Hans Bonnier

Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses

BACKGROUND The clinical significance of coronary-artery stenoses of moderate severity can be difficult to determine. Myocardial fractional flow reserve (FFR) is a new index of the functional severity of coronary stenoses that is calculated from pressure measurements made during coronary arteriography. We compared this index with the results of noninvasive tests commonly used to detect myocardial ischemia, to determine the usefulness of the index. METHODS In 45 consecutive patients with moderate coronary stenosis and chest pain of uncertain origin, we performed bicycle exercise testing, thallium scintigraphy, stress echocardiography with dobutamine, and quantitative coronary arteriography and compared the results with measurements of FFR. RESULTS In all 21 patients with an FFR of less than 0.75, reversible myocardial ischemia was demonstrated unequivocally on at least one noninvasive test. After coronary angioplasty or bypass surgery was performed, all the positive test results reverted to normal. In contrast, 21 of the 24 patients with an FFR of 0.75 or higher tested negative for reversible myocardial ischemia on all the noninvasive tests. No revascularization procedures were performed in these patients, and none were required during 14 months of follow-up. The sensitivity of FFR in the identification of reversible ischemia was 88 percent, the specificity 100 percent, the positive predictive value 100 percent, the negative predictive value 88 percent, and the accuracy 93 percent. CONCLUSIONS In patients with coronary stenosis of moderate severity, FFR appears to be a useful index of the functional severity of the stenoses and the need for coronary revascularization.

Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease.

BACKGROUND The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. METHODS A total of 1205 patients were randomly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. RESULTS At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery (P<0.001 by the log-rank test). The costs for the initial procedure were

Fractional Flow Reserve A Useful Index to Evaluate the Influence of an Epicardial Coronary Stenosis on Myocardial Blood Flow

4,212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be

Quantification of recruitable coronary collateral blood flow in conscious humans and its potential to predict future ischemic events

2,973 per patient. CONCLUSION As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization.

Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery: Validation in humans

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 (Pa, Pd, and Pv, 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) < 24 hours before PTCA, FFR was determined during adenosine-induced hyperemia just before and 15 minutes after angioplasty. Pa was measured by the guiding catheter, Pd by an 0.018-in fiber-optic pressure-monitoring wire, and Pv, 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 (FFRmyo) 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 FFRmyo definitely associated with ischemia were < or = 0.74, whereas all except two values not associated with inducible ischemia exceeded 0.74. Moreover, FFRmyo in 18 coronary arteries in 5 normal patients equaled 0.98 +/- 0.03. CONCLUSIONS A value of FFRmyo of 0.74 reliably discriminates coronary stenosis, whether associated with inducible ischemia or not. Therefore, FFRmyo 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.

Long-Term Follow-Up After Deferral of Percutaneous Transluminal Coronary Angioplasty of Intermediate Stenosis on the Basis of Coronary Pressure Measurement

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 < or = 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 < 0.05). 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.

Fractional Flow Reserve

BackgroundWhen 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 ResultsIn 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 (FFRtrue) was directly measured after the elimination of the other stenosis and compared with the value predicted (FFRpred) 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), FFRpred was close to FFRtrue in all patients (0.78±0.12 versus 0.78±0.11 mm Hg;r =0.92; &Dgr;%=4±0%). Without accounting for stenosis interaction, the value of FFR for each stenosis would have been significantly overestimated (0.85±0.08;P <0.01). ConclusionsCoronary 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.

Comparison of Quantitative Coronary Angiography, Intravascular Ultrasound, and Coronary Pressure Measurement to Assess Optimum Stent Deployment

OBJECTIVES This study sought to determine the safety of deferral of percutaneous transluminal coronary angioplasty (PTCA) of angiographically intermediate but functionally nonsignificant stenosis, as assessed by coronary pressure measurement and myocardial fractional flow reserve (FFRmyo). BACKGROUND Decision making in patients with chest pain and intermediate coronary stenosis remains difficult. In these cases it is unclear whether the risk of an intervention and the potentially subsequent restenosis outweigh the future risk of an event if the lesion remains untreated. FFRmyo is a lesion-specific functional index of epicardial stenosis severity that accurately distinguishes stenoses associated with inducible ischemia. METHODS Retrospective analysis and follow-up was performed in 100 consecutive patients referred to our centers for PTCA of an intermediate stenosis but in whom the planned intervention was deferred on the basis of an FFRmyo > or = 0.75. RESULTS During a follow-up period of 18+/-13 months (mean +/- SD, range 3 to 42), two patients died of noncardiac causes. Ninety patients remained free of any coronary events, and their average Canadian Cardiovascular Society class decreased from 2.0+/-1.2 at baseline to 0.7+/-0.9 at follow-up (p < 0.0001). A coronary event occurred in eight patients and was target-vessel related in four. CONCLUSIONS In patients with chest pain referred for PTCA of an intermediate stenosis, deferral of the intervention on the basis of an FFRmyo > or = 0.75 is safe and is associated with a much lower clinical event rate than if the procedure had been performed as initially planned in these patients.

Early- and Long-Term Intravascular Ultrasound and Angiographic Findings After Bioabsorbable Magnesium Stent Implantation in Human Coronary Arteries

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.

Usefulness of Fractional Flow Reserve to Predict Clinical Outcome After Balloon Angioplasty

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 (FFRmyo) 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<0.00001). On the contrary, QCA showed a low concordance rate with IVUS and FFRmyo (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.