Coronary physiology flopped in several studies for determining whether to defer invasive procedures and in optimizing percutaneous coronary intervention (PCI), researchers reported, suggesting there’s more to learn.
“We need to pay more attention to the precise physiology of what we’re measuring and what it means,” said K. Lance Gould, MD, of McGovern Medical School at UTHealth in Houston.
One group found that routine use of computed tomography-derived fractional flow reserve (FFRCT) did not shave healthcare costs in people with stable chest pain, whereas another reported that operators taking extra steps during stenting did not achieve more optimal FFRs after PCI.
Finally, an observational study showed that coronary flow reserve (CFR) couldn’t trump FFR at current thresholds in deciding which patients may defer revascularization.
The three studies were presented during the same late-breaking trial session at this year’s TCT Connect, held virtually by the Cardiovascular Research Foundation.
Resource utilization was about the same whether chest pain clinics in the U.K. adopted routine FFRCT as a frontline test or continued usual care, according to a randomized trial.
Total medical costs — counting the cost of non-invasive cardiac tests, invasive coronary angiography (ICA), revascularization, hospitalization for cardiac events, cardiac medications, and outpatient attendances — averaged £1,605.50 at 9 months for people randomly assigned to frontline FFRCT testing vs £1,491.46 in controls (or median £600 vs £670, P=0.962).
There was no difference between groups in clinical outcomes nor quality-of-life status at that point, according to Nick Curzen, PhD, of the University of Southampton in England.
Thus, the results contradict U.K. guidelines, which recommend coronary CT angiography and HeartFlow FFRCT together as a cost-saving strategy based on National Institute for Health and Care Excellence projections.
FFRCT is FFR derived from coronary CT angiography, thus providing anatomical and physiological information, and is thought to be a safe way to select patients for subsequent invasive testing and treatment of angina.
“The real crux of FFRCT is can it save money? We can, but not by doing it so freely,” Curzen concluded at a press conference.
For the FORECAST study, investigators had 1,400 people presenting to 11 chest pain clinics in the U.K. randomized to the test group getting routine FFRCT or usual care. Median age was around 60 years, and just over half of the participants were men.
Coronary CT angiography use was 96% in the test group and 66% in the reference group. Total ICA tests were 14% lower in the test group (P=0.02), which also had 22% fewer patients undergoing ICAs (P=0.01).
On closer inspection, the test group had coronary CT angiography alone in 64.9% of cases, as most people had no lesions with >40% stenosis. Another 31.5% actually went on to receive FFRCT assessment. None underwent stress echocardiography, perfusion scanning, stress MRI, exercise ECG, or ICA testing.
In contrast, the reference group had patients stop at coronary CT angiography in 61.4% of cases. Dozens received the other non-invasive and invasive tests.
Nevertheless, ICAs and revascularizations were not reduced enough by the FFRCT strategy to make it cost-dominant, Curzen said.
Operators following a physiology-guided incremental optimization strategy did not see an improvement in the number of patients coming out of PCI with optimal FFRs, one center reported.
After angiographically successful PCI, FFR was ≥0.90 in 32% of patients, 0.81-0.89 in 39%, and ≤0.80 in 29%, according to Damien Collison, MD, of Golden Jubilee National Hospital and University of Glasgow in Scotland.
Patients randomized to further intervention to boost FFR wound up with 38.1% achieving FFR ≥0.90, which was statistically no better than the 28.1% of controls (P=0.099). However, the proportion of patients with a final FFR ≤0.80 was lower in the intervention group (18.6% vs 29.8%, P=0.045).
Collison noted that it is rare for operators to assess PCI results using FFR.
“It’s shocking to see so few patients who meet the criteria for optimal physiology at the end of the procedure,” said the moderator of the press conference, Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City.
Chad Rammohan, MD, of Mountain View Center in California, agreed: It’s “a little sobering” to realize that 30% of patients at a good center are still ischemic at the end of PCI, with an FFR below 0.80. The study moves the field toward optimization and using imaging to make PCI results more durable, he said.
The small TARGET-FFR trial was conducted at a single center. Included were 260 people who had angiographically successful PCI before randomization to physiology-guided PCI optimization or usual care.
Operators following the intervention algorithm performed further post-dilation, intracoronary imaging, additional stenting depending on coronary physiology results, and hyperemic pullback assessment.
Further optimization was targeted in 46% of the intervention group. Two-thirds of these patients were deemed appropriate for additional post-dilation and/or stenting.
In these 40 patients who actually received PCI optimization, mean FFR increased from 0.76 to 0.82 (P<0.00) and mean coronary flow reserve was boosted from 3.0 to 4.0 (P=0.02).
Mehran cautioned that perfect is the enemy of the good, as performing extra procedures in PCI may run the risk of cardiac perforation.
FFR-positive patients did not have good clinical outcomes if they had PCI deferred due to a negative CFR result, according to an observational study of combined CFR and FFR assessment.
A treatment algorithm for 455 people with stable coronary lesions dictated that only those who had abnormally low FFR (0.8 or below) and CFR (below 2) would receive PCI, with all others receiving initial medical therapy, Gould reported.
Resulting major adverse cardiovascular events (MACE) rates, counting all-cause death, myocardial infarction, and revascularization, revealed that outcomes were not equal among patients at 2 years:
- Concordant negative (FFR-/CFR-): 5.8%
- Discordant (FFR+/CFR-): 10.8%
- Discordant (FFR-/CFR+): 12.4%
- Concordant positive (FFR+/CFR+): 14.4%
The 10.8% MACE rate of the FFR+/CFR- group was not as good as the 5.8% rate for FFR-/CFR- (P=0.065 for non-inferiority), Gould reported.
“Trust the FFR” was Rammohan’s take-away in discussing the DEFINE-FLOW study at a press conference.
Gould suggested the possibility that reduced FFR and CFR together may still incur additive risk, just at lower thresholds than the ones used for this study. Large randomized trials are needed with thresholds that may actually result in a decrease in morbidity and mortality, he said.
CFR is the ratio between resting and maximal possible coronary blood flow. This measure fails to distinguish flow-limiting stenosis from diffuse or microvascular disease, Gould noted.
Mechanisms controlling coronary blood flow are complex, with physiology differing between the subepicardium and the subendocardium. For instance, high flow may be good for the former but not the latter, he said.
Last Updated October 16, 2020
FORECAST was funded by an unrestricted grant from HeartFlow.
TARGET FFR was funded by the U.K.’s NHS.
DEFINE-FLOW was funded by Philips.
Curzen reported a financial relationship with HeartFlow.
Collison reported financial relationships with Abbott Medical and MedAlliance.
Gould had no disclosures.