,P<0.05],而最大冠状动脉扩张状态hCFV较对照组和治疗前增加[(71±9)cm/s vs.(56±8)cm/s和(71±9)cm/s vs.(56±10)cm/s,P<0.05],冠状动脉血流储备CFR较对照组和治疗前明显增加[(3.2±0.6)cm/s vs.(2.1±0.5)cm/s和(3.2±0.6)cm/s vs.(2.2±0.4)cm/s,P<0.05)]。结论:冠状动脉慢血流患者经过瑞舒伐他汀治疗可以有效改善冠脉贮备功能。     

Practice and potential pitfalls of coronary pressure measurement

Guidewire‐based coronary pressure measurement has emerged over the last years as a promising approach in the invasive assessment of coronary artery disease. It enables calculation of fractional flow reserve (FFR) which closely relates distal coronary pressure to myocardial blood flow during maximal arteriolar vasodilation. Coronary pressure measurement and FFR provide important information, both for decision making in diagnostic angiography and for monitoring and evaluating coronary interventions. In this review, the practical set‐up of coronary pressure measurement in the catheterization laboratory is discussed step‐by‐step, special attention is given to potential pitfalls and how to avoid them, and the interpretation of coronary pressure measurement in a variety of pathologic conditions is clarified. Cathet. Cardiovasc. Intervent. 49:1–16, 2000. © 2000 Wiley‐Liss, Inc.     

Normal coronary flow reserve in patients with mitral valve prolapse, a positive exercise test and normal coronary arteries

We studied 12 patients (eight females and four males), ages30–46 years, with echocardiographically documented mitralvalve prolapse and clinical suspicion of coronary artery disease,based on a history of chest pain (five patients), angina-likepain (three patients), a positive exercise stress electrocardiogram(12 patients) and a focally positive thallium-201 stress perfusionscan (three patients), who were referred for cardiac catheterizationand found to have normal coronary arteries. Ten patients withoutevidence of heart disease served as controls. In all mitralvalve prolapse patients, coronary flow velocity reserve wasdetermined successively in the left anterior descending, leftcircumflex and right coronary arteries as the ratio of the maximun(after intracoronary papaverine) to the resting mean coronaryflow velocity. Coronary flow reserve values were fairly similarin the mitral valve prolapse and control patients; all 12 mitralvalve prolapse patients had normal coronary flow reserve (3.5)in all three coronary arteries with no significant differencesamong the arteries tested Mean values ± 1 standard deviationof the coronary flow reserve (mitral valve prolapse vs controlpatients) were 4.7 ± 0.5 vs 4.6 ± 0.6 for theleft anterior descending, 4.6 ± 0.4 vs 4.6 ± 0.3for the left circumflex and 4. ± 0.4 vs 4.4 ±0.5 for the right coronary artery (all P=non-significant). Thesubsets of mitral valve prolapse patients with different clinical‘ischaemic’ manifestations were similar in termsof the calculated coronary flow reserve in all three major epicardialcoronary arteries. In conclusion, this study demonstrated that an inadequate regionalcoronary flow reserve does not account for the clinical manifestationsof myocardial ischaemia and positive exercise tests in patientswith mitral valve prolapse and normal coronary arteries.     

Normal coronary flow reserve in patients with mitral valve prolapse, a positive exercise test and normal coronary arteries

We studied 12 patients (eight females and four males), ages30–46 years, with echocardiographically documented mitralvalve prolapse and clinical suspicion of coronary artery disease,based on a history of chest pain (five patients), angina-likepain (three patients), a positive exercise stress electrocardiogram(12 patients) and a focally positive thallium-201 stress perfusionscan (three patients), who were referred for cardiac catheterizationand found to have normal coronary arteries. Ten patients withoutevidence of heart disease served as controls. In all mitralvalve prolapse patients, coronary flow velocity reserve wasdetermined successively in the left anterior descending, leftcircumflex and right coronary arteries as the ratio of the maximun(after intracoronary papaverine) to the resting mean coronaryflow velocity. Coronary flow reserve values were fairly similarin the mitral valve prolapse and control patients; all 12 mitralvalve prolapse patients had normal coronary flow reserve (3·5)in all three coronary arteries with no significant differencesamong the arteries tested Mean values ± 1 standard deviationof the coronary flow reserve (mitral valve prolapse vs controlpatients) were 4·7 ± 0·5 vs 4·6± 0·6 for the left anterior descending, 4·6± 0·4 vs 4·6 ± 0·3 for theleft circumflex and 4· ± 0·4 vs 4·4± 0·5 for the right coronary artery (all P=non-significant).The subsets of mitral valve prolapse patients with differentclinical ‘ischaemic’ manifestations were similarin terms of the calculated coronary flow reserve in all threemajor epicardial coronary arteries. In conclusion, this study demonstrated that an inadequate regionalcoronary flow reserve does not account for the clinical manifestationsof myocardial ischaemia and positive exercise tests in patientswith mitral valve prolapse and normal coronary arteries.     

Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries

BACKGROUND: Epicardial adipose tissue expresses adiponectin protein, and its expression is significantly lower in patients with severe coronary artery disease (CAD) than in those without CAD. Transcoronary adiponectin levels are significantly decreased in nondiabetic but not in diabetic patients with CAD. Adiponectin is also an important adipocytokine that is linked to insulin resistance and reduces coronary microvascular function. HYPOTHESIS: Adiponectin may play a significant role in the localized coronary circulation. The present study examines the local dynamics of adiponectin in the coronary circulation in nondiabetic individuals with normal coronary arteries and the relationship between adiponectin and coronary microvasculature function. METHODS: We examined 22 consecutive nondiabetic patients whose coronary arteries were angiographically normal. Plasma levels of adiponectin were measured in blood samples that were simultaneously collected from the orifice of the left coronary artery (LCA) and the great cardiac vein (GCV). To evaluate the function of the coronary microcirculation, we measured coronary flow velocity at maximal hyperemia using a Doppler wire. Coronary flow reserve (CFR) was obtained from the ratio of hyperemia to the baseline coronary flow velocity. RESULTS: Plasma adiponectin levels in the GCV (median 6.95 microg/ml) were significantly higher than those in the LCA (median 6.60 microg/ml, p < 0.0005). The difference in plasma adiponectin levels between GCV and LCA significantly correlated with CFR (R = 0.451, p < 0.05). CONCLUSIONS: Adiponectin is locally produced in the coronary circulation. This protein may participate in modulating the coronary circulation of nondiabetic patients with angiographically normal coronary arteries.     

Detection of impaired coronary flow reserve in coronary artery disease using transthoracic echocardiographic assessment of coronary sinus blood flow

In order to establish whether coronary flow reserve (CFR) can be measured by transthoracic echocardiography (TTE) with pulse wave Doppler echocardiography, 14 patients with coronary artery disease (CAD) and 12 normal subjects were studied. Coronary sinus blood flow was measured at rest and 2 minutes after intravenous injection of 0.56 mg/kg dipyridamole (DP). CFR was calculated as the DP to rest flow ratio. Patients with CAD were found to have significantly decreased CFR when compared to normal subjects. These findings suggest that TTE may be useful in diagnosing CAD.     

Value of exercise radionuclide ventriculography and thallium-201 scintigraphy in evaluating successful coronary angioplasty: comparison with coronary flow reserve, translesional gradient and percent diameter stenosis

Assessment of percutaneous transluminal coronary angioplasty(PTCA) by early radionuclide exercise test was evaluated for11 arteries undergoing a successful procedure. Exercise thallium-201(Tl-201) and radio-nuclide ventriculography (RNV) were performedwithin 3 days before and after PTCA and compared to % diameterstenosis, % translesional gradient and regional coronary flowreserve (CFR) determined by digital coronary angiography. Primarysuccess of the procedure was gauged by reduction in % stenosisfrom 80 ± 12% to 31 ± 12% (residual stenosis <50% in all cases) and reduction in % gradient < 25% in allcases). Before PTCA, Tl-201 and/or RNV were abnormal in allcases. After PTCA, radionuclide exercise tests improved butremained abnormal in 4 instances. No relationship was foundbetween residual % gradient or stenosis and pathological Tl-201or RNV following PTCA, but abnormal tests were observed among4 out of the 5 vessels with the lowest CFR ( < 1.69). Inone case CFR remained depressed despite good angiographic, hemodynamicand scintigraphic results, this patient had unstable anginabefore the procedure. Among patients with stable symptoms, CFRof arterial distributions with positive Tl-201 or RNV afterPTCA was significantly lower than that with negative tests (1.58± 0.05 as compared to 1.90±0.25, P<0.02). Earlyradionuclide stress tests results thus reflect the physiologicimprovement of coronary circulation. They may reflect the persistenceof coronary flow abnormalities despite the relief of the epicardialstenosis.     

Effects of smoking on coronary blood flow velocity and coronary flow reserve assessed by transthoracic Doppler echocardiography

BACKGROUND: Smoking is a well-known risk factor for cardiovascular disease. Coronary blood flow velocity (CFV) can be measured directly with transthoracic Doppler echocardiography (TTDE) which is conducted immediately after smoking. PURPOSE: The purpose of this study was to evaluate the chronic and acute effects of smoking on coronary blood flow and coronary flow reserve (CFR) by the use of TTDE. METHODS: Healthy volunteers (11 smokers and 9 nonsmokers) with a mean age of 27 +/- 3 years were included. Smoking was abstained for at least 4 hours before the study. CFV was measured at the distal left anterior descending coronary artery by TTDE at baseline and during intravenous adenosine infusion (140 microg/kg per minute) in all participants. For smokers, CFV was measured immediately after consecutively smoking two cigarettes and during adenosine infusion. RESULTS: CFR and coronary vascular resistance index (CVRI) showed no significant difference between nonsmokers and smokers (CFR: 3.5 +/- 0.8 vs 3.6 +/- 0.6, P = ns, CVRI: 0.28 vs 0.28, P = ns) at baseline. CFR significantly decreased (3.6 +/- 0.6 to 2.8 +/- 0.7, P = 0.008) and CVRI markedly increased (0.28 to 0.35, P = 0.012) after smoking. CONCLUSION: After 4 hours of abstinence from smoking, CFR and CVRI in smokers were similar to those of nonsmokers. However, consecutively smoking two cigarettes acutely reduced CFR and increased CVRI. These findings suggested that smoking could reduce coronary blood flow immediately, even in healthy people.     

血流储备分数指导冠心病介入治疗的研究

目的:讨论血流储备分数(FFR)指导冠心病介入治疗(PCI)的疗效.方法:入选2011年8月至2013年8月共126例需作介入治疗的冠心病患者,根据FFR分组,实验组:FFR≥0.8,63例,行延迟PCI+强化药物治疗(OMT)],共有77处病变;对照组:FFR＜0.8,63例,行PCI+ OMT,共有92处病变.所有患者在术后第12、24、36个月进行电话随访,在PCI术后12个月进行冠脉造影的复查.观察主要心血管不良事件(MACE).结果:实验组平均血管狭窄率明显低于FFR＜0.8组[(49.5±5.3)％比(75.9±10.1)％];术后经过(27.1±8.8)个月的随访,实验组有4例(6.4％)发生MACE事件:1例(1.6％)死亡,与对照组的MACE事件(14.3％,9/63),死亡率4.8％ (3/63)无显著差异,P＞0.05.结论:对于血流储备分数(FFR)≥0.8有手术指征的冠心病患者行延迟PCI+OMT是安全有效的.     

Clinical value of digital radiographic coronary quantification: comparison with visual assessment and coronary flow reserve.

The value of quantitative assessment of coronary artery dimensions at the site of the most critical coronary stenosis was assessed by comparison with the correspondent reactive hyperaemia as measured by digital subtraction angiography and with the functional results. Thirty-two coronary lesions were analysed and flow reserve data were obtained in an additional 11 vascular distributions without coronary obstruction in 19 patients. Minimal diameter less than 1.25 mm and minimal area less than 1.5 mm2 at the site of the stenosis best separated vascular distributions with inadequate hyperaemic response from those with sufficient reactive hyperaemia (chi 2 = 19.57; P less than 0.0001). Identification of lesion severity based on videodensitometric percentage area stenosis greater than 70% or percentage diameter stenosis greater than 50% yielded similar but poorer results (respectively chi 2 = 14.53; P less than 0.001 and chi 2 = 10.29; P less than 0.005). Additionally, when visually determined percentage stenosis was compared to the quantitatively assessed value, only a fair correlation was observed (r = 0.74), with visual overestimation of lesion severity by an average of 11.1 +/- 9.8% (mean +/- SD). Reactive hyperaemia in vessels with coronary obstruction could be described from minimal coronary dimensions by a quadratic equation but did not correlate closely in this patient population (r = 0.54 with minimal diameter and r = 0.58 with minimal area).(ABSTRACT TRUNCATED AT 250 WORDS)