Pd/Pa vs iFR™ in an Unselected Population Referred for Invasive Angiography

Title:

A comparative study of resting Pd/Pa, instantaneous wave-free ratio and fractional flow reserve in an unselected population referred for invasive angiography.

Instantaneous wave-free ratio (iFR™) is a novel non-hyperaemic index for assessing the functional significance of a coronary stenosis without coronary vasodilatation. In previous studies it has been compared to the hyperaemic index FFR with variable results. As a guide to determining the need for revascularisation it has been employed using a dichotomous cut-off without FFR or within a hybrid strategy in which lesions with intermediate iFR™ values are further interrogated using FFR.

The comparative diagnostic utility of iFR™ vs resting pressure (Pd/Pa) in reference to FFR is uncertain. We plan to undertake a prospective clinical study in consecutive patients undergoing clinically-indicated FFR assessment in the cardiac catheterisation laboratory with 30-80% diameter stenosis on quantitative coronary angiography (QCA). We will will use a proprietary (Volcano) pressure wire system and iFR ™ algorithm in order to calculate iFR™ and Pd/Pa in both resting and hyperemic conditions as well as FFR.

The sample size is 260 vessels and the enrolment period is 18 months. Hyperaemia will be induced by intravenous adenosine (140 ug/kg/min) administered wherever possible via an antecubital vein. Intra-coronary nitrates will also be given in line with the standard care procedure for FFR measurement.

Design:

In this prospective single centre cohort study all consecutive patients undergoing FFR are eligible for inclusion.

Active Hypothesis: (1) In comparison to an FFR for all strategy, revascularisation decisions made using binary cut-off values of iFR™ or resting Pd/Pa will result in similar levels of disagreement.

Active Hypothesis: (2) In comparison to an FFR for all strategy, revascularisation decisions using hybrid strategies incorporating iFR™ or resting Pd/Pa and FFR will result in similar levels of disagreement.

Active Hypothesis (3): Compared to iFR™ measured under resting conditions, hyperaemic iFR™ has a stronger correlation with FFR. Should this be the case, then the diagnostic efficiency of iFR™ can be interpreted as being improved with pharmacological vasodilatation. The null hypothesis is that there is no difference in diagnostic efficiency between iFR™ and hyperaemic iFR compared to FFR.

The clinical decisions in the catheter laboratory will align with routine care and be informed by all available clinical data and the FFR results.

This study is being conducted independently in the National Health Service without industry support or involvement.

Sample size: 260 vessels.

Statistical Analysis: Independent analysis of the completed dataset will be performed by Dr John McClure a biostatistician and lecturer in the Institute of Cardiovascular and Medical Sciences in Glasgow.

Methods: We will measure resting indices Pd/Pa and iFR™. Following this we will then measure hyperaemic readings including FFR and hyperaemic iFR™ (HiFR) sequentially using peripherally administered adenosine. Upon completion of enrollment we will produce summary statistics describing demographics and procedural data for the study cases. We will then calculate the discriminatory power of iFR™ using both the pre-specified binary cut-off values of 0.90 for iFR™ and 0.92 for resting Pd/Pa and the adenosine zones for iFR of 0.86-0.93 and resting Pd/Pa of 0.87-0.94. We will also analyse the correlation of HiFR with FFR

Inclusion criteria

All patients ≥18 years of age, already undergoing pressure wire assessment and able to consent

Exclusion criteria

Inability to receive adenosine

Extremely tortuous vessels

Highly calcified lesions unsuitable for pressure wire assessment

coronary artery occlusion

acute MI within 3 days