The use of invasive coronary flow reserve (CFR) thresholds of 2.0 or greater to defer revascularization for lesions with reduced fractional flow reserve (FFR), and where percutaneous coronary intervention (PCI) is clinically indicated, should be avoided, according to new data.
Published online Monday and in the Sept. 13 issue of JACC: Cardiovascular Interventions, the study noted that since its introduction in 1974, CFR has had “a profound scientific impact” and formed the conceptual basis for myocardial perfusion imaging. However, the current role for invasive CFR assessment remains unclear since FFR has become the reference standard.
Led by Nils P. Johnson, MD, MS, from the McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, the team said that although observational data from invasive and noninvasive tools indicate that intact CFR carries a favorable prognosis, such studies did not simultaneously assess FFR.
Further, they noted that because of fundamental physiological relationships, combined measurement of CFR and FFR leads to disagreement in approximately 40% of cases when using traditional binary thresholds.
“Do such discordances matter? Perhaps lesions with intact CFR can be treated medically despite reduced FFR,” said Johnson and colleagues.
“Alternatively, lesions with intact FFR but reduced CFR might have worse outcomes or more symptoms,” they suggested.
To address the clinical uncertainties surrounding the relationship and value of using both FFR and XFR, the team designed and carried out the DEFINE-FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect–Combined Pressure and Doppler Flow Velocity Measurements) study.
“We hypothesized that initial medical treatment for lesions with reduced FFR ≤0.8 but intact CFR (≥2.0) would result in noninferior 2-year clinical outcomes compared with lesions with preserved FFR and CFR,” said the authors.
Johnson and colleagues analyzed data from 455 subjects with 668 lesions who were enrolled from 12 sites in six countries. Of the 668 lesions in the study, 14% had FFR ≤0.8 but CFR ≥2.0, while 23% had FFR >0.8 but CFR <2.0.
During a two-year follow-up, the primary endpoint of composite all-cause death, myocardial infarction or revascularization in lesions with FFR ≤0.8 but CFR ≥2.0 (10.8% event rate) compared with lesions with FFR >0.8 and CFR ≥2.0 (6.2% event rate) exceeded the prespecified +10% noninferiority margin (P = 0.090), said the authors.
They noted that target vessel failure (TVF) models using both continuous FFR and continuous CFR found that only higher FFR was associated with reduced target vessel failure (Cox P = 0.007) after initial medical treatment.
“These results do not support using invasive CFR ≥2.0 to defer revascularization for lesions with reduced FFR if the patient would otherwise be a candidate on the basis of the entire clinical scenario and treatment preference,” said Johnson and colleagues.
A multitude of measures
Writing in an accompanying editorial, Bon-Kwon Koo, MD, PhD, and Seokhun Yang, MD, from Seoul National University Hospital, South Korea, said the team behind the DEFINE FLOW study should be congratulated on the completion of the study, “which will be a standard reference for future investigations.”
However, they noted that CFR is just one of a multitude of measures that can be undertaken during a comprehensive physiological assessment in the cardiac catheterization lab.
“We are literally living in the abundance of a physiological-assessment civilization,” they said.
“As expected, more measurements generate more discordances for which more data and knowledge are still needed to make appropriate interpretation and decisions for treatment.”
The editorialists added that it is also important to consider the take-home message of a study and not let results “simply push us to leave the cradle of civilization and move to a new world.”
“In other words, these results can be interpreted in a more pragmatic way considering the unique features of CFR and FFR,” they said, noting that CFR represents not only the ratio of hyperemic flow to resting flow, but also the whole coronary circulation system’s ability to respond to various resting and hyperemic stimuli.
Johnson NP, Matsuo H, Nakayama M, et al. Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses. JACC Cardiovasc Interv 2021;14:1904-1913.
Koo B-K, Yang S. Look at the Moon, Not the Finger Pointing to It. JACC Cardiovasc Interv 2021;14:1914-1916.
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