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

Abstract

Background

Adenosine administration is currently required for evaluation of stenosis severity with fractional flow reserve (FFR). The instantaneous wave-free ratio (iFR) was recently introduced as an adenosine-free alternative in patients with stable CAD. The aim of the present study was to replicate the findings of previous iFR studies using an independent calculation algorithm and to evaluate the iFR for the assessment of non-culprit vessels in patients with acute coronary syndrome (ACS).

Methods and results

53 patients with ACS (65%) and at least one non-culprit intermediate lesion and 29 (35%) with stable CAD were included. A total of 123 stenoses were evaluated with both FFR and iFR. Classification match of iFR in ACS was not inferior to stable CAD (79.5% in ACS and 84.4% in CAD; p = 0.497). Accordingly, no difference was observed in iFR/FFR correlation between ACS and stable CAD (r = 0.66 in ACS vs. r = 0.69 in CAD). Overall, a significant correlation was found between iFR and FFR (r = 0.68; p < 0.001) with a good diagnostic efficiency at ROC analysis (area under the curve: 0.87). In addition, neither the localization of the stenosis within the coronary tree (p = 0.147) nor the time interval from the acute event (p = 0.550) significantly influenced the concordance of iFR with FFR.

Conclusions

The iFR is a promising method for the assessment of non-culprit lesion severity in patients with acute coronary syndrome.

Introduction

It is well-known that coronary angiography has several limitations, especially in the evaluation of intermediate stenoses [1], [2]. Additional limitations are associated with the presence of multiple, long or irregular stenoses, affecting distal coronary blood flow and resistance [3].

For these reasons, several methods for the functional assessment of stenoses have been proposed. Currently, the best technique to assess stenosis severity in the catheterization laboratory is fractional flow reserve (FFR), calculated as the distal to proximal (aortic) pressure ratio during hyperemia [4]. Since several studies demonstrated the clinical benefit of FFR-guided interventions on patients' outcomes [5], [6], [7], the 2009 Focused Updates to the ACC/AHA/SCAI Guidelines on PCI increased the “level of evidence” for FFR to an “A” level, definitively stating that FFR is valuable to detect significant coronary stenoses [8].

However, despite this body of evidence, the current use of FFR remains rather low worldwide, mainly because of the lack of device reimbursement in many countries [9], [10], [11], [12], [13]. Other potential reasons that might dissuade some operators from performing FFR are uneasy access to adenosine or other vasodilator drugs at proper concentration, seemingly prolongation of procedural time, and contraindication to adenosine administration in patients with asthma, COPD or bradycardia [14].

In an attempt to overcome those restraints, an alternative adenosine-free index of coronary stenosis, the instantaneous wave-free ratio (iFR), was recently introduced in patients with stable coronary disease to assess the stenosis severity [15], [16], [17], [18], although the value of this index has been questioned [19], [20]. An independent, core laboratory-based analysis of all previous studies showed a classification match between 80 and 88% [21].

Assessment of non-culprit stenoses after treatment of the culprit vessel is an important issue in patients with acute coronary syndrome (ACS). In fact, the decision on the treatment of non-culprit vessels is always challenging, especially in patients with multivessel disease and intermediate stenoses [22], [23], [24]. In this regard, the use of intracoronary pressure indices would provide a complete and rapid assessment of all non-culprit lesions eventually present, allowing the identification of all ischemia-causing stenoses before the patients leave the catheterization laboratory, potentially avoiding a second procedure. Immediate diagnosis of non-culprit significant stenoses during the primary intervention gains even more importance in light of the recently published PRAMI trial, showing that PCI of non-culprit vessels in STEMI patients significantly reduces the incidence of adverse cardiovascular events during the follow-up, as compared with PCI limited to the infarct artery [25]. Several hemodynamic and physiological alterations are observable during ACS which could influence intracoronary pressure, as variations in the adrenergic state, myocardial oxygen consumption and flow. However, despite FFR measurement during acute myocardial infarction has been already evaluated by Ntalianis and colleagues, reporting that measurement of FFR in non-culprit vessels is reliable in such setting [26], no data is available on feasibility and reliability of iFR in the same clinical setting. However an instantaneous, adenosine-free pressure-derived functional index would be most helpful in this clinical context. Accordingly, the aim of the present “FORECAST” study was to test whether previous results on trans-stenotic instantaneous wave-free ratio (iFR) could be replicated with an independent calculation algorithm based on the original definition. Finally and foremost, we aimed at evaluating the iFR classification match with FFR for the assessment of non-culprit vessels in ACS patients with multivessel disease.