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  • After PCI, Residual Angina More Common in Diffuse vs. Focal CAD – TARGET-FFR Substudy

    The baseline pattern of coronary artery disease (CAD) can predict the likelihood of angina relief, according to a new study, which showed that residual angina after percutaneous coronary intervention (PCI) is almost twice as common in patients with diffuse disease, whereas patients with a focal disease have greater improvement in angina and quality of life.

    These findings from the TARGET-FFR trial were reported in a manuscript published Wednesday online in JACC: Cardiovascular Interventions, with authors led by Carlos Collet MD, PhD, from OLV Hospital, Aalst, Belgium; Damien Collison, MBBCh, of Golden Jubilee National Hospital, Clydebank, and the University of Glasgow, both in Scotland; and Takuya Mizukami, MD, PhD, of OLV Hospital and Showa University, Tokyo.

    An increase in fractional flow reserve (FFR) after PCI is associated with improvement in angina. CAD patterns (focal vs. diffuse) influence the FFR change after stenting and may predict angina relief. A pressure pullback maneuver could quantify the longitudinal distribution of epicardial resistance. The pullback pressure gradient (PPG) is a novel metric that complements FFR and quantitatively defines CAD patterns (focality or diffuseness) on a scale from 0 to 1. High PPG is interpreted as focal disease and low PPG as diffuse disease, the authors wrote.

    Between Feb. 22, 2018, and Nov. 22, 2019, 721 patients were screened, and 260 were randomized; among these, 190 patients had pre-PCI FFR pullback. After excluding pullback recordings of inadequate quality and patients without health status questionnaires at follow-up, 103 patients (51 with focal and 52 with diffuse disease) were included in the analysis.

    FFR measurements were performed using the Pressure Wire X Guidewire (Abbott Laboratories). After the administration of a 200-mg bolus of intracoronary nitrate, the pressure wire sensor was positioned at the tip of the guide catheter and equalized with the aortic pressure. The pressure wire was then advanced to position the sensor in the distal third of the vessel. Hyperemia was induced by adenosine infusion into an antecubital vein at a rate of 140 mg/kg/min. Coronary flow reserve (CFR) was assessed using the bolus thermodilution technique. FFR pullback maneuvers were performed manually at a constant speed for 20 to 30 seconds.

    The primary outcome was the seven-item Seattle Angina Questionnaire (SAQ-7).

    There were no differences in the baseline characteristics between patients with focal and diffuse CAD. Overall, 13.6% of patients were female, their mean age was 60.61 ± 8.11 years, their mean body mass index was 29.39 ± 4.62 kg/m2, 68% had a family history of CAD, 68% had a history of smoking, and 56.3% had dyslipidemia.

    Patients with focal disease saw larger increases in FFR after PCI than patients with diffuse disease (0.30±0.14 vs 0.19±0.12; P < 0.001). Patients with focal disease who underwent PCI for focal CAD had significantly higher SAQ-7 summary scores at follow-up than those with diffuse CAD (87.1±20.3 vs 75.6±24.4; mean difference = 11.5 [95% CI: 2.8-20.3]; P = 0.01). After PCI, residual angina was present in 39.8% of the patients but was significantly less in those with treated focal CAD (27.5% vs 51.9%; P = 0.020).

    Residual angina after PCI was frequent and predominantly observed in patients with diffuse CAD as defined by the pre-PCI PPG. Patients with focal disease reported greater improvement in angina and quality of life with PCI. The PPG identified patients most likely to benefit from PCI in terms of angina relief. The writers suggested that the distribution of the epicardial resistance should be factored into the clinical decision-making process about the appropriateness and the modality of revascularization. They said a randomized clinical trial assessing the clinical and economic impact of a PPG-guided PCI strategy is warranted.

    Patrick W. Serruys MD, PhD, and colleagues, from the National University of Ireland, Galway, , suggested in an accompanying editorial that noninvasive imaging may soon take the baton from conventional angiography because it delivers luminograms, intravascular ultrasound–like vessel wall imaging, and possibly, assessment of microvascular resistance.

    The editorial comment also suggests clinicians should investigate the possibility of angina or ischemia without obstructive CAD.

    “Microspasms elicited by the direct cholinergic effect of acetylcholine through altered and sick permeable endothelium with poor cell interconnectivity (insufficient cadherin and protein 120), structural and functional dysfunction of microvascular circulation, caused or accompanied by nitric oxide synthetic activity that results in exercise-induced coronary insufficiency and induced ischemia are all mechanisms to be investigated on top of epicardial conductance,” the editorialists wrote. “That makes the job of interventional cardiologists more complex as they explore the labyrinth of physio-pathological mechanisms of residual angina.”

    Future studies, including COURAGE II, ORBITA II and ISCHEMIA II, will compare optimal medical therapy (OMT) alone to revascularization plus OMT. The expert commenters wrote that these studies must include in their screening and protocol the assessment of focality and diffuseness as well as the detection of dysfunction of microvascular circulation.

    The editorialists concluded that future OMT for patients with diffuse CAD will not be restricted to “symptomatic” drugs, such as beta-blockers or nitrate, “but also powerful antiatherogenic drugs – for example, micro-RNA, anti-PCSK-9 production, lipoprotein (a), high-sensitivity C-reactive protein, ligand against IL-6 – which are able to reverse the diffuse atherosclerotic process.”


    Collet C, Collison D, Mizukami T, et al. Differential Improvement in Angina and Health-Related Quality of Life After Percutaneous Coronary Interventions in Focal and Diffuse Coronary Artery Disease. JACC Cardiovasc Interv. 2022 Nov 29 (Article in press).

    Serruys PW, Kageyama S, Garg S, et al. In the Beginning There Was Angina Pectoris, at the End There Was Still Angina Pectoris. JACC Cardiovasc Interv. 2022 Nov 29 (Article in press).

    Image Credit: Katleho Seisa/ –

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