Clinical validation of the resting pressure parameters in the assessment of functionally significant coronary stenosis; results of an independent, blinded comparison with fractional flow reserve

doi:10.1016/j.ijcard.2013.07.030

International Journal of Cardiology

Volume 168, Issue 4, 9 October 2013, Pages 4070-4075

https://doi.org/10.1016/j.ijcard.2013.07.030 Get rights and content

Abstract

Background

The role of resting pressure parameters, i.e. instantaneous wave-free ratio (iFR), and resting distal coronary pressure/aortic pressure (Pd/Pa) in assessing functionally significant stenosis remains controversial. We sought to assess the diagnostic performance of iFR and resting whole-cycle Pd/Pa in Asian patients.

Methods

In this study, 238 consecutive lesions (no total occlusions) in which fractional flow reserve (FFR) was measured with both intravenous and intracoronary adenosine administration were included. Coded resting pressure data were sent to the core laboratory in which iFR was calculated in a blinded fashion.

Results

FFR and iFR had unimodal distributions and the correlation was r = 0.77 (95% confidence interval, 0.71 to 0.82). In a receiver-operating-characteristic curve analysis, iFR had an area under the curve (AUC) of 0.9 at FFR ≤ 0.80. The best cut-off value for iFR was 0.90 with a sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 76%, 86%, 82% and 80%, and 82%, respectively. The resting whole-cycle Pd/Pa cut-off of 0.91 demonstrated a diagnostic accuracy of 82% (AUC 0.9). However, iFR had higher discriminatory power than the resting whole-cycle Pd/Pa.

Conclusion

Both iFR and resting whole-cycle Pd/Pa showed good diagnostic performance to define the functionally significant stenosis in an independent Asian cohort distributed unimodally and without total occlusions. However, further validation is needed to explore the areas of disagreement between different physiologic parameters prior to adoption of resting pressure parameters into routine clinical practice.

Introduction

The revascularization of patients with objective evidence of ischemia can improve functional status and outcomes [1], [2], [3], and fractional flow reserve (FFR) is a proven physiologic tool for assessment of lesion specific ischemia. FFR-guided percutaneous coronary intervention (PCI) can improve the event free survival, and reduce health care costs [3], [4], [5]. FFR calculation requires the administration of potent coronary vasodilator such as adenosine, a process which aims to minimize coronary resistance to allow a linear relationship between pressure and flow [6].

Recently, Sen et al. proposed a new pressure-derived physiologic index from coronary wave-intensity analysis, the instantaneous wave-free ratio (iFR), which does not require adenosine for its calculation [7]. iFR relies on the identification of a wave free period in diastole when distal coronary resistance is intrinsically stable within the cardiac cycle. In the ADVISE study, iFR demonstrated diagnostic accuracy of 88% in defining the presence of myocardial ischemia. However, there has been debate on the accuracy and clinical usefulness of this novel index [8], [9]. Moreover, its relationship with resting pressure ratio has not been clearly defined yet.

In the present study, we aim to test the diagnostic performance of iFR in an independent cohort of Asian patients with intermediate stenosis whose FFR was measured with at least 2 different methods of hyperemia and to investigate the relationship between the resting whole-cycle Pd/Pa ratio and iFR.

Section snippets

Study population

FFR had been measured in consecutive patients at Seoul National University Hospital and Keimyung University Dongsan Medical Center, which are university hospitals with large PCI volumes. For the current analysis, 243 consecutive, predominantly intermediate lesions on coronary angiogram with FFR measurement with both intracoronary bolus and intravenous adenosine were selected from the FFR database. Patients were excluded if any of the following was present: in-stent restenosis, acute ST-segment

Population characteristics

The study population was formed predominantly by physiologically intermediate stenosis (Fig. 2). Mean FFR was 0.81, with 72% of the FFR values falling between 0.7 and 0.9. Only 26% of the stenoses had an FFR value ≤ 0.75. The baseline clinical characteristics and angiographic findings are summarized in Table 1. The mean age of the study population was 63 years, 68% were male, 28% had diabetes mellitus and 63% had dyslipidemia. Most patients presented with stable angina (63%), and most lesions

Discussion

In this study, we evaluated the diagnostic performance of iFR and resting whole-cycle Pd/Pa in an independent cohort of Asian patients with intermediate stenoses in whom FFR was measured by both intracoronary bolus administration and intravenous continuous infusion of adenosine. There are several strengths in this study. First, we performed the FFR measurement with at least two different methods of hyperemia. Second, the whole analysis was performed in a blinded fashion and iFR was calculated

Conclusions

In an independent clinical cohort of patients with intermediate coronary stenoses, both iFR and resting whole-cycle Pd/Pa demonstrated a good diagnostic agreement with FFR, when calculated in a blinded fashion and using the same algorithm applied to the ADVISE studies. However, iFR had higher discriminatory power than resting whole-cycle Pd/Pa. Further validation is needed to explore the areas of disagreement between different physiologic parameters prior to adoption of iFR into routine

Disclosures

Dr. Davies holds patents pertaining to this technology.

Acknowledgment

This study was supported by a grant from the Innovative Research Institute for Cell Therapy and the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A062260).

References (11)

P.A. Tonino et al.
Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation
J Am Coll Cardiol
(2010)
S. Sen et al.
Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study
J Am Coll Cardiol
(2012)
W. Rudzinski et al.
Instantaneous wave-free ratio and fractional flow reserve: close, but not close enough!
J Am Coll Cardiol
(2012)
L.J. Shaw et al.
Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy
Circulation
(2008)
R.F. Davies et al.
Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization
Circulation
(1997)

There are more references available in the full text version of this article.

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Clinical validation of the resting pressure parameters in the assessment of functionally significant coronary stenosis; results of an independent, blinded comparison with fractional flow reserve

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Population characteristics

Discussion

Conclusions

Disclosures

Acknowledgment

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy

Circulation

Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization

Circulation