Response to Michiels et al and Sen et al Regarding Article, “Diagnostic Accuracy of Combined Intracoronary Pressure and Flow Velocity Information During Baseline Conditions: Adenosine-Free Assessment of Functional Coronary Lesion Severity”

Abstract

We would like to thank the correspondents for their interest in our work.1 The debate on adenosine may well be an important factor hampering adoption of physiologically guided revascularization, and therefore the value of a vasodilator-free approach deserves consideration in the light of its possible clinical implications. However, we welcome the criticism employed by the correspondents, as we agree that a rise in adoption must not go hand-in-hand with a fall in accuracy. As such, although our results are favorable, baseline stenosis resistance index (BSR) is still in need of rigorous validation before the concept is of practical value in daily clinical practice.Although we have primarily evaluated the diagnostic accuracy of BSR for ischemia on an independent noninvasive reference standard, the conclusion of Michiels and colleagues that FFR determined in our study was suboptimal is important for the interpretation of our results. However, several aspects contrasting their conclusion need consideration. First, the rate of inaccurate FFR in our study is in accordance with other investigations reporting on this subject within a similarly heterogeneous patient population and noninvasive stress testing as a reference standard.2 Second, the use of low-dose (40 µg maximum) intracoronary adenosine has unequivocally been shown to equal intravenous (IV) (140 µg·kg -1 ·min -1 ) infusion in terms of FFR values.3 Third, all validation studies, evaluating the relation between FFR and myocardial ischemia on noninvasive stress testing, were performed using either low-dose intracoronary or IV adenosine. Both approaches yield equal optimal cut-off values averaging 0.74; a clear indication of their equality. Finally, the search for true maximal hyperemia has indicated that IV adenosine does not induce maximal hyperemia. 4 Hence, one may safely conclude that a direct relationship between FFR and myocardial ischemia is unequivocally determined for both low-dose intracoronary and IV adenosine, whereas neither achieves true maximal hyperemia. Therefore, FFR determined in our study can be considered accurate from a diagnostic point of view and a comparison between FFR and BSR valid.Indeed, the pressure gradient across a stenosis is flow-dependent. Importantly, the relation between this gradient and flow is unique for a given coronary stenosis geometry. This results in a unique and predictable course of this relationship from basal to hyperemic conditions. 5 Combining both pressure and flow information, BSR is a specific characteristic of the stenosis determined during basal conditions, with a high diagnostic accuracy for myocardial ischemia.1 Sen and colleagues interestingly raise the extent of flow velocity as an explanation for the difference in discriminative value between BSR and hyperemic stenosis resistance index. We believe that this difference arises from 2 factors that are indeed related to the extent of flow velocity. First, the presence of a measurement error, which unequivocally accompanies any measurement method, induces a...

Diagnostic Classification of the Instantaneous Wave-Free Ratio Is Equivalent to Fractional Flow Reserve and Is Not Improved With Adenosine Administration

“…However, our results indicate that iFR, FFR, and iFRa had equivalent agreement in diagnostic classification with HSR. This observation is in keeping with other recent independent studies, which have also shown that diagnostic categorization agreement is not necessarily improved after the administration of pharmacological vasodilators (28).…”

The instantaneous wave-free ratio (iFR) for evaluation of non-culprit lesions in patients with acute coronary syndrome and multivessel disease

“…In addition, recent studies found an equivalent agreement between iFR and FFR, when compared to HSR as a standard of reference [40,50]. Accordingly, van de Hoef and colleagues reported the non-hyperemic stenosis resistance index to be as accurate as fractional flow reserve or coronary flow velocity reserve when compared against myocardial perfusion scintigraphy as the standard of reference [51]. Most importantly, an iFR-guided strategy should be compared head to head with a FFR-guided strategy on clinical endpoints.…”

Physiological assessment of coronary lesion severity

“…It has been reported that BSR and FFR have similar levels of diagnostic accuracy for the identification of inducible ischaemia, as established by the area under the curve (AUC) from receiver operating characteristics against myocardial perfusion scintigraphy (AUC 0.77 for both). However, the investigators also suggested that the diagnostic accuracy of BSR was improved (AUC 0.81, P < 0.05) by hyperaemia [hyperaemic stenosis resistance index (HSR)], albeit it is less dependent than FFR on the extent of hyperaemia achieved [19,31]. FFR (cutoff < 0.75) and BSR showed similar false-positive (16 vs. 14%) and falsenegative rates (10 vs. 11%) in this data set.…”

“…The stenosis resistance index is calculated as the ratio of the pressure gradient to the distal flow velocity [19]. It has been reported that BSR and FFR have similar levels of diagnostic accuracy for the identification of inducible ischaemia, as established by the area under the curve (AUC) from receiver operating characteristics against myocardial perfusion scintigraphy (AUC 0.77 for both).…”

“…Adenosine administration is associated with significant, albeit transient, side effects including shortness of breath, flushing, chest pain and AV block, as well as added procedural cost. This has prompted the investigation and development of alternative nonhyperaemic methods of assessing epicardial lesion severity, including the ratio of distal coronary to aortic pressure at rest (P d /P a ) [18], basal stenosis resistance (BSR) [19] and instantaneous wave-free ratio (iFR) [20]. The proponents of nonhyperaemic measurements argue that they reduce, or in some scenarios completely abolish, the need for administration of pharmacological agents, resulting in reduced procedural time and cost, fewer adverse effects and possibly increased adoption by interventional cardiologists [20].…”