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In nuclear perfusion imaging of the myocardium, a false-negative test result in patients with balanced three-vessel disease is a well-known pitfall. This paper describes a patient with typical chest pain and a negative myocardial perfusion scintigram. At coronary angiography, intermediate stenoses in the left anterior descending (LAD), left circumflex (LCX), and right coronary (RCA) arteries were present. Fractional flow reserve, measured by coronary pressure measurement, was 0.54, 0.56, and 0.66 respectively for the LAD, LCX, and RCA, unequivocally demonstrating the presence of balanced three-vessel disease. The patient underwent successful bypass surgery and remained event-free thereafter.

In the decision-making process of revascularization of coronary artery stenoses by percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), the presence and extent of reversible ischemia associated with such particular stenoses is of paramount importance ([1–3][1

OBJECTIVE: Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. METHODS: Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). RESULTS: We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC) vs. 9633 (3580-21565) AUC, P

OBJECTIVE—To investigate the value of coronary pressure derived fractional flow reserve (FFR) measurements in supporting decisions about medical or surgical treatment in patients with angiographically equivocal left main coronary artery stenosis. DESIGN—A two centre prospective single cohort follow up study. INTERVENTIONS—FFR of the left main coronary artery was determined in 54 consecutive patients with angiographically equivocal left main coronary artery disease. If FFR was ⩾ 0.75, medical treatment was chosen; if FFR was

Background Fractional flow reserve (FFR) and coronary flow reserve (CFR) are indices of coronary stenosis severity that provide the clinician with complementary information on the contribution of epicardial arteries and microcirculation to total resistance to myocardial blood flow. At present, FFR and CFR can only be obtained by 2 separate guidewires. The present study tested the validity of the thermodilution principle in assessing CFR with one pressure-temperature sensor-tipped guidewire. Methods and Results In an in vitro model, absolute flow was compared with the inverse mean transit time (1/T mn ) of a thermodilution curve obtained after a bolus injection of 3 mL of saline at room temperature. A very close correlation ( r >0.95) was found between absolute flow and 1/T mn when the sensor was placed ≥6 cm from the injection site. In 6 chronically instrumented dogs (60 stenoses; FFR from 0.19 to 0.98), a significant linear relation was found between flow velocity and 1/T mn . A significant correlation was found between CFR Doppler , which was calculated from the ratio of hyperemic to resting flow velocities, and CFR thermo , which was calculated from the ratio of resting to hyperemic T mn ( r =0.76; SEE=0.24; P Conclusion The present findings demonstrate the validity of the thermodilution principle to assess CFR. Because the pressure-temperature sensor was mounted in a commercially available angioplasty guidewire, this technique permits simultaneous measurements of CFR and FFR.

Background —Coronary stenting improves outcomes compared with balloon angioplasty, but it is costly and may have other disadvantages. Limiting stent use to patients with a suboptimal result after angioplasty (provisional angioplasty) may be as effective and less expensive. Methods and Results —To analyze the cost-effectiveness of provisional angioplasty, patients scheduled for single-vessel angioplasty were first randomized to receive primary stenting (97 patients) or balloon angioplasty guided by Doppler flow velocity and angiography (523 patients). Patients in the latter group were further randomized after optimization to either additional stenting or termination of the procedure to further investigate what is “optimal.” An optimal result was defined as a flow reserve >2.5 and a diameter stenosis P =0.014). Results after the second randomization showed that stenting was also more effective after optimal balloon angioplasty (1-year event free survival, 93.5% versus 84.1%; P =0.066). Conclusions —After 1 year of follow-up, provisional angioplasty was more expensive and without clinical benefit. The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty.

Background. To investigate the functional capacity of the right gastroepiploic artery graft (GEA) and its ability to adapt to provide adequate flow at peak myocardial demand, we investigated the feasibility of determining coronary flow reserve (CFR) provided by this vessel using transabdominal color Doppler echocardiography and the correlation between this noninvasive determination of flow reserve and nuclear stress scintigraphy. Methods. In 40 selected patients, who underwent complete arterial myocardial revascularization using the GEA and the internal thoracic arteries (ITAs), CFR of the GEA was measured at maximum coronary hyperemia induced by intravenous adenosine infusion, 7 months (range 3 to 20) after surgery. In the same period, in 31 of this group of patients, exercise thallium scintigraphy was performed. Results. We succeeded in measuring CFR in 37 of 40 patients with values ranging from 1.1 to 3.6 with an average of 2.1 ± 0.7. During adenosine infusion, mean velocity in the GEA significantly increased from 48 ± 20 to 89 ± 41 cm/sec (p ≤ 0.001), mean arterial blood pressure significantly decreased from 96 ± 11 to 87 ± 11 mm Hg (p ≤ 0.001), and heart rate significantly increased from 74 ± 11 to 87 ± 15 beats/min (p ≤ 0.001). In 8 of these 37 patients, the nuclear exercise test was positive (compatible with reversible ischemia in the distribution area of the GEA). Average CFR in these 8 patients with positive nuclear stress test was 1.46 ± 0.28 versus 2.27 ± 0.70 in those patients with a negative test (p ≤ 0.001). Conclusions. Noninvasive determination of CFR of GEAs is feasible, using transabdominal Doppler echocardiography. The present study shows that coronary vasodilator reserve and autoregulation is maintained in myocardium supplied by the GEA and that the CFR has a significant correlation with the results of noninvasive nuclear exercise testing. Therefore, noninvasive determination of CFR by transabdominal Doppler echocardiography might be a valuable contribution to functional assessment of GEAs.

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.

Background —When several stenoses are present within 1 coronary artery, the hemodynamic significance of each stenosis is influenced by the presence of the other(s), and the calculation of coronary and fractional flow reserve (CFR and FFR) for each individual stenosis is confounded. Recently, we developed and experimentally validated a method to determine the true FFR of each stenosis as it would be after the removal of the other stenosis; the true FFR can be reliably predicted by coronary pressures measured before treatment at specific locations within the coronary artery using equations accounting for stenosis interaction. The aim of the present study was to test the validity of these equations in humans. Methods and Results —In this study of 32 patients with 2 serial stenoses in 1 coronary artery, relevant pressures were measured before the intervention, after the treatment of 1 stenosis, and after the treatment of both stenoses. The true FFR of each stenosis (FFR true ) was directly measured after the elimination of the other stenosis and compared with the value predicted (FFR pred ) from the initial pressure measurements before treatment. Although the hyperemic gradient across 1 stenosis increased significantly (from 10±7 to 19±11 mm Hg after treatment of the other stenosis), FFR pred was close to FFR true in all patients (0.78±0.12 versus 0.78±0.11 mm Hg; r =0.92; Δ%=4±0%). Without accounting for stenosis interaction, the value of FFR for each stenosis would have been significantly overestimated (0.85±0.08; P Conclusions —Coronary pressure measurements made by a pressure wire at maximum hyperemia provide a simple, practical method for assessing the individual hemodynamic significance of multiple stenoses within the same artery.

Recently, the interest in coronary pressure measurements has been revived thanks to technical innovations (the development of pressure-measuring angioplasty guidewire) and theoretical progress (the concept of pressure derived fractional flow reserve). Fractional flow reserve (FFR) is the ratio of maximal flow in the myocardial region depending on a stenosis to maximal flow in that same region if the stenosis were absent. With the development of pressure guidewires, fractional flow reserve can be calculated rapidly and safely in the diagnostic and interventional setting. It has been shown that pressure derived FFR can be used as a surrogate for a stress test for on-line clinical decision making in the catheterization laboratory. Values 0.75 exclude objective signs of ischemia during exercise. The accuracy of FFR for that purpose is approximately 95% and higher than that of any single noninvasive test taken alone. Of note, it has been shown that prognosis is favorable in patients in whom a planned angioplasty was deferred on the basis of a myocardial fractional flow reserve > 0.75. After regular balloon angioplasty, the combination of a good angiographic result and a FFR > 0.90 is associated with an event rate during a 2-year follow-up, which is similar to that after stenting. After stent implantation, FFR should normalize. A FFR < 0.94 after stent implantation appears to be as accurate as intravascular ultrasound (IVUS) to detect stent malposition. Thus, pressure derived FFR is a well-validated index of stenosis severity that has evolved from a physiological index to a clinical tool.

Background —Although intravascular ultrasound (IVUS) is the present standard for the evaluation of optimum stent deployment, this technique is expensive and not routinely feasible in most catheterization laboratories. Coronary pressure–derived myocardial fractional flow reserve (FFR myo ) is an easy, cheap, and rapidly obtainable index that is specific for the conductance of the epicardial coronary artery. In this study, we investigated the usefulness of coronary pressure measurement to predict optimum and suboptimum stent deployment. Methods and Results —In 30 patients, a Wiktor-i stent was implanted at different inflation pressures, starting at 6 atm and increasing step by step to 8, 10, 12, and 14 atm, if necessary. After every step, stent deployment was evaluated by quantitative coronary angiography (QCA), IVUS, and coronary pressure measurement. If any of the 3 techniques did not yield an optimum result, the next inflation was performed, and all 3 investigational modalities were repeated until optimum stent deployment was present by all of them or until the treating physician decided to accept the result. Optimum deployment according to QCA was finally achieved in 24 patients, according to IVUS in 17 patients, and also according to coronary pressure measurement in 17 patients. During the step-up, a total of 81 paired IVUS and coronary pressure measurements were performed, of which 91% yielded concordant results (ie, either an optimum or a suboptimum expansion of the stent by both techniques, P myo (48% and 46%, respectively). Conclusions —In this study, using a coil stent, both IVUS and coronary pressure measurement were of similar value with respect to the assessment of optimum stent deployment. Therefore, coronary pressure measurement can be used as a cheap and rapid alternative to IVUS for that purpose.

Background. In the selection of patients eligible for minimally invasive coronary artery bypass grafting (MICABG), knowledge about the pathophysiologic significance of individual coronary stenoses is important. Only if the lesion amenable to MICABG can be identified as the culprit lesion, and other lesions can be demonstrated not to be responsible for reversible ischemia, will MICABG be an appropriate procedure. Methods. By simultaneous measurement of mean aortic pressure and transstenotic coronary pressure, a pathophysiologic index can be obtained that specifically indicates the influence of an epicardial coronary stenosis on maximum achievable blood flow of the supplied myocardial territory. This index is called myocardial fractional flow reserve (FFR myo ). Results. Myocardial fractional flow reserve is a reliable, lesion-specific index for determining whether a particular stenosis is responsible for reversible myocardial ischemia. If FFR myo is less than 0.75, revascularization is indicated, whereas if FFR myo is greater than 0.75, revascularization usually is not warranted. Moreover, in contrast to classic coronary flow or flow velocity reserve, FFR myo is independent of changes in heart rate, blood pressure, and contractility, and also accounts for the contribution of collaterals. Conclusions. Pressure-derived FFR myo is an accurate pathophysiologic index for reliable identification of functionally significant epicardial lesions and can be obtained easily and quickly during routine cardiac catheterization. Therefore, FFR myo facilitates clinical decision-making with respect to the appropriateness of MICABG.

Objective: Atherosclerosis is associated with increased levels of plasma cytokines and expression of Toll-like receptors (TLRs). Yet, little is known about the potential use of TLR ligand induced cytokine release as a biomarker of coronary artery disease (CAD). In this study, we investigated whether TLR ligand induced cytokine release is associated with atherosclerotic disease severity and its predictive value for future cardiovascular events. Methods: Blood samples were obtained from 260 patients with stable angina and 15 healthy controls. Cytokine levels of TNFα, IL-8 and IL-6 were measured after 2h of whole blood stimulation with 10ng/ml lipopolysaccharide (LPS, TLR4 ligand) and P3C 500ng/ml (TLR2 ligand). In a subgroup, dose-response curves were created using additional LPS concentrations. Results: LPS induced whole blood release of TNFα and IL-6, but not IL-8, was significantly higher in patients compared to healthy controls. Among CAD patients, TLR responses did hardly differ when associated with the presence of traditional risk factors and atherosclerotic disease severity (number of diseased vessels and coronary stenosis degree). Patients with secondary events during follow-up showed a trend towards an increased TLR response. Furthermore, positive associations were found between CRP levels and TLR-induced TNFα (CRP2: 2364pg/ml) and IL-6 production (CRP2: 2250pg/ml). Conclusion: In conclusion, TLR-induced whole blood cytokine release in patients with stable angina indicates the presence of coronary atherosclerosis but does not reflect its severity.

We thank our colleagues Karabay et al for their interest and comments regarding our recent article entitled “Fractional Flow Reserve Assessment of Left Main Stenosis in the Presence of Downstream Coronary Stenoses.”1 They raise an important point about branch steal and how it may affect the pressure gradient in the presence of serial coronary stenoses. A recent in vitro study by our group demonstrated that the flow–pressure–resistance relationship in the setting of left main and downstream stenosis can be represented using a model of resistances.2 In the setting of a left main stenosis, let us consider the ostium of the left main artery as the inlet, with the …

Objectives This study sought to examine the clinical performance of and theoretical basis for the instantaneous wave-free ratio (iFR) approximation to the fractional flow reserve (FFR). Background Recent work has proposed iFR as a vasodilation-free alternative to FFR for making mechanical revascularization decisions. Its fundamental basis is the assumption that diastolic resting myocardial resistance equals mean hyperemic resistance. Methods Pressure-only and combined pressure-flow clinical data from several centers were studied both empirically and by using pressure-flow physiology. A Monte Carlo simulation was performed by repeatedly selecting random parameters as if drawing from a cohort of hypothetical patients, using the reported ranges of these physiologic variables. Results We aggregated observations of 1,129 patients, including 120 with combined pressure-flow data. Separately, we performed 1,000 Monte Carlo simulations. Clinical data showed that iFR was +0.09 higher than FFR on average, with +/- 0.17 limits of agreement. Diastolic resting resistance was 2.5 +/- 1.0 times higher than mean hyperemic resistance in patients. Without invoking wave mechanics, classic pressure-flow physiology explained clinical observations well, with a coefficient of determination of >0.9. Nearly identical scatter of iFR versus FFR was seen between simulation and patient observations, thereby supporting our model. Conclusions iFR provides both a biased estimate of FFR, on average, and an uncertain estimate of FFR in individual cases. Diastolic resting myocardial resistance does not equal mean hyperemic resistance, thereby contravening the most basic condition on which iFR depends. Fundamental relationships of coronary pressure and flow explain the iFR approximation without invoking wave mechanics. (J Am Coll Cardiol 2013;61:1428-35) (C) 2013 by the American College of Cardiology Foundation

UNLABELLED Intracoronary stents were implanted in 15 patients after unsuccessful PTCA in the setting of acute myocardial infarction (AMI). The stented vessel was the left anterior descending (LAD) in 11 patients, the right coronary artery (RCA) in 3 patients, and a venous bypass graft to the LAD in a single patient. A total of 16 stents were implanted (15 Palmaz Schatz, Johnson and Johnson; and 1 Wiktor, Medtronic). FOLLOW-UP 1 patient died 10 days after stent implantation as a result of renal failure and cardiogenic shock. Subacute thrombosis occurred in 2 patients, 5 and 15 days after stent implantation; both underwent successful emergency coronary artery bypass grafting (CABG). The remaining 12 patients were free from major ischemic events (death, AMI, and further revascularization) after a mean follow-up of 18.7 +/- 4.1 months. We conclude that the long-term results of intracoronary stenting in AMI after failed PTCA are favourable.

For calculation of fractional flow reserve (FFR), simultaneous registration of both aortic pressure (Pa) and transstenotic distal coronary pressure (Pd) is necessary at steady-state maximum coronary hyperemia. The aim of the present study was to compare the maximum transstenotic gradient (delta Pmax) and pressure-derived myocardial fractional flow reserve (FFRmyo), observed during intravenous adenosine infusion, to delta Pmax and FFRmyo induced by intracoronary papaverine, which is considered to be the gold standard for induction of coronary hyperemia, but acts too short for steady-state hyperemic pressure recordings and is associated with QT-prolongation. In 24 patients with coronary stenoses of various degrees, Pa and Pd were measured simultaneously by the diagnostic catheter and a high fidelity 0.018" fiberoptic pressure monitoring guide wire, respectively. Excellent steady-state phasic intracoronary pressure recordings were obtained in all patients within 1 min after start of intravenous adenosine infusion at a rate of 140 micrograms/kg/min, and compared to delta Pmax obtained 30 sec after intracoronary administration of papaverine (12 mg LCA, 10 mg RCA). Delta Pmax was 24 +/- 15 mmHg during adenosine infusion and 24 +/- 15 mmHg after papaverine administration. Myocardial fractional flow reserve, calculated from these pressure recordings, was 0.75 +/- 0.16 and 0.75 +/- 0.15, respectively, with an individual difference of 0.02 +/- 0.01 between both values (r = 0.99). No important side effects by intravenous infusion of adenosine were observed. Thus intravenous adenosine infusion at a rate of 140 micrograms/kg/min is an excellent and safe alternative for induction of steady-state maximum coronary hyperemia and therefore is an ideal vasodilator for determination of fractional flow reserve based upon pressure recordings.

Background Fractional flow reserve (FFR), defined as the ratio of maximum flow in the presence of a stenosis to normal maximum flow, is a lesion-specific index of stenosis severity that can be calculated by simultaneous measurement of mean arterial, distal coronary, and central venous pressure (P a , P d , and P v , respectively), during pharmacological vasodilation. The aims of this study were to define ranges of FFR values, whether associated with inducible ischemia or not, and to investigate FFR in normal coronary arteries. Methods and Results In 60 patients accepted for percutaneous transluminal coronary angioplasty (PTCA) of single-vessel disease, with a positive exercise test (ET) a was measured by the guiding catheter, P d by an 0.018-in fiber-optic pressure-monitoring wire, and P v by a multipurpose catheter. The ET was repeated after 5 to 7 days, and only if this second ET had reverted to normal was the pre-PTCA value of FFR definitely considered to be associated with inducible ischemia and the post-PTCA value not. Myocardial FFR (FFR myo ) increased from 0.53±0.15 before PTCA to 0.88±0.07 after PTCA. Coronary FFR increased from 0.38±0.19 to 0.83±0.12. In all patients, values of FFR myo definitely associated with ischemia were ≤0.74, whereas all except two values not associated with inducible ischemia exceeded 0.74. Moreover, FFR myo in 18 coronary arteries in 5 normal patients equaled 0.98±0.03. Conclusions A value of FFR myo of 0.74 reliably discriminates coronary stenosis, whether associated with inducible ischemia or not. Therefore, FFR myo is a useful index to determine the functional significance of an epicardial coronary stenosis and may facilitate clinical decision making in patients with an equivocal coronary stenosis.

Intracoronary flow assessment has remained underutilized relative to pressure measurements partly due to less robust tools for its measurement. We propose a novel technique called pressure-bounded CFR (pb-CFR) and demonstrate its application to the randomized DEFER trial to examine the prognosis of

Objectives. The present study was designed to evaluate the applicability of a pressure-flow equation for quantitative calculation of recruitable collateral blood flow at coronary artery occlusion in conscious patients and to investigate the value of that index to predict future ischemic events. Background. Recent experimental studies have indicated that recruitable collateral blood flow at coronary artery occlusion can be expressed as a fraction of normal maximal myocardial blood flow by simultaneous recordings of mean arterial, coronary wedge and central venous pressures, respectively. This index is called the pressure-derived fractional collateral flow and is independent of hemodynamic loading conditions. Methods. In 120 patients undergoing elective coronary angioplasty, mean arterial, coronary wedge and central venous pressures were measured at balloon inflations of 2 min. All patients had a recent exercise electrocardiogram (ECG) with positive findings showing clearly distinguishable, reversible ECG abnormalities, enabling recognition of ischemia at balloon inflation. Fractional collateral blood flow at angioplasty was calculated by coronary wedge pressure minus central venous pressure divided by mean arterial pressure minus central venous pressure and correlated to the presence or absence of ischemia at balloon inflation. Ischemic events were monitored during a follow-up period of 6 to 22 months. Results. In 90 of the 120 patients, ischemia was present at balloon inflation, and in 82 of these patients, fractional collateral blood flow was ≤23%. By contrast, in 29 patients, no ischemia was present, and fractional collateral blood flow was >24% in all 29. During the follow-up period, 16 patients had an ischemic event. Fifteen of these 16 patients were in the group with insufficient collateral flow (p Conclusions. To our knowledge, this study presents the first method for quantitative assessment of recruitable collateral blood flow in humans in the catheterization laboratory. Sufficient and insufficient collateral circulation can be reliably distinguished by this method. Use of this method can also help to provide more insight into the extent and behavior of the collateral circulation for investigational purposes and may have potential clinical implications.

When selecting coronary stenoses for interventional treatment, assessment of reversible ischaemia is paramount from a symptomatic as well as prognostic point of view. Fractional flow reserve (FFR) is now considered the gold standard for invasive assessment of ischaemia. By measuring FFR in the catheterization laboratory, one can accurately identify which lesions should be stented resulting in improved patient outcome in most elective clinical and angiographic conditions. Recently, in the European Society of Cardiology guidelines on coronary revascularization, FFR was upgraded to an IA classification in multivessel percutanous coronary intervention. In this review paper, the rationale for routine measurement of FFR will be reviewed and studies supporting its integration into everyday practice will be highlighted.

BACKGROUND: Atherosclerosis is an inflammatory condition and increased blood levels of inflammatory biomarkers have been observed in acute coronary syndromes. In addition, high expression of inflammatory markers is associated with worse prognosis of coronary artery disease. The presence and extent of inducible ischemia in patients with stable angina has previously been shown to have strong prognostic value. We hypothesized that evidence of inducible myocardial ischemia by local lesions, as measured by fractional flow reserve (FFR), is associated with increased levels of blood based inflammatory biomarkers.METHODS: Whole blood samples of 89 patients with stable angina pectoris and 16 healthy controls were analyzed. The patients with stable angina pectoris underwent coronary angiography and FFR of all coronary lesions. We analyzed plasma levels of cytokines IL-6, IL-8 and TNF-α and membrane expression of Toll-like receptor 2 and 4, CD11b, CD62L and CD14 on monocytes and granulocytes as markers of inflammation. Furthermore, we quantified the severity of hemodynamically significant coronary artery disease by calculating Functional Syntax Score (FSS), an extension of the Syntax Score.RESULTS: For the majority of biomarkers, we observed lower levels in the healthy control group compared with patients with stable angina who underwent coronary catheterization. We found no difference for any of the selected biomarkers between patients with a positive FFR (≤ 0.75) and negative FFR (>0.80). We observed no relationship between the investigated biomarkers and FSS.CONCLUSION: The presence of local atherosclerotic lesions that result in inducible myocardial ischemia as measured by FFR in patients with stable coronary artery disease is not associated with increased plasma levels of IL-6, IL-8 and TNF-α or increased expression of TLR2 and TLR4, CD11b, CD62L and CD14 on circulating leukocytes.

The potential benefit of revascularization depends on the presence and extent of myocardial ischemia. Performing percutaneous coronary intervention (PCI) on ischemia-inducing coronary stenoses improves both symptoms and outcome, while performing PCI on non-ischemia-inducing stenoses has no benefit and is potentially harmful. Noninvasive testing and the coronary angiogram have limited ability to distinguish specific ischemic territories and responsible stenoses, especially in multivessel coronary disease. To overcome these shortcomings, fractional flow reserve (FFR) has been developed as a stenosis-specific index to determine whether a coronary stenosis has ischemic potential. FFR-guided PCI improves both symptoms and outcome. As such, knowledge of coronary physiology and FFR has become imperative in daily coronary decision making.

Fractional flow reserve (FFR) is an index of coronary stenosis severity and has prognostic importance. iFR has been proposed as a new index which is independent of hyperemia (Sen et al J Am Coll Cardiol 2012). We aimed to compare iFR with FFR in unselected consecutive patients referred for PCI.

We developed a U-shaped diagnostic and guiding catheter for left coronary angiography and angioplasty. Angiography with a 6 French (F) diagnostic U-shaped catheter was attempted in 101 patients (pts). Primary use in 82 pts; all successful. Secondary use after failure of 6 F left Judkins diagnostic catheters to intubate the left main coronary artery in 19 pts; 17 successful. An 8 F U-shaped guiding catheter was used for percutaneous transluminal coronary angioplasty (PTCA) of left coronary artery branches in 102 pts [left anterior descending (LAD), 48 pts; circumflex (CX), 54 pts]. Stable cannulation of the left coronary artery was achieved in 96 pts (94%), but PTCA was successful in 90 pts (88%). Primary use in 70 pts (LAD, 27 pts; CX, 43 pts). PTCA was successful in 60 pts. Secondary use after failure of left Judkins and Amplatz guiding catheters in 32 pts (LAD, 21 pts; CX, 11 pts). PTCA was successful in 30 pts. No complications were seen. In conclusion, U-shaped diagnostic and guiding catheters increased the success rate of (1) left coronary angiography after failure of left Judkins diagnostic catheters; and (2) PTCA of the left anterior descending and circumflex arteries after failure of left Judkins and Amplatz guiding catheters © 1993 Wlley-Liss, Inc

Objectives. The present study was designed to investigate 1) the feasibility and accuracy of coronary pressure measurements with a novel 0.015-in. (0.038 cm) fluid-filled guide wire, and 2) the effect of the guide wire itself on stenosis hemodynamics.Background. To assess the functional results of coronary angioplasty, measurements of the transstenotic pressure gradient have been advocated. However, this is no longer routinely measured because it is not reliable when determined with the angioplasty catheter.Methods. A fluid-filled 0.015-in. guide wire to be connected to a conventional pressure transducer was developed. Five wires were tested for their frequency response characteristics and for their accuracy in measuring hydrostatic pressure. In an in vitro model of stenosis (reference diameter 4 mm), the pressure gradient was determined at incremental flow levels for varying stenosis severity with and without a 0.015-in. guide wire through the narrowing. In 37 patients, the transstenotic pressure gradient was measured before and after angioplasty and compared with obstruction area and percent area stenosis as determined by quantitative coronary angiography.Results. The correlation between the actual pressure and the pressure recorded by the guide wire was excellent (r = 0.98) despite a slight underestimation (−3 ± 5%). Phasic pressure recordings were precluded by a long time constant of 16 ± 4 s. The presence of the guide wire produced a significant overestimation (>20%) of the pressure decrease only in cases of tight stenosis (>90% area reduction). Furthermore, a theoretic model based on the fluid dynamic equation predicted that this overestimation was inversely proportional to the reference diameter of the vessel, yet was only slightly influenced by the flow. The lesion was crossed in all but one (97%) and pressure gradient was recorded throughout the study in 34 (94%) of 36 patients. The mean pressure gradient decreased from 30 ± 19 before to 3 ± 5 mm Hg after angioplasty (p < 0.01). A curvilinear relation was found between the pressure gradient and both percent area stenosis (r2= 0.67) and obstruction area (r2= 0.72). A sharp increase in pressure gradient was noted once the stenosis exceeded 75% area reduction.Conclusions. Mean transstenotic pressure gradients can be easily and reliably recorded with a 0.015-in. fluid-filled guide wire. This ability should facilitate the functional assessment of coronary stenoses of intermediate severity and of immediate postangioplasty results.

BACKGROUND Severity of coronary artery stenosis has been defined in terms of geometric dimensions, pressure gradient-flow relations, resistance to flow and coronary flow reserve, or maximum flow capacity after maximum arteriolar vasodilation. A direct relation between coronary pressure and flow, however, may only be presumed if the resistances in the coronary circulation are constant (and minimal) as theoretically is the case during maximum arteriolar vasodilation. In that case, pressure measurements theoretically can be used to predict maximum flow and assess functional stenosis severity. METHODS AND RESULTS A theoretical model was developed for the different components of the coronary circulation, and a set of equations was derived by which the relative maximum flow or fractional flow reserve in both the stenotic epicardial artery and the myocardial vascular bed and the proportional contribution of coronary arterial and collateral flow to myocardial blood flow are calculated from measurements of arterial, distal coronary, and central venous pressures during maximum arteriolar vasodilation. To test this model, five dogs were acutely instrumented with an epicardial, coronary Doppler flow velocity transducer. Distal coronary pressures were measured by an ultrathin pressure-monitoring guide wire (0.015 in.) with minimal influence on transstenotic pressure gradient. Fractional flow reserve was calculated from the pressure measurements and compared with relative maximum coronary artery flow measured directly by the Doppler flowmeter at three different levels of arterial pressure for each of 12 different severities of stenosis at each pressure level. Relative maximum blood flow through the stenotic artery (Qs) measured directly by the Doppler flowmeter showed an excellent correlation with the pressure-derived values of Qs (r = 0.98 +/- 0.01, intercept = 0.02 +/- 0.03, slope = 0.98 +/- 0.04), of the relative maximum myocardial flow (r = 0.98 +/- 0.02, intercept = 0.26 +/- 0.07, slope = 0.73 +/- 0.08), and of the collateral blood flow (r = 0.96 +/- 0.04, intercept = 0.24 +/- 0.07, slope = -0.24 +/- 0.06). Moreover, the theoretically predicted constant relation between mean arterial pressure and coronary wedge pressure, both corrected for venous pressure, was confirmed experimentally (r = 0.97 +/- 0.03, intercept = 9.5 +/- 13.3, slope = 4.4 +/- 1.2). CONCLUSIONS These results provide the experimental basis for determining relative maximum flow or fractional flow reserve of both the epicardial coronary artery and the myocardium, including collateral flow, from pressure measurements during maximum arteriolar vasodilation. With a suitable guide wire for reliably measuring distal coronary pressure clinically, this method may have potential applications during percutaneous transluminal coronary angioplasty for assessing changes in the functional severity of coronary artery stenoses and for estimating collateral flow achievable during occlusion of the coronary artery.

Petraco et al. [(1)][1] raise a universal issue that affects all clinical tests. Every binary cutoff produces cases just on either side of the threshold for whom a repeat measurement might alter the decision, no matter how accurate the test or how small its variability. By analogy to a Gaussian

The influence of atherosclerosis and its risk factors on coronary microvascular function remain unclear as current methods of assessing microvascular function do not specifically test the microcirculation in isolation. We examined the influence of epicardial vessel atherosclerosis on coronary microvascular function using the index of myocardial resistance (IMR).IMR (a measure of microvascular function) and fractional flow reserve (FFR, a measure of the epicardial compartment) were measured in 143 coronary arteries (116 patients). Fifteen patients (22 arteries, mean age 48+/-16 years) had no clinical evidence of atherosclerosis (control group). One hundred and one patients (121 arteries, mean age 63+/-11 years) had established atherosclerosis and multiple cardiovascular risk factors (atheroma group). Mean IMR in the control group (19+/-5, range 8-28) was significantly lower than in the atheroma group (25+/-13, range 6-75) (P0.01). However, there was large overlap between IMR in both groups, with 69% of IMR values in patients with atheroma being within the control range. Mean FFR was also higher in the control group (0.96+/-0.02, range 0.93-1.00) than in the atheroma group (0.85+/-0.14, range 0.19-1.00) (P0.01). There was no correlation between IMR and FFR (r=0.09; P=0.24), even when results in the control (r=0.02; P=0.92) and atheroma (r=0.15; P=0.10) groups were analysed in isolation. Using stepwise multiple regression analysis presence/absence of atheroma (ss=0.42; P=0.02) was the only independent determinant of IMR.Mean IMR is higher in patients with epicardial atherosclerosis. However, there is a large overlap between IMR in patients with and without epicardial atherosclerosis.

Objectives: We investigated the reliability of fractional flow reserve (FFR) of nonculprit coronary stenoses during percutaneous coronary intervention (PCI) in acute myocardial infarction. Background Assessing the hemodynamic severity of the nonculprit coronary artery stenoses at the acute phase of a myocardial infarction could improve risk stratification and shorten the diagnostic work-up. Methods One hundred one patients undergoing PCI for an acute myocardial infarction (n = 75 with ST-segment elevation myocardial infarction [STEMI], and n = 26 with nonST-segment elevation myocardial infarction) were prospectively recruited. The FFR measurements in 112 nonculprit stenoses were obtained immediately after PCI of the culprit stenosis and were repeated 35 ± 4 days later. In addition, left ventricular ejection fraction, quantitative coronary angiographic measurements of the nonculprit stenoses, Thrombolysis In Myocardial Infarction (TIMI) flow, corrected TIMI frame count (cTFC), and the index of microcirculatory resistance (n = 14) of the nonculprit vessels were assessed in the acute phase and at control angiogram. Results The FFR value of the nonculprit stenoses did not change between the acute and follow-up (0.77 ± 0.13 vs. 0.77 ± 0.13, respectively, p = NS). In only 2 patients, the FFR value was higher than 0.8 at the acute phase and lower than 0.75 at follow-up. The TIMI flow, cTFC, percentage diameter stenosis, minimum lumen diameter, and index of microcirculatory resistance did not change. Left ventricular ejection fraction increased significantly in patients with STEMI (from 54 ± 13% to 57 ± 13%, p = 0.03). Conclusions During the acute phase of acute coronary syndromes, the severity of nonculprit coronary artery stenoses can reliably be assessed by FFR. This allows a decision about the need for additional revascularization and might contribute to a better risk stratification. © 2010 American College of Cardiology Foundation.

Fractional Flow Reserve (FFR), calculated by coronary pressure measurement, is the invasive gold standard to assess the hemodynamic significance of a coronary stenosis. FFR reliably indicates whether a stenosis is responsible for inducible ischemia and if percutaneous coronary intervention is appropriate. False positive or negative FFR is rare. Occasionally, however, a clinical or angiographic condition is encountered in which in first instance the FFR measurement contradicts the intuitive feeling of the interventionalist. Further examination in such cases, however, often reveals a clear physiologic explanation and in this manner FFR "lifts the veil". Two such patients are presented in this case report and the reasons for apparent or actual false positive or negative FFR are discussed.

Aims: A ratio of distal renal pressure to aortic pressure (P d/Pa) angio), minimal luminal diameter (MLD), Doppler-derived peak systolic velocity (PSV), end-diastolic velocity (EDV), and renal-to-aortic ratio (RAR) were obtained and compared with the Pd/Pa measured with a 0.014" pressure wire. Pd/Pa correlated with angiography- and CDUS-derived parameters. The best correlation was observed with EDV (R = -0.61). To identify stenosis associated with a P d/Pa < 0.90, the diagnostic accuracy of DS angio > 50%, MLD < 2 mm, PSV > 180 cm/s, EDV > 90 cm/s and RAR > 3.5 were, respectively, 60%, 77%, 45%, 77% and 79%, yet, with a high proportion of false positives (38%, 15%, 55%, 11% and 15%, respectively) indicating an overestimation of the severity of the RAS by both QRA and CDUS. New cut-off values for QRA- and CDUS-derived indices were proposed. Conclusion: Generally accepted QRA and CDUS-derived indices of RAS severity overestimate the actual severity of RAS. This 'overdiagnosis' is likely the main cause of the disappointing results of renal angioplasty for renovascular hypertension.

Background: The angiography has been used as a reference standard to define coronary artery disease (CAD), although its limitations are well-known. The significance of the myocardial fractional flow reserve (FFR) in the assessment of CAD is well established. Objective:The aim of this study was to evaluate the accuracy of angiography when defining ischemic lesions and its correlation with FFR. Methods:Two hundred and fifty consecutive patients (471 arteries) were included in this study. All stenoses ≥ 50% at the angiography visual estimate (AVE) were assessed by FFR measurements. When FFR was < 0.75, stenting was performed; when FFR was ≥ 0.75, no interventional treatment was carried out. Offline quantitative coronary angiography (QCA) was performed in all stenoses, which were divided in intermediate (< 70% - 327) and severe (125). The correlation coefficients between the diameter of the stenosis (%DS) and FFR and the accuracy of VA of the angiography when assessing ischemia were determined. Results: FFR could be obtained in 452 lesions (96%). Mean %DS and FFR were 56 ± 8% and 0.74 and 76 ± 6% and 0.48 for moderate and severe stenoses, respectively. Concordance between QCA and FFR was poor, especially in intermediate stenoses (Spearman's rho = - 0.33, p

In an effort to better predict the risk of rupture of an abdominal aortic aneurysm (AAA), methods have been developed that comprise more than diameter information alone. Wall stress calculations demonstrated superior results compared to the diameter criterion [1]. Accurate wall stress calculations require patient specific geometry, load, and wall properties of the aneurysm [2]. Usually, values for mechanical properties obtained from in-vitro tensile tests of excised aneurysmal wall material are used for wall stress calculations [3]. For obvious reasons such experiments to obtain vessel properties are impossible to perform in patient specific cases for risk assessment.Copyright © 2008 by ASME

The limitation of coronary angiography to assess the functional significance of coronary stenosis as well as coronary restenosis has been recognized for years (1,2). It is well known that the angiographic assessment of an epicardial lesion correlates poorly with its physiological relevance (3,4). Coronary angiography with its inherent limitations may not reliably predict whether a stenosis produces ischemia (5). In addition, the determination of the severity of stenoses varies significantly among observers. In one study, experienced operators disagreed 30% of the time when deciding on the number of coronary arteries with a 70% stenosis (6). Despite these limitations the decision for performing an intervention is often based on the angiographic appearance of a coronary lesion. It is known from many angiographic studies that revascularization rate increases after scheduled control angiography meaning that repeat intervention is more often based on morphological criteria, i. e., quantitative coronary angiography or solely “eye balling” than on physiological considerations (7). Furthermore, as restenosis, which means in most of the cases in-stent restenosis may occur as a diffuse, proliferative process, the assessment of the hemodynamic significance is even more complex by angiography alone.

OBJECTIVES: The purpose of this work was to establish the normal range of maximal renal hyperemic response in humans and to identify the ideal renal vasodilatory stimuli. BACKGROUND: Stenotic renovascular atherosclerosis is increasingly treated by percutaneous transluminal renal intervention but with an unpredictable outcome. This may be due to hemodynamically non-significant stenosis or the presence of irreversible damage to the glomerular circulation. We propose that the renovascular hyperemic response may help identify appropriate patients. METHODS: In 28 normotensive patients, quantitative angiographic measurements of the renal artery were obtained, and renal artery pressure and flow velocity were continuously recorded after various hyperemic agents. RESULTS: In a first group of 11 patients, a significant increase in renal artery average peak velocity (APV) was observed after intrarenal (IR) bolus injection of 600 μg isosorbide dinitrate (41 ± 19%), 30 mg papaverine (50 ± 34%), 50 μg dopamine (94 ± 54%), 0.8 μg·kg-1 fenoldopam (80 ± 25%), and during IR infusion of 1 μg·kg-1·min-1 fenoldopam (86 ± 28%). A second group of 17 patients received intravenous infusion of dopamine (3, 5, 10, 20, 30, and 40 μg·kg -1·min-1). The 3 and 5 μg·kg -1·min-1 of dopamine modestly reduced renal resistance index (RI) (-13 ± 15% and -25 ± 20%, respectively). At higher dosages, no further decline in RI was observed. No significant change in vessel diameter was observed before and after the administration of the pharmacological stimuli suggesting that changes in APV corresponded with changes in absolute renal blood flow. CONCLUSIONS: The normal renal flow reserve averages approximately 2 in humans with normal renal function. An IR bolus injection of 50 μg·kg-1 of dopamine is the most convenient means to elicit maximal renal hyperemia.

OBJECTIVES: We sought to investigate the effect of intrinsic conduction over the right bundle on the maximum rate of left ventricular pressure rise (LVdP/dtmax) during left ventricular (LV) pacing compared to biventricular (BiV) pacing. BACKGROUND: Simultaneous BiV pacing and LV pacing both improve LV function in patients with heart failure and LV asynchrony. We studied the hemodynamic effect of intrinsic conduction leading to ventricular fusion during LV pacing. METHODS: In 34 patients with New York Heart Association functional class III or IV, sinus rhythm with normal atrioventricular (AV) conduction, left bundle branch block, QRS >130 ms, and optimal medical therapy, LVdP/dtmax was measured invasively during LV and simultaneous BiV pacing. The AV interval was varied in four steps starting (AV1) with an AV interval 40 ms shorter than the intrinsic PQ time and decreased with 25% for each step. RESULTS: At AV1, LVdP/dtmax was 996 ± 194 mm Hg/s for LV pacing and 960 ± 200 mm Hg/s for BiV pacing (p = 0.0009), with all patients showing ventricular fusion during LV pacing. At AV2, 21 patients had ventricular fusion with a LVdP/dtmax of 983 ± 213 mm Hg/s and 957 ± 202 mm Hg/s for LV and BiV pacing, respectively. In the remaining 13 patients without fusion these values were 919 ± 164 mm Hg/s and 957 ± 174 mm Hg/s, respectively. The difference between LV and BiV at AV2 is significantly higher when fusion is present (p = 0.01). CONCLUSIONS: The LVdP/dtmax is higher in LV than in BiV pacing provided that LV pacing is associated with ventricular fusion caused by intrinsic activation.

Background— Whether minimal microvascular resistance of the myocardium is affected by the presence of an epicardial stenosis is controversial. Recently, an index of microcirculatory resistance (IMR) was developed that is based on combined measurements of distal coronary pressure and thermodilution-derived mean transit time. In normal coronary arteries, IMR correlates well with true microvascular resistance. However, to be applicable in the case of an epicardial stenosis, IMR should account for collateral flow. We investigated the feasibility of determining IMR in humans and tested the hypothesis that microvascular resistance is independent of epicardial stenosis. Methods and Results— Thirty patients scheduled for percutaneous coronary intervention were studied. The stenosis was stented with a pressure guidewire, and coronary wedge pressure (P w ) was measured during balloon occlusion. After successful stenting, a short compliant balloon with a diameter 1.0 mm smaller than the stent was placed in the stented segment and inflated with increasing pressures, creating a 10%, 50%, and 75% area stenosis. At each of the 3 degrees of stenosis, fractional flow reserve (FFR) and IMR were measured at steady-state maximum hyperemia induced by intravenous adenosine. A total of 90 measurements were performed in 30 patients. When uncorrected for P w , an apparent increase in microvascular resistance was observed with increasing stenosis severity (IMR=24, 27, and 37 U for the 3 different degrees of stenosis; P w is appropriately accounted for, microvascular resistance did not change with stenosis severity (IMR=22, 23, and 23 U, respectively; P =0.28). Conclusions— Minimal microvascular resistance does not change with epicardial stenosis severity, and IMR is a specific index of microvascular resistance when collateral flow is properly taken into account.

In 1993, 1450 coronary interventions were performed in the Catharina Hospital in Eindhoven, the Netherlands. At that time, due to financial restraints, stents were not available. After two years of follow up, the reintervention rate in that population was 28%. In 1998, stents were available unrestrictedly in the same hospital and 1790 coronary interventions were performed. In that year, stents were implanted in 70% of the procedures and the reintervention rate after two years was 21%. In other words, comparing the pre-stent era with the stent era showed that the reintervention rate in the complete percutaneous coronary intervention (PCI) population in our hospital decreased from 28% to 21%. Thus, the reintervention rate in the stent era had decreased by 25% compared to the pre-stent era. While this decrease in the reintervention rate is not small, it is not that large either. It means that the re-intervention rate today is in the range of 20% if a completely unselected “true life” patient population is considered. And it is beyond doubt that the interventional community has eagerly waited for further developments to decrease this 20% reintervention rate. Recently, we have witnessed the dawn of what might be a new era—the era of drug eluting stents.1,2 It will be unrealistic to suppose that the restenosis rate of these new stents will be zero. But if they fulfil only half of their promise, this would be a great step forward and be of major importance for interventional cardiology. Let us suppose that the restenosis rate of these drug eluting stents will be very low indeed, somewhere in the range of 10% at 1–2 years, and that no major unexpected long term side effects will occur. What will be the consequences for the practice of interventional cardiology? Most likely, such a development will …

Maximal hyperaemia is paramount in the diagnosis of patients with coronary artery disease. However in these patients, enhanced α-adrenergic microvascular vasoconstriction may preclude adenosine to induce maximal hyperaemia. To assess the presence and the clinical relevance of residual microvascular resistance after administration of adenosine. Fractional flow reserve (FFR, calculated by coronary pressure measurements during adenosine-induced hyperaemia) was assessed in 85 patients with an intermediate coronary stenosis (mean diameter stenosis of 50 ± 1%) and normal left ventricular function which were divided into the following three groups: (a) 33 patients before and after IC bolus of phentolamine, an α 1-, α 2-adrenergic blocker; (b) 32 patients before and after IC bolus of urapidil, a selective α 1-adrenergic blocker; (c) 20 patients before and after IC bolus of saline. Since minimal luminal diameter remained unchanged before and after phentolamine (1.46 ± 0.06 vs. 1.47 ± 0.06 mm, ns), urapidil (1.46 ± 0.06 vs. 1.39 ± 0.08, ns), and saline (1.56 ± 0.08 vs. 1.55 ± 0.08, ns), changes in FFR reflects changes in microvascular resistance. Overall, phentolamine and urapidil induced a slight but significant decrease in FFR (phentolamine: 0.79 ± 0.02 vs. 0.77 ± 0.02, p < 0.05; urapidil: 0.78 ± 0.02 vs. 0.75 ± 0.02, p < 0.05). However, only 6 patients showed a change in FFR from ≥0.75 to

Time-density curves from regions of interest in digitized X-ray images of a coronary-artery/myocardium model were used to derive parameters representing flow and volume. The complete time-density curve was predicted from the observed time-limited, sampled time-density curve by least-squares methods, allowing accurate computation of mean transit time and relative vascular volume. In agreement with indicator-dilution theory, the experiments reveal that not the maximum density but rather the integral of the time-density curve should be used to assess vascular volume. >

Background— Inducing both maximal and steady-state coronary hyperemia is of clinical importance to take full advantage of fractional flow reserve measurements. The present study compares different dosages and routes of administration of adenosine 5′-triphosphate (ATP), adenosine, contrast medium, and papaverine regarding their potential to achieve both maximal and steady-state hyperemia. Methods and Results— In 21 patients with an isolated coronary stenosis, coronary vasodilation was induced successively by papaverine (20 mg intracoronary), adenosine (20 and 40 μg intracoronary), ATP (20 and 40 μg intracoronary), iohexol (6 mL intracoronary), adenosine or ATP through an antecubital vein (140 and 180 μg · kg − 1 · min − 1 ), or adenosine or ATP through a femoral vein (140 and 180 μg · kg − 1 · min − 1 ). Because vessel dimensions did not change, the ratio of distal coronary pressure (P d ) to aortic pressure (P a ) was used as an index of myocardial resistance. P d /P a was 0.77±0.21 at rest and decreased to 0.61±0.21 after papaverine. P d /P a decreased to a similar level with all other vasodilators, except with contrast medium (0.68±0.21; P − 1 · min − 1 . At doses >140 μg · kg − 1 · min − 1 , there was neither a further decrease in P d /P a ratio nor a further increase in coronary flow velocities. Conclusion— Provided sufficient dosages are used, ATP, adenosine, and papaverine (but not contrast medium) induce maximal hyperemia and are therefore suitable to assess fractional flow reserve. Only intracoronary papaverine and intravenous ATP or adenosine induce steady-state hyperemia enabling a pressure pullback maneuver that is useful in assessing diffuse coronary atherosclerosis.

We read the paper by Sen et al. ([1][1]) with great interest. We have a number of concerns regarding the proposed index, instantaneous wave-free ratio (iFR). First, the validity of iFR depends on the assumption that minimum resting myocardial resistance during diastole is equivalent to the mean

Background: In multivessel disease, it is controversial whether complete revascularization by bypass surgery (CABG) is superior to PTCA of the culprit lesions only. Fractional flow reserve (FFR), calculated from coronary pressure measurement, is a reliable index to identify whether a stenosis is culprit (i.e., functionally significant). Aim: To compare selective PTCA of culprit lesions only (FFR less than 0.75) to CABG of all stenoses. Methods: In 130 patients, referred for CABG, FFR was determined in 322 coronary arteries which were all considered for bypass grafting based on angiographic information only. If FFR was less than 0.75 in 3 or 2 stenoses including those located in the proximal left anterior descending coronary artery (LAD), CABG was performed on all vessels for which bypass grafting was considered to be necessary as judged angiographically by the surgeon and cardiologist who were blinded to the FFR results (CABG group). If only 1 or 2 lesions not including proximal LAD were culprit, PTCA of those lesions only was performed (PTCA group). Results: So far a 2 year follow-up has been completed in 75 patients assigned to CABG and 55 to PTCA. After 2 years, no differences were seen in adverse events (event-free survival 84.1% in the CABG group and 83.9% in the PTCA group) and a similar number of patients were free from angina (85% in the CABG group and 82% in the PTCA group). Conclusion: In multivessel disease, coronary pressure measurement is an excellent tool to identify the culprit lesion(s) by FFR < 0.75. In this way, patients with otherwise similar angiographic characteristics can be stratified into 2 groups, according to the functional extent of disease: patients with one or 2 culprit lesions excluding proximal LAD (PTCA group) and patients with 2 including LAD or more culprit lesions (CABG group). Within the group of patients with angiographically identified multivessel disease, PTCA of culprit lesion(s) only, as discriminated by an FFR of less than 0.75, yields a similar 2-year outcome as complete revascularization by bypass surgery.

Provisional or conditional stenting should be defined as the use of stents limited to those conditions and cases in which the operator, despite an aggressive balloon angioplasty technique with large balloons and high pressure, has been unable to obtain a result that ensures optimal chances of early and late patency. The paramount issue is how to discriminate the patients with optimal results after balloon angioplasty for whom additional stent implantation is unlikely to improve or may even worsen long-term outcome. The better results of elective stent implantation in the OPUS study suggest that visual assessment of the PTCA result is not sufficient to detect lesions with suboptimal lumen gain after PTCA. The addition of physiologic parameters (Doppler flow velocity measurements, fractional flow reserve) has improved the results of the provisional stent group, with the best outcome observed when complex lesions and multivessel treatment were included in these studies (FROST, DESTINI). Intravascular ultrasound, although more expensive and time-consuming, has the additional advantage to guide the dilatation strategy.

OBJECTIVES This study aimed to investigate the roles of intracoronary derived coronary flow velocity reserve (CFVR) and myocardial perfusion scintigraphy (single photon emission computed tomography, or SPECT) for management of an intermediate lesion in patient, with multivessel coronary artery disease. BACKGROUND Evaluation of the functional significance of intermediate coronary narrowings (40% to 70% diameter stenosis) is important for clinical decision making and risk stratification. METHODS In a prospective, multicenter study, SPECT was performed in 191 patients with stable angina and multivessel disease and scheduled for angioplasty (percutaneous transluminal coronary angioplasty or PTCA) of a severe coronary narrowing. Coronary flow velocity reserve was determined selectively distal to an intermediate lesion in another artery using a Doppler guidewire. Percutaneous transluminal coronary angioplasty of the intermediate lesion was deferred when SPECT was negative or CFVR greater than or equal to2.0. Patients were followed for one year to document major cardiac events (death, infarction, revascularization), related to the intermediate lesion. RESULTS Reversible perfusion defects were documented in the area of the intermediate lesion in 30 (16%) patients; CFVR was positive in 46 (24%) patients, Percutaneous transluminal coronary angioplasty of the intermediate lesion was deferred in 182 patients. During follow-up, 19 events occurred (3 myocardial infarctions, 16 revascularizations). Coronary flow velocity reserve was a more accurate predictor of cardiac events than was SPECT; relative risk: CFVR 3.9 (1.7 to 9.1), p