Bernard De Bruyne

Validation of Fractional Flow Reserve in Animals

During maximum vasodilation, which corresponds with minimal myocardial resistance, distal coronary pressure divided by aortic pressure equals maximum myocardial blood flow divided by the normally expected value as it would be if no epicardial lesion were present1,2. The theoretical background of the concept of fractional flow reserve and its experimental validation have been provided in the preceding chapters. So far, however, pressure-derived fractional flow reserve has been validated in an open chest dog model against the ratio of epicardial hyperemic flow velocity in the presence of a stenosis to hyperemic flow velocity in the absence of a stenosis.

Practical Set-up of Coronary Pressure Measurement

The present chapter aims at providing the reader with the practical aspects of coronary pressure measurements in humans. The technical requirements, equipment, “tips and tricks” of the procedure itself, and methods to induce hyperemia are reviewed. Potential pitfalls to be aware of, are discussed in chapter 6.

Assessment of Collateral Blood Flow by Coronary Pressure Measurement

Although the importance and protective role of the collateral circulation of the heart have been recognized for decades, no methods have been available so far for quantitative assessment of collateral blood flow in conscious humans1–4.

Pitfalls in Coronary Pressure Measurement

As with every new technique, the cardiologist starting to perform coronary pressure measurements by wire technology will face some potential pitfalls which may lead to erroneous results or misinterpretation of data. Most of these pitfalls are easily recognized, a few are more tricky. There are some pitfalls specifically related to the equipment, to the guiding catheter used, to the use of the different hyperemic stimuli, and to specific physiologic or pathophysiologic conditions. Most of these pitfalls are easily avoided once the operator is aware of them.

FFR in Some Specific Conditions

An essential prerequisite for the calculation of FFR from aortic and coronary pressure is to obtain the measurements under conditions of maximum hyperemia. Only in this situation it can be assumed that the resistance of the vascular bed is minimal and therefore equal to the resistance in the same vascular bed but not depending on an epicardial stenosis. This condition has been demonstrated in animals (chapter 7) and in humans (chapter 8). Only when the resistance of the vascular bed depending on an epicardial stenosis equals the resistance of the same vascular bed but without stenosis, these resistances can be cancelled in the calculation of FFR2. It has been shown in animals and in humans, in the physiological range of aortic pressure, that the relation between myocardial flow and driving pressure is linear during maximum microvascular vasodilation3–4 This implies that, during maximum hyperemia, the ratio of two myocardial flows (which corresponds to the definition of FFR) equals the ratio of their respective driving pressures. The key point with respect to FFR is not the slope but the linearity of the pressure-flow relation under conditions of maximum vasodilation. When maximum hyperemia is not achieved the relation between hyperemic flow and driving pressure is curvilinear, and thus, the ratio of these (‘non-hyperemic’) flows does not equal the ratio of their respective driving pressures.

Fractional Flow Reserve for Evaluation of Coronary Interventions

Are there any values of myocardial fractional flow reserve (FFR myo ) after a coronary intervention, indicating that the result of the procedure was excellent, moderate, or insufficient ?

Fractional Flow Reserve and Clinical Outcome

There is ample inferential evidence that patients with physiologically significant stenoses are at increased risk1. Patients with proven coronary artery disease and in whom signs of myocardial ischemia are observed at low workload have an adverse event rate which is four times higher than in those with similar stenoses but in whom ischemia can only be provoked during exercise2,3. This relationship between inducible ischemia and poor prognosis has led to the wide acceptance of treating functionally important stenoses even though their angiographic appearance is mild or moderate. The converse, not treating angiographically significant but functionally mild lesions, remains more controversial. The prevalence of angiographically significant lesions in an arbitrary population of 60-year-old asymptomatic males, is 20% and many of these lesions have probably no functional significance4. However, cardiologists are reluctant to leave untreated an angiographically significant stenosis, even when no objective signs of ischemia can be induced. This explains, at least in part, why a considerable number of angioplasties are performed without proof of reversible myocardial ischemia5. It is likely that a number of these angioplasties are based on an “oculo-stenotic” reflex and are possibly unnecessary.

Conclusions and Perspectives for the Future

The usefulness of coronary pressure measurement has been recognized by the pioneers of balloon angioplasty, as testified by the presence of a fluid-filled lumen in the first generation of balloon catheters1. Since these early days, the interest in measuring distal coronary pressure has fluctuated between enthusiasm for having a simple index to assess coronary hemodynamics and disillusion due to the inconsistency of the results2–6.

Fractional Flow Reserve to Distinguish Significant Stenosis: Use at Diagnostic Catherization

The ultimate goal of every diagnostic method should be to facilitate clinical decision-making and to enable evaluation of the results of therapeutic interventions. This is especially true with respect to physiologic investigations in the catheterization laboratory. A number of studies establishing the value of coronary pressure measurement and FFR to distinguish between functionally significant and non-significant stenoses, is presented in this chapter.

Fractional Flow Reserve to Assess Intermediate Stenosis

As outlined in the previous chapters, myocardial fractional flow reserve (FFR myo ) is a lesion-specific index of the functional severity of a coronary stenosis, calculated from pressure measurements during coronary arteriography1–8. It has been shown in chapter 11 that a value of 0.75 distinguishes lesions, associated with reversible ischemia or not, with minimal overlap. In this chapter the usefulness of fractional flow reserve is investigated for clinical decision-making in patients with intermediate coronary stenosis, and compared to an ischemic standard composed by all presently used non-invasive tests: exercise testing, thallium scintigraphy, and dobutamine stress-echocardiography.