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A new method of pressure measurement during the resting phase of the cardiac cycle appears to be as accurate as fractional flow reserve (FFR) in determining the physiological significance of coronary stenoses, according to a study published in the April 2, 2013, issue of the Journal of the American College of Cardiology. Moreover, the novel technique does not depend on administration of a vasodilator, which is required for FFR.

Findings from the CLARIFY trial were presented March 10, 2013, at the American College of Cardiology/i2 Scientific Session in San Francisco, CA.

Investigators led by Sayan Sen, MBBS, of the National Heart and Lung Institute (London, United Kingdom), measured intracoronary pressure and flow velocity distal to the stenosis at rest and during adenosine-mediated hyperemia in 51 vessels of patients scheduled for coronary angiography or PCI. To gauge the hemodynamic severity of lesions, instantaneous wave-free ratio (iFR), adenosine-mediated iFR, and FFR were compared, with the hyperemic stenosis resistance, a combined pressure-and-flow index, as the reference standard.

iFR samples intracoronary pressure during the diastolic ‘wave-free’ period when microvascular resistance is stable and minimized, without induction of hyperemia.

iFR, FFR Mostly Agree

Based on FFR values, almost two-thirds of stenoses fell within the intermediate FFR range of 0.6 to 0.9. In terms of diagnosis, iFR agreed with FFR in 47 of 51 lesions (92.3%). Of the 4 lesions in which the methods disagreed, hyperemic stenosis resistance backed up iFR in 2 of the cases and FFR in the other 2. In all 4 instances, microvascular resistance during iFR was lower than during FFR.

Adenosine-mediated iFR yielded lower median values than either FFR or iFR (0.74 vs. 0.84 and 0.93, respectively; P < 0.001 for both comparisons). Nonetheless, there was no difference in the area under the curve (AUC) values for either iFR or adenosine-mediated iFR compared with FFR (P = 0.15).

Using the established ischemic cutpoint for hyperemic stenosis resistance of > 0.8 mm Hg/cm/s, the relationships of iFR, adenosine-mediated iFR, and FFR to the reference standard were similar (table 1).

Table 1. Diagnostic Performance of Pressure Measurements

^a Based on HSR cutpoint of > 0.8 mm Hg/cm/s.
^b P = 0.48 for difference across methods.

Abbreviations: AUC, area under the curve; HSR, hyperemic stenosis resistance.

The relationship between resting diastolic wave-free microvascular resistance and hyperemic whole-cycle microvascular resistance varied according to stenosis severity. Whereas resistance reduction during iFR rose with increasing stenosis severity, the opposite was true for FFR.

Of note, in almost one-third of stenoses in the intermediate range (FFR 0.6-0.9), microvascular resistance was lower with adenosine-free iFR compared with FFR.

Hyperemic Effect Variable

Across the range of stenoses, adenosine-induced hyperemia with FFR had a more heterogeneous effect on microvascular resistance than the wave-free period used for iFR, with the variability most pronounced for intermediate lesions. Furthermore, although microvascular resistance reduction was statistically greater during adenosine-mediated iFR than standard iFR (75.6% vs. 37.2%; P < 0.001), the reduction was consistent with both methods (P = 0.73) including in the intermediate range of stenoses.

According to the authors, the equivalent diagnostic performance of iFR and FFR seen here is consistent with results of 3 previous studies including more than 700 stenoses (ADVISE, the ADVISE registry, and a prospective trial [Park JJ, et al. EuroIntervention. 2012;130:8]). However, following the “weaker correlation” between the 2 methods in intermediate lesions in the VERIFY trial (Berry C, et al. J Am Coll Cardiol. 2013;61:1421-1427), it was suggested that addition of adenosine to iFR might improve its ability to discriminate among stenoses that do or do not need revascularization.

However, Dr. Sen and colleagues write, “[o]ur findings suggest that hyperemic whole cycle resistance [measured in FFR] is far more variable than resting wave-free resistance” and this variability, which is most pronounced in the intermediate range of stenosis severity, may be “the principal driver of differences between iFR and FFR.” This phenomenon, which was highlighted in data from the DEFER trial, may represent “an inherent limitation of using FFR as a reference standard in this range,” they assert.

Despite greater microvascular resistance reduction with adenosine-mediated iFR, the diagnostic accuracy of the technique was not improved by addition of adenosine, Dr. Sen and colleagues observe. “This suggests that the natural increase in coronary flow velocity and reduction in microvascular resistance during iFR is sufficient in magnitude to assess the fluid dynamics of a stenosis and to accurately differentiate according to severity without the need for adenosine,” they say.

“By obviating the need for vasodilator administration, iFR . . . provides a more consistent assessment across lesions of similar severity,” they add.

iFR May Increase Uptake of Physiologic Lesion Assessment

In an accompanying editorial, Habib Samady, MD, and Bill D. Gogas, MD, of Emory University School of Medicine (Atlanta, GA), identify potential impediments to wider uptake of FFR. In addition to expectations from patients and physicians, as well as incentives to perform revascularization, they observe, “certain practical considerations might dissuade some operators from performing FFR, such [as] the necessity to administer intravenous adenosine that results in frequent, albeit transient, side effects of chest pain, shortness of breath, flushing, or high-degree atrioventricular block, as well as significant added cost.”

The similar diagnostic accuracy of iFR and FFR compared with hyperemic stenosis resistance “is intriguing and highlights the critical importance of the gold standard chosen,” Drs. Samady and Gogas write. “Even if iFR is inferior to FFR, it likely has incremental diagnostic value over visual angiographic lesion assessment, and if more widely adopted in lieu of visual assessment due to its simplicity may result in more appropriate revascularization decisions.”

 

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Sources:
1. Sen S, Asrress KN, Nijjer S, et al. Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration: Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study). J Am Coll Cardiol. 2013;61:1409-1420.

2. Samady H, Gogas BD. Does flow during rest and relaxation suffice [editorial comment]? J Am Coll Cardiol. 2013;61:1436-1439.

 

 

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