冠心病血流储备分数的研究进展及临床应用

如今血流储备分数（FFR）被认为是对冠状动脉狭窄病变进行功能评价的＂金标准＂,是指导冠状动脉血运重建策略的有力工具。FFR是一项简单、可靠、重复性良好的检查方法。多项研究表明,FFR指导的冠状动脉血运重建能够改善患者的预后,减少支架植入数目及医疗花费。近年来由FFR衍生出的一些新技术为狭窄病变的功能评估提供了更多可能。本文对FFR的研究进展及临床应用进行了综述。     

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.     

A simple thermodilution technique to assess coronary endothelium-dependent microvascular function in humans: validation and comparison with coronary flow reserve.

AIMS: To validate a novel method for assessment of coronary endothelium-dependent microvascular function and compare this index with the adenosine-derived coronary flow reserve (CFR). METHODS AND RESULTS: We validated use of intra-coronary pressure wire-derived thermodilution to assess changes in coronary flow compared to Doppler flow-wire/quantitative coronary angiography- (QCA) derived data in response to the endothelial agonist substance-P (endothelium-dependent response). There was a close correlation between Doppler/QCA- and thermodilution-derived assessment of endothelium-dependent microvascular function (r = 0.76; P < 0.001). Next, pressure wire-based thermodilution was employed to sequentially compare CFR (hyperaemia achieved with adenosine-140 microg/kg/mL) with changes in coronary flow in response to substance-P (20 pmol/min intra-coronary infusion; 2 min) in 65 unobstructed coronary arteries. There was no correlation between CFR and coronary endothelium-dependent microvascular response (r = 0.08; P = 0.50). Both indices were in turn compared with clinical markers of endothelial dysfunction, namely Framingham risk score (FRS-a marker for cardiovascular risk factor clustering, hence an indirect clinical measure of endothelial dysfunction) and presence/absence of diabetes. Patient's FRS correlated with coronary endothelium-dependent microvascular response (r = -0.48; P < 0.001), but not with CFR (r = 0.14; P = 0.25). Diabetic patients had greater endothelial dysfunction than non-diabetics (P < 0.001) whereas CFR was not influenced by diabetes (P = 0.10). CONCLUSION: A simple pressure wire-based thermodilution technique can be used to assess coronary endothelium-dependent microvascular function. Adenosine-derived CFR does not adequately interrogate the endothelium-dependent component of coronary microvascular function.     

Clinical applications of fractional flow reserve in bifurcation lesions

Percutaneous coronary intervention (PCI) for coronary bifurcation lesions has been associated with lower procedural success rates and worse clinical outcomes compared with PCI for simple coronary lesions. Angiographic evaluation alone is sometimes inaccurate and does not reflect the functional significance of bifurcation lesions. The fractional flow reserve (FFR) is an easily obtainable, reliable, and reproducible physiologic parameter. This parameter is epicardial lesion specific and reflects both degree of stenosis and the myocardial territory supplied by the specific artery. Recent studies have shown that FFR-guided provisional side branch intervention strategy for bifurcation lesions is feasible and effective and can reduce unnecessary complex interventions and related complications. However, an adequate understanding of coronary physiology and the pitfalls of FFR is essential to properly use FFR for PCI of complex bifurcation lesions.     

Sténose aortique et lésions coronaires : la fractional flow reserve (FFR) est-elle valide ?

A 54-year-old woman was hospitalized for an acute pulmonary oedema revealing a severe aortic stenosis (AS) associated with an aortic aneurysm and a left ventricular hypertrophy (LVH). The coronary angiography found an equivocal left main lesion. Fractional flow reserve (FFR) showed hemodynamic significance (FFR = 0.78) and optical coherence tomography confirmed this result with a minimal lumen area of 4.9 mm². FFR-guided percutaneous intervention is reported to improve outcome in patients with stable coronary disease. However, only few data are available in cases of AS. In this condition, secondary LVH is associated with microcirculatory dysfunction, which interferes with optimal hyperemia. An elevated right atrial pressure could also modify FFR measurement. This risk of underestimation of a coronary lesion in patients with severe AS has to be taken into consideration in clinical practice.     

One-year outcome of patients submitted to routine fractional flow reserve assessment to determine the need for angioplasty.

AIMS: In patients submitted to coronary angiography, fractional flow reserve (FFR) assessment by a pressure wire can be used to guide the decision for revascularization. Routine application of FFR assessment and 1-year outcome of patients are poorly documented. The aim of this study was to report a 4-year single-centre experience where the use of FFR for decision making in equivocal lesions is encouraged. METHODS AND RESULTS: A prospective registry was designed to collect clinical and angiographic characteristics, as well as 1-year clinical follow-up for all patients submitted to FFR assessment. The decisional cut-off point for revascularization was 0.80. Over a 4-year period, out of 6415 coronary angiographies, FFR was measured in 407 (6.3%) patients (469 lesions). FFR was assessed through 4 or 5 Fr diagnostic catheters in 330 (81%). Median FFR value was 0.87 (0.80; 0.93). On the basis of FFR results, 271 (67%) patients were treated with medical therapy alone. A subset of 71 (17%) patients were not treated in accordance with the results of FFR. All patients but four (i.e. 99%) had 1-year clinical follow-up. Three hundred and forty four (85%) were free from clinical event, six (1.5%) patients died, five (4%) had an acute coronary syndrome, and 20 (5%) underwent target-vessel revascularization. Event-free survival was comparable in patients with vs. without revascularization (0.94 +/- 0.02 and 0.93 +/- 0.01, respectively). Patients had significantly better 1-year outcome when treated in accordance with the results of the FFR assessment. CONCLUSION: In routine practice, FFR assessment during diagnostic angiography was performed in 6.3%. On the basis of FFR, two-thirds of patients with 'intermediate' lesions were left unrevascularized, with a favourable outcome, when FFR was above 0.80. These data suggest that routine use of FFR during diagnostic catheterization is feasible, safe, and provide help to guide decision making.     

Adoption and patterns of use of invasive physiological assessment of coronary artery disease in a large cohort of 40 821 real-world procedures over a 12-year period

Introduction and ObjectivesUse of invasive physiological assessment in patients with coronary artery disease varies widely and is perceived to be low. We aimed to examine adoption rates as well as patterns and determinants of use in an unselected population undergoing invasive coronary angiography over a long time frame.MethodsWe retrospectively determined the per-procedure prevalence of physiological assessment in 40 821 coronary cases performed between 2007 and 2018 in two large-volume centers. Adoption was examined according to procedure type and patient- and operator-related variables. Its association with relevant scientific landmarks, such as the release of clinical trial results and practice guidelines, was also assessed.ResultsOverall adoption was low, ranging from 0.6% in patients undergoing invasive coronary angiography due to underlying valve disease, to 6% in the setting of stable coronary artery disease (CAD); it was 3.1% in patients sustaining an acute coronary syndrome. Of scientific landmarks, FAME 1, the long-term results of FAME 2 and the 2014 European myocardial revascularization guidelines were associated with changes in practice. Publication of instantaneous wave-free ratio (iFR) trials had no influence on adoption rates, except for a higher proportion of iFR use. In 42.9% of stable CAD patients undergoing percutaneous coronary intervention there was no objective non-invasive evidence of ischemia, nor was physiological assessment performed. Younger operator age (4.5% vs. 4.0% vs. 0.9% for ages <40, 40-55 and >55 years, respectively; p<0.001) and later time of procedure during the day (2.9% between 6 and 8 p.m. vs. 4.4% at other times) were independent correlates of use of invasive physiology.ConclusionsOur study confirms the low use of invasive physiology in routine practice. The availability of resting indices did not increase adoption. Strategies are warranted to promote guideline implementation and to improve patient care and clinical outcomes.     

Quantificação do fluxo sanguíneo miocárdico por tomografia por emissão de positrões – Atualização

Cardiovascular disease is the leading cause of death worldwide and ischemic heart disease is the most frequent etiology, with high economic costs for both treatment and diagnosis. Over the past two decades, the assessment of patients with this disease has undergone various changes, with cardiac positron emission tomography (PET) emerging as a powerful and versatile imaging exam for diagnosis and risk stratification of these patients. This review aimed to assess the utility of this exam, particularly through quantification of myocardial blood flow and myocardial flow reserve in the diagnosis and risk stratification of coronary artery disease. Compared to other imaging methods, measurement of these parameters by cardiac PET provides a better characterization of coronary artery disease, with particular value in microvascular and balanced multivessel disease.     

冠状动脉内注射罂粟碱后血压和心电图改变

８８例患者，左、右冠状动脉内注射罂粟碱后主动脉收缩压、舒张压和平均压减低，心率增快和ＱＴ间期延长。左冠状动脉内注射罂粟碱后（８８例）．２例（２．３％）ＳＴ段改变，４５例（５１．１％）Ｔ波改变，１４例（１５．９％）ＳＴ－Ｔ波改变，２例（２．３％）多形性室速。右冠状动脉内注射罂粟碱后（５２例）．１例（１．９％）ＳＴ段改变，３３例（６３．５％）Ｔ波变化，１２例（２３．１％）ＳＴ－Ｔ波改变，１例（１．９％）多形性室速。故冠状动脉内注射罂粟碱作冠状动脉储备测定须十分谨慎。     

Normal Coronary Arteries: Clinical Implications and Further Classification

Abstract The term chest pain with normal coronary arteries encompasses a large number of different cardiac pathophysiological abnormalities, including impairment of coronary flow reserve, endothelial dysfunction, and early atherosclerosis that, in most cases, cannot be readily differentiated one from the other.To study early coronary atherosclerosis, physicians must look beyond contrast filled arteries (so called lumenology). Angiograms cannot evaluate the vessel wall, plaque distribution and composition or other morphology. Plaques are often angiographically not visible due to their small size and compensatory enlargement (outward remodeling) of the coronary arteries. As a result, the search for an underlying atherosclerotic process remains ongoing. Available clinical studies showed that many patients with chest pain and normal angiography have early atherosclerosis as documented by intravascular ultrasound imaging, reduced coronary flow reserve and coronary endothelial dysfunction. Additional studies showed that patients presenting with normal coronary angiography have recurrent coronary events at long-term follow up.Research to determine if improved diagnosis and treatment of quantitatively low degrees of atherosclerosis lead to improved outcomes of patients with normal angiography should be undertaken.     

Cardiac magnetic resonance perfusion imaging for the functional assessment of coronary artery disease: a comparison with coronary angiography and fractional flow reserve.

AIMS: Cardiac magnetic resonance perfusion imaging (CMRI) is a promising technique for non-invasive measurement of myocardial perfusion reserve. Fractional flow reserve (FFR) is an established invasive method for functional assessment of coronary artery disease (CAD). To prospectively assess the diagnostic value of CMRI for the detection of haemodynamically significant coronary lesions, compared with coronary angiography (CA) and FFR. METHODS AND RESULTS: Forty-three patients with suspected or known CAD underwent CA, CMRI, and FFR measurement. First pass magnetic resonance perfusion examination was performed during hyperaemia (140 microg/kg/min adenosine over 6 min) and at rest. One hundred and twenty-nine perfusion territories were assessed by semi-quantitative evaluation of signal intensity-time curves using the myocardial perfusion reserve index (MPRI) [upslope(stress(corrected))/upslope(rest(corrected))]. Perfusion territories were categorized as normal (coronary stenosis < or = 50%), intermediate (stenosis > 50% and FFR > 0.75), or severe (stenosis > 50% and FFR < or = 0.75 or total occlusion). MPRI values (+/-SD) were significantly different between the three categories [normal, 2.2 +/- 0.5 vs. intermediate, 1.8 +/- 0.5 (P = 0.005) and intermediate vs. severe, 1.2 +/- 0.3 (P < 0.001)]. An MPRI cut-off value of 1.5 (derived from receiver operating characteristics analysis) distinguished haemodynamically relevant (severe) from non-relevant (normal and intermediate) stenoses with a sensitivity of 88% (CI 74-100%) and a specificity of 90% (CI 84-96%). CONCLUSION: In contrast to earlier studies that compared CMRI with morphological examination (CA) alone, the present study compared CMRI with CA plus a standard invasive functional assessment (FFR) and demonstrated that CMRI is able to distinguish haemodynamically relevant from non-relevant coronary lesions with a high sensitivity and specificity and may therefore contribute to clinical decision-making.     

Validation of noninvasive assessment of coronary flow velocity reserve in the right coronary artery. A comparison of transthoracic echocardiographic results with intracoronary Doppler flow wire measurements.

AIMS: Assessment of coronary flow velocity reserve (CFR) noninvasively using transthoracic Doppler echocardiography (TDE) is validated for the left anterior descending artery only. We evaluated the feasibility and reproducibility to assess CFR using TDE in the right coronary artery, and compared the results with intracoronary Doppler flow wire (DFW) measurements. METHODS AND RESULTS: Introduction of a modified apical 2-chamber view allows visualization of the posterior descending branch of the right coronary artery (RPD). 42 consecutive patients (31 men, mean age 61+/-10) with suspected coronary artery disease scheduled for coronary angiography underwent CFR assessment using TDE in fundamental imaging mode; the results were compared with DFW measurements. CFR could be taken noninvasively in 81% (34/42); in case of right dominant- or balanced coronary circulation type success rate was significantly higher (87%; 33/38) than in case of left dominant coronary circulation (25%; 1/4). Correlation between echocardiographically and intracoronary derived CFR results was significant (r=0.85, P<0.0001), as well as reproducibility (r=0.94, P<0.0001) and interobserver variability (r=0.78, P<0.0001). CONCLUSION: Coronary flow reserve assessed in the peripheral RCA by TDE concurs very closely with intracoronary Doppler flow wire CFR results. This new approach allows feasible, accurate and reproducible measurement of CFR in the RCA.     

Systemic inflammation is related to coronary microvascular dysfunction in obese patients without obstructive coronary disease

Background and AimsObesity, systemic inflammation and changes in the heart functions are associated with increased cardiovascular risk. This study aimed to investigate coronary microvascular dysfunction as an early marker of atherosclerosis in obese patients without any evidence of cardiovascular disease.Methods and results86 obese subjects (aged 44 ± 12 years, body mass index (BMI) 41 ± 8 kg m⁻²), without evidence of heart disease, and 48 lean controls were studied using transthoracic Doppler echocardiography for detecting coronary flow reserve (CFR). A value of CFR ≤ 2.5 was considered abnormal. We measured interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin in all patients. Patients with abnormal CFR underwent coronary multislice computed tomography (MSCT) in order to exclude an epicardial stenosis. CFR in obese subjects was lower than in lean subjects (3.2 ± 0.8 vs. 3.7 ± 0.7, p = 0.02) and was abnormal in 27 (31%) obese patients and in one (2%) control (p < 0.0001). All subjects with abnormal CFR showed no coronary stenosis at MSCT. At multivariable analysis, IL-6 and TNF-α were the only determinants of CFR (p < 0.02 and p < 0.02, respectively). At multivariable logistic regression analysis, IL-6 and TNF-α were the only determinants of CFR ≤ 2.5 (p < 0.03 and p < 0.03, respectively).ConclusionsCFR is often reduced in obese subjects without clinical evidence of heart disease, suggesting a coronary microvascular impairment. This microvascular dysfunction seems to be related to a chronic inflammation mediated by adipocytokines. Our findings may explain the increased cardiovascular risk in obesity, independently of BMI.     

在静息血流无限制的慢性冠状动脉狭窄中静息心肌收缩功能与血流储备的关系

目的 :评价静息心肌收缩功能与血流储备的关系。　　方法 :以安放“水膨胀”式缩窄器的方法建立 11只慢性多支冠状动脉 (冠脉 )狭窄闭胸犬。术后 7～ 10天在静息状态下以二维超声心动图测定室壁增厚百分率 (% WT) ,同时以放射性微球测定心肌血流量 (MBF)和 MBF储备。　　结果 :在 40个心室壁运动异常的心肌节段与 42个心室壁收缩功能正常的心肌节段之间 ,静息心室壁和心内膜下血流均无明显差异 ,但后者的心室壁和心内膜下血流储备均明显低于前者。静息状态 % WT与 MBF储备密切相关 (P<0 .0 0 1)。　　结论 :在静息状态血流无限制的慢性冠脉狭窄犬 ,% WT异常心肌节段的 MBF储备明显降低 ,静息状态 % WT与MBF储备密切相关 ,表明局部收缩功能异常可能是由于反复“需氧增多”性心肌缺血所致。     

侵入性冠状动脉生理功能检测指标综述

目前临床上主要根据血管造影结果评估冠状动脉情况,但血管造影对于冠状动脉复杂病变如临界病变、偏心性病变和弥漫性病变的评估尚有局限性,而对冠状动脉生理功能的评估可很好地解决这些问题,有助于临床医师更准确地诊断和治疗。为此,本文总结了临床导管室目前评估冠状动脉生理功能的主要侵入性检测指标,以使读者客观地了解这些指标的意义。     

Integrated coronary physiology in percutaneous intervention: a new paradigm in interventional cardiology

Coronary angiography has provided an unrivalled appreciation of coronary anatomy fostering a far greater appreciation of the extent of atherosclerotic disease. However, the subjectivity of coronary angiography at determining the extent of plaque has been exposed with IVUS. Indices of coronary physiology have provided valuable adjunctive information as to the physiological importance of specific lesions. Fractional flow reserve is an established method for evaluating the significance of epicardial stenoses. Fractional flow reserve guided percutaneous coronary intervention is associated with improved outcomes when compared to a conventional angiographic guided strategy, particularly in intermediate lesions. The use of coronary physiology in the cath lab represents a new avenue to guide appropriate patient specific revascularisation strategies. This review examines the theory and evidence for fractional flow reserve and its use in percutaneous coronary intervention.     

Reduced coronary flow reserve in the coronary sinus is a predictor of hemodynamically significant stenoses of the left coronary artery territory.

AIM AND METHODS: The role of transesophageal Doppler assessment of coronary flow reserve (CFR) in the coronary sinus (CS) in the diagnostics of significant left coronary artery (LCA) stenoses was studied in 65 CAD patients with angiographically proven >50% stenotic atherosclerosis of the LCA territory (38--with isolated left anterior descending artery (LAD) or left circumflex artery (Cx) stenosis; 27--with both LAD and Cx stenoses) and 31 healthy volunteers (all men). Dipyridamole was used as a stress agent. The antegrade phase of coronary flow in the CS moving into the right atrium was analysed. CFR in the CS was calculated in two ways: (1) as ratio of hyperemic to baseline peak antegrade flow velocity (CFRp); (2) as ratio of hyperemic to baseline volumetric blood flow velocity (CFRv). The level of CFR <2.0 in both ways of calculation was diagnosed as reduced. RESULTS: CAD patients compared with healthy volunteers had significantly lower CFRp (1.51+/-0.44 and 2.57+/-0.79; p<0.001) and CFRv (2.21+/-1.18 and 5.43+/-2.83; p < 0.001) in the CS. CFRp <2.0 in the CS was a predictor of significant stenoses of the LCA with sensitivity of 89% and specificity of 76%, while CFRv <2.0 was a predictor of significant stenoses of the LCA with sensitivity of 49% and specificity of 97%. CFRp <2.0 in the CS was registered in 96% of CAD patients with two-vessel lesion and in 84% of CAD patients with one-vessel lesion, while CFRv <2.0 in the CS was revealed in 85% of CAD patients with two-vessel lesion and only in 26% of CAD patients with one-vessel lesion. Sensitivity and specificity of CFRv <2.0 in the CS in the diagnostics of significant two-vessel lesion of the LCA were 85% and 84%, respectively. CONCLUSIONS: Thus, the reduced CFR in the CS is a sensitive and specific predictor of LCA stenoses. A decrease of both CFRp <2 and CFRv <2.0 in the CS is a predictor of significant two-vessel lesion of the LCA, while a decrease of only CFRp <2.0 in the CS is a predictor of significant one-vessel lesion of the LCA.     

Validation of coronary flow reserve measurements by thermodilution in clinical practice.

BACKGROUND: Coronary flow reserve (CFR) and fractional flow reserve (FFR) provide complementary information on the coronary circulation. Using a pressure wire, it is possible to calculate CFR by thermodilution (CFR(thermo)), so that FFR and CFR can be measured with a single guide wire. The present multicentric study was performed to compare the feasibility of CFR(thermo)obtained with an improved algorithm and a standardized injection technique and its agreement with Doppler-derived CFR (CFR(Doppler)). METHODS AND RESULTS: In 86 patients with coronary artery disease recruited during 1 week in eight centres FFR, CFR(thermo)and CFR(Doppler)were measured. FFR could be obtained in all patients (100%). An optimal CFR(Doppler)could be obtained in 69% of the patients. CFR(thermo)could be obtained in 97% of the patients. A significant correlation was found between CFR(Doppler)and CFR(thermo)(r=0.79, P<0.0001) but CFR(thermo)tended to be higher than CFR(Doppler). CONCLUSIONS: In a setting close to 'real world' practice, this multicentric study confirms the feasibility and reliability of thermodilution-derived CFR. In addition, the safety and the swiftness of assessing FFR and CFR with one single guide wire makes the latter a unique clinical tool for the evaluation of the coronary circulation.     

冠状动脉CT血管成像狭窄评分定量评估缺血相关病变的临床价值

目的:分析冠状动脉CT血管成像狭窄评分(CCTA-SS)在定量评估缺血相关病变中的临床价值.方法:回顾性分析经冠状动脉CT血管成像(CCTA)诊断为左前降支单支病变的冠状动脉粥样硬化性心脏病(冠心病)疑似患者的临床资料.患者入院1周内接受有创冠状动脉造影(ICA)及血流储备分数(FFR)检查,分析影像特征并计算CCTA...     

Doppler derived coronary flow reserve during dobutamine stress echocardiography further improves detection of myocardial ischemia.

BACKGROUND: The coronary flow velocity (CFV) has been used to estimate coronary flow reserve (CFR) during dobutamine stress echocardiography (DSE). However, the relationship of the CFR to myocardial wall thickening (WT) has not been investigated. OBJECTIVES: The aims of this study were: (1) to assess the feasibility of obtaining systolic and diastolic CFV and thus CFR during DSE and (2) to assess the relation between CFR and stress induced WT. METHODS: Distal left anterior descending CFV was recorded by transthoracic Doppler echocardiography during DSE. Systolic and diastolic velocities were measured at rest, low and peak dobutamine doses, simultaneously, WT of distal anteroseptal segment was assessed by 2D-guided M-mode. The CFV and CFR of patients with normal WT defined as thickening of >50% (group 1) at peak stress were compared to that of patients with abnormal WT (group 2). RESULTS: A total of 67 patients, 34 females and 33 males (mean age of 66.5+/-14.5 years) were studied. The feasibility of assessing the CFR was 97% from peak diastolic velocity, 91% from diastolic time velocity integral, 91% from peak systolic velocity, and 90% from systolic time velocity integral. Contrast agent was used in 6 patients (7%) to obtain the CFV. Twenty-five of 67 patients demonstrated abnormal wall thickening. The percentage of WT was 30.9+/-15.7% in group 2 compared to 80.8+/-24.3% in group 1 (p<0.0001). The 25 patients in group 2, who developed abnormal WT, demonstrated significantly lower CFR at low dose, as well as at peak dobutamine dose compared to patients in group 1 (1.55+/-0.5 vs. 2.03+/-0.6, p<0.008). CONCLUSION: CFV and CFR assessments are feasible during DSE with second harmonic imaging in most patients without use of contrast agent. CFR assessment during DSE correlates well with wall thickening and was able to detect ischemia early before development of wall motion abnormality.