NeXT Up: CT-derived FFR Demonstrates Strong Diagnostic Accuracy

Download this article's Factoid (PDF & PPT for Gold Subscribers)

An updated version of noninvasive fractional flow reserve (FFR) based on computed tomography angiography (CTA) data—dubbed FFRCT—shows high diagnostic accuracy, according to a prospective study published online January 29, 2014, ahead of print in the Journal of the American College of Cardiology. With improved specificity, the technology is markedly superior to CTA alone in identifying functionally significant lesions in patients with coronary artery disease (CAD).

Results from the NXT trial were originally presented at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA, in October 2013.

Investigators led by Bjarne L. Nørgaard, MD, PhD, of Aarhus University Hospital Skejby (Aarhus, Denmark), analyzed diagnostic data from 254 patients (484 vessels) with suspected stable CAD at 10 international centers. All patients underwent coronary CTA, invasive angiography, and invasive FFR, which served as the reference standard for significant ischemia at a threshold of 0.80. The results were compared with noninvasive FFRCT values calculated using CTA datasets and the latest computational fluid dynamics software from HeartFlow (Redwood City, CA).

FFRCT Bests CTA for Per-Patient, Per-Vessel Accuracy

Per-patient diagnostic accuracy, as assessed by area under the receiver operating characteristic curve (AUC) in those with stenosis between 30% and 90%, the primary endpoint, was greater with FFRCT compared with CTA (0.90 vs 0.81; P = 0.0008), as was per-vessel accuracy (0.93 vs 0.79; P < 0.0001).

In addition, FFRCT showed accuracy, sensitivity, and specificity levels of 81%, 86%, and 79%, respectively, on a per-patient basis and 86%, 84%, and 86% on a per-vessel basis.

According to the authors, there was good direct correlation of per-vessel FFRCT with FFR (correlation coefficient = 0.82; P < 0.0001), with a slight underestimation by FFRCT compared with FFR. In patients with high calcium levels, the accuracy, sensitivity, and specificity of FFRCT were 75%, 88%, and 69%, respectively, compared with 44%, 94%, and 23% for CTA.

The findings were consistent among patients with intermediate (30%-70%) stenosis (n = 235; table 1).

Table 1. Per-Patient Diagnostic Performance in Patients with Intermediate Stenosis


FFRCT  ≤0.80

CTA >50%

P Value




< 0.0001









FFRCT correctly reclassified 68% of CTA false-positive patients and 67% of CTA false-positive vessels as true negatives with regard to ischemia.

With regard to specificity, the authors assert that the improved diagnostic performance of FFRCT in the present study compared with the earlier DISCOVER-FLOW and DeFACTO trials reflects substantial refinements in FFRCT technology and physiologic modeling, as well as an increased focus on CT image quality and adherence to official recommendations regarding coronary CTA acquisition. 

They note that more than 90% of patients had stenoses of 30% to 70%—the range in which the correlation between angiographic stenosis severity and ischemia is poor and who thus present a particular challenge for clinical decision making. As such, “a single noninvasive test with high diagnostic performance for both anatomy and lesion-specific ischemia would provide a major advantage in assessment of CAD,” the investigators say.

Potential Gatekeeper

The current findings supporting the potential role of CTA with FFRCT as a reliable gatekeeper to invasive angiography and revascularization “may have major health and economic implications,” Dr. Nørgaard and colleagues observe. Insight into the impact of FFRCT guidance on clinical outcomes, resource utilization, costs, and quality of life in patients with suspected CAD will be provided by the ongoing PLATFORM trial, they add.   

In a telephone interview with TCTMD, Robert S. Schwartz, MD, of the Minneapolis Heart Institute Foundation (Minneapolis, MN), called the new results “a big step forward.” FFRCT’s specificity, which has been a problem in the past, is “what is really driving the game, and [the value reported here] bodes very well for this technology,” he added. 

In an accompanying editorial, Harvey S. Hecht, MD, of Mount Sinai Medical Center (New York, NY), observes that FFRCT is “the first noninvasive test to be validated from its inception by an outcome-based gold standard, ie, invasive FFR, rather than one ultimately based on coronary stenosis measurement.” And with the current improved results, FFRCT “appears poised to assume the role of gatekeeper to the interventional laboratory for patients with CTA-defined intermediate stenoses, a role initially envisioned for, but not fulfilled by, CTA alone,” he says.

What’s Next after NXT?

Dr. Hecht highlights a number of issues, though, that shadow the technology’s prospects. For example, current clinical data are limited to 606 patients, and it is unclear whether more research focused on showing FFRCT’s near-equivalence with invasive FFR will be sufficient to advance the strategy or if a randomized outcomes trial will be required.

In a telephone interview with TCTMD, Matthew J. Budoff, MD, of Harbor-UCLA Medical Center (Torrance, CA), said that an outcomes trial, while desirable, is probably not realistic. However, comparative-effectiveness trials pitting FFRCT against nuclear stress testing and conventional angiography are under way, he reported, “and if you can show improved time to diagnosis, lower healthcare cost, and better patient safety, I think that’s a welcome surrogate for a full-blown outcomes study showing superiority.”

Another hurdle for FFRCT will be demonstrating superior cost-effectiveness compared with other noninvasive tests, Dr. Hecht writes. Also, if FFRCT becomes the preferred diagnostic modality, that will have a substantial impact on utilization of other noninvasive functional technologies, resulting in predictable economic consequences.

For the time being, logistical issues such as turnaround time limit application of FFRCT to stable patients, Dr. Schwartz observed, but he predicted that expedited interpretation of CTA data will enable extension of the technology to ACS patients in the future.

“Time will tell whether or not FFRCT will emerge as the gold standard of noninvasive functional testing,” Dr. Hecht concludes. “The initial experience, however, is quite promising, and wide acceptance would indeed be a major ‘game changer.’”


1. Nørgaard BL, Leipsic J, Gaur S, et al. Diagnostic performance of noninvasive fractional flow reserve derived from coronary CT angiography in suspected coronary artery disease: The NXT trial. J Am Coll Cardiol. 2014;Epub ahead of print.

2. Hecht HS. The game changer? J Am Coll Cardiol. 2014;Epub ahead of print.



Related Stories:

NeXT Up: CT-derived FFR Demonstrates Strong Diagnostic Accuracy

An updated version of noninvasive fractional flow reserve (FFR) based on computed tomography angiography (CTA) data—dubbed FFRCT—shows high diagnostic accuracy
  • The study was funded by HeartFlow.
  • Dr. Nørgaard reports receiving research grants from Edwards Lifesciences.
  • Dr. Hecht reports serving as a consultant to Philips Medical Systems.
  • Dr. Budoff reports serving as a consultant to GE Healthcare.
  • Dr. Schwartz reports no relevant conflicts of interest.