Physiologic Testing May ID Patients Who’ll Still Have Angina After PCI

The findings imply a role for FFR in determining which patients may not get symptom relief from an intervention.

Physiologic Testing May ID Patients Who’ll Still Have Angina After PCI

Patients with more-severe physiologic lesions prior to PCI tend to get more symptomatic relief from the procedure, and larger improvements in fractional flow reserve (FFR) after stenting are associated with more relief from angina and improved quality of life, according to an analysis of the TARGET-FFR study.

Researchers say intracoronary physiologic assessments can help inform patient expectations about the benefits of PCI, and may even be used to take the patient off the table if FFR suggests that putting in a stent won’t help their symptoms. Explaining why FFR is being used at the outset might help to manage patient expectations, too.

“If you appropriately discuss the procedure as more of an assessment rather than a definite PCI, then their expectation going into it will be to learn if they need or will benefit from a stent,” lead investigator Damien Collison, MBBCh (Golden Jubilee National Hospital, Glasgow, Scotland), told TCTMD. “That up-front management of expectations in terms of what we might find and might do is probably a better way to go, particularly for a procedure where the goal is alleviating their symptoms of stable angina. You really want to know or be able to reassure them that what you’re going to do is going to be effective. It’s not an insignificant lifetime risk of putting in a stent that’s not going to make them feel better or improve their quality of life.”

The persistence of angina after PCI is not an uncommon problem, with data suggesting that anywhere from 20% to 50% of patients still have symptoms postprocedure. In contemporary studies with systematic follow-up using standardized tools, roughly one-third of patients will have symptoms after PCI, said Collison. Knowing who won’t benefit from treatment would help prevent unhelpful stenting, but how to single out those patients is unclear.

Bigger Change in FFR Yields Improved Symptoms

The goal of the present study, published in the April 2023 issue of Circulation: Cardiovascular Interventions, was to identify different patient and procedural predictors of angina after PCI. The analysis included 230 patients in the TARGET-FFR trial testing angiography versus FFR to optimize PCI.

Of these patients, 38.3% had angina after PCI as determined by the Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score. Those with angina after PCI had higher rates of previous MI and PCI, as well as a higher prevalence of atrial fibrillation and current smoking. They were also prescribed more antianginal medications, including oral nitrate tablets and reliever sublingual nitrate spray. Patients with angina after PCI also had significantly higher SAQ summary scores and worse quality of life before the procedure compared with those who responded well to treatment.

“From a clinical point of view, we’ve identified—not necessarily causation but an association—certain features where we can say, perhaps, this is a person who may have residual angina,” said Collison. “However, the real kernel of the study is when we brought them forward to the pre-PCI physiology assessment.”  

Patients who were angina-free at 3-month follow-up had more physiologically severe lesions prior to PCI. For example, those with no angina after PCI had a preprocedure FFR of 0.56 compared with 0.62 in those with symptoms after the procedure (P = 0.003). Coronary flow reserve and Pd/Pa (the ratio of resting distal coronary to aortic pressure) prior to PCI also were lower, indicative of more severe lesions, in those without angina after PCI.

In terms of changes with PCI, those with postprocedure angina had less improvement in FFR (mean 43.1 vs 67.0; P < 0.001). In multivariate modeling, a smaller improvement in FFR after PCI was independently associated with postprocedure angina.

Clinical Implications?    

Robert Byrne, MBBCh, PhD (Mater Private Hospital, Dublin, Ireland), who wasn’t involved in the study, said that a large proportion of their work in the cath lab is targeted at reducing symptom burden and improving quality of life.

“In our practice, we see all our patients back for a 6-week checkup, [and] certainly we are pleased to hear that in the vast majority of cases patients feel significantly better and have less limitation in doing the activities that they enjoy on a day-to-day basis,” he told TCTMD in an email. “However, we also realize that post-PCI angina is an issue not infrequently encountered in clinical practice.”

The causes of angina after a procedure are varied and complex, said Byrne, and may include residual symptoms in the target vessel or another artery, suboptimal procedure, or microvascular angina, which can be present even when epicardial coronary artery stenosis is triggering the angina symptoms.   

As for the clinical implications of the current TARGET-FFR analysis, Byrne was uncertain. “Certainly, chasing a given number for postprocedure FFR may not be a strategy that yields fruit and the potential for adverse impact needs to be considered,” he said. “In addition, any metric that focuses on postintervention FFR is less likely to be helpful for clinicians, because at that stage the ship has sailed and a potentially unhelpful intervention has not been avoided.”

Green May Not Always Mean Go

To TCTMD, Collison said the study may suggest a need to move away from using FFR as a “traffic light” to proceed with stenting, noting that an FFR ≤ 0.80 should not necessarily be the benchmark for PCI. Instead, physicians should use their clinical judgement when trying to determine if the patient will benefit. 

It’s not an insignificant lifetime risk of putting in a stent that’s not going to make them feel better or improve their quality of life. Damien Collison

“For example, [say] there’s flow limitation in this vessel, but it’s a completely diffuse gradient,” said Collison. “Putting a long stent in is really not going to move the needle in terms of physiologic improvement or response. That’s probably the key physiologic finding from the paper—if you’re only making a small marginal gain in physiology—the delta in FFR—then the likelihood is the patient is going to have persistent angina, particularly if they have more-severe and prominent symptoms coming into the procedure.”     

Collison noted that patients who reported the most severe and frequent angina tended to have less physiologically severe lesions, which was surprising.

“If you’re finding that disconnect between lesion severity and focality, which is where PCI will really work, and the patient’s symptoms, that’s probably a case where you can say to them, ‘Technically, I can put a stent in but there’s a good chance it’s not going to alleviate your symptoms,’” said Collison. “The striking thing about that was that if patients had any angina after their procedure, their quality-of-life score was exactly the same. It didn’t change at all. That’s kind of sobering.”

While every patient in TARGET-FFR had flow-limiting coronary artery disease, it’s possible not all of their symptoms were related to the lesion, he added. Interestingly, 6% of patients reporting angina symptoms after stenting had no symptoms before PCI. This finding, say investigators, highlights the importance of ascertaining the indication for PCI and the appropriateness of the procedure, especially since symptom relief is the primary reason for intervening in stable patients.


In an editorial, Nathaniel Smilowitz, MD (NYU Langone Health, New York), and Arnold Seto, MD (VA Long Beach Health Care System, CA), say the study emphasizes the importance of coronary physiology to select patients with hemodynamically significant lesions for PCI.

It also raises the question whether operators should optimize PCI by striving for a goal FFR > 0.90 postprocedure, given that larger improvements in hyperemic coronary pressure ratios led to greater antianginal benefits. The main TARGET-FFR trial specifically tested that premise, however, and failed to demonstrate an improvement in outcomes with physiologic optimization, write Smilowitz and Seto. That trial had limitations, though, with optimization only attempted in 31% of cases because of the presence of diffuse disease. DEFINE-GPS, an ongoing study also testing physiologic optimization, will shed some further light on this topic.

“The results of this trial will determine whether more aggressive PCI can be more effective in angina relief, or whether diffuse coronary artery disease will always thwart a focal revascularization technique,” write Smilowitz and Seto.

Michael O’Riordan is the Associate Managing Editor for TCTMD and a Senior Journalist. He completed his undergraduate degrees at Queen’s…

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  • Collison reports consulting for Abbott.
  • Smilowitz reports honoraria from Abbott Vascular.
  • Seto reports research grants from Acist and Philips and consulting honoraria from Janssen, Terumo, GE Healthcare, and Cordis. He holds equity in Frond Medical.