Kazumasa Ikeda

Coronary artery disease (CAD) remains the leading cause of death worldwide. Integrating coronary physiology into treatment decision-making is essential to optimize outcomes. Fractional flow reserve (FFR) is the gold standard for assessing the severity of CAD (ischemia) and guiding percutaneous coronary intervention (PCI). However, a single value of FFR cannot capture the spatial distribution of CAD along the vessel. The pullback pressure gradient (PPG) obtained from manual FFR pullbacks is a novel metric for characterizing pressure loss patterns on a continuous scale: values approaching 1.0 represent a focal CAD pattern, whereas values close to 0 represent diffuse disease. PPG predicts flow improvement and angina relief after PCI. This review summarizes the current evidence on PPG and discusses the integration of this novel approach in CAD management.

BACKGROUND: Intravascular imaging (IVI) during percutaneous coronary intervention (PCI) improves outcomes. Pullback pressure gradient characterizes coronary artery disease patterns as focal or diffuse; however, the benefit of IVI across this spectrum remains incompletely understood. We aimed to evaluate clinical outcomes after PCI with or without IVI guidance in patients with focal and diffuse disease defined by pullback pressure gradient. METHODS: Prospective, multicenter, single-arm study of 811 patients (840 vessels) undergoing PCI. Pullback pressure gradient was calculated from manual fractional flow reserve pullbacks to define focal (pullback pressure gradient ≥0.62) or diffuse coronary artery disease. IVI use was at the operator’s discretion. The primary outcome was target vessel failure at 1-year follow-up. RESULTS: IVI-guided PCI was performed in 41% of patients. In the overall cohort, target vessel failure was lower with IVI guidance (adjusted hazard ratio, 0.60 [95% CI, 0.36–0.99]; P =0.044), with a lower incidence of cardiac death ( P =0.042). The results were consistent irrespective of the baseline coronary artery disease pattern ( P _interaction =0.128). Among patients with focal disease, IVI-guided PCI was associated with a significantly lower incidence of target vessel failure compared with non-IVI-guided PCI (hazard ratio, 0.41 [95% CI, 0.18–0.91]; P =0.029). There was no statistical difference in target vessel failure with the use of IVI among patients with diffuse disease (hazard ratio, 0.91 [95% CI, 0.48–1.73]; P =0.771). CONCLUSIONS: In patients undergoing physiology-guided PCI, the use of IVI reduced clinical events at 1 year. These findings suggest that the benefit of IVI extends across the full spectrum of coronary artery disease.

BACKGROUND: The pullback pressure gradient (PPG) is a novel physiological metric that quantifies coronary artery disease patterns as focal or diffuse on a scale from 0 to 1. This study assessed the relationship between PPG and residual angina at 1 year. METHODS: PPG Global is a prospective, investigator-initiated, single-arm, multicenter study that enrolled patients with at least 1 lesion with a fractional flow reserve ≤0.80 intended to be treated with percutaneous coronary intervention. After the PPG calculation, physicians could revise treatment assignment to medical therapy or coronary artery bypass graft surgery instead of percutaneous coronary intervention. Focal and diffuse disease were defined based on the median PPG value of 0.62. Patient-reported outcomes were assessed using the Seattle Angina Questionnaire at baseline and 1-year follow-up. RESULTS: The study included 947 patients with PPG and the Seattle Angina Questionnaire at 1 year. The mean age was 67.6±10.2 years, 24% were female, and 29% had diabetes. At 1 year, patients with focal coronary artery disease reported less angina than those with diffuse disease (Seattle Angina Questionnaire angina frequency score, 95.3±9.9 versus 92.5±15.0; P =0.006). PPG was independently associated with improvement in angina ( P =0.017). CONCLUSIONS: In patients with flow-limiting coronary artery disease, a focal disease pattern defined by high PPG was associated with greater symptomatic relief at 1 year compared with diffuse disease (low PPG). By capturing the underlying pathophysiologic distribution of epicardial disease and its relation to post-treatment symptom relief, PPG may support a more tailored revascularization decision-making and percutaneous coronary intervention strategy.

In patients with stable coronary artery disease (CAD), the long-term benefits of revascularization over medical therapy remain unclear. In the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 trial, patients with hemodynamically significant stenoses (fractional flow reserve (FFR) ≤ 0.80) were randomized to receive FFR-guided percutaneous coronary intervention (PCI) plus medical therapy (n = 447) or medical therapy alone (n = 441). At 5 years, FFR-guided PCI reduced the risk of the primary composite outcome of time to death, myocardial infarction or urgent revascularization, largely because of fewer urgent revascularizations. We now report the long-term clinical outcomes from this trial. Sixteen hospitals, contributing 748 randomized patients (161 women, 21.5%), participated in the long-term follow-up. The primary composite outcome was analyzed hierarchically using the unstratified win ratio, which addressed differential missingness of data on nonfatal outcomes in deceased patients by prioritizing comparisons on time to death. At a median follow-up of 11.2 years, the primary endpoint occurred in 150 of 447 patients (33.6%) in the PCI group versus 182 of 441 (41.3%) in the medical therapy group. PCI was superior in 29.2% of comparisons, medical therapy in 23.3%, and the two groups were tied in 47.5%, resulting in a win ratio of 1.25 in favor of PCI (95% confidence interval (CI) 1.01-1.56, P = 0.043). The corresponding win difference was 5.9% (95% CI 0.2-11.6), and the number needed to treat was 17 (95% CI 9-500). Win ratios were 0.88 for all-cause death (95% CI 0.66-1.17), 1.50 for myocardial infarction (95% CI 0.98-2.31) and 4.57 for urgent revascularization (95% CI 2.53-8.24). During long-term follow-up, FFR-guided PCI in patients with stable CAD and hemodynamically significant stenoses reduced the composite of death, myocardial infarction or urgent revascularization, primarily because of fewer urgent revascularizations. These long-term findings reaffirm the efficacy of FFR-guided PCI over medical therapy in patients with stable CAD. ClinicalTrials.gov registration: NCT06159231 .

BACKGROUND: Impaired flow following percutaneous coronary intervention (PCI) is a known predictor of adverse outcomes. The pullback pressure gradient (PPG) is a novel physiological metric that differentiates focal from diffuse disease and enables prediction of post-PCI fractional flow reserve (FFR). This post hoc analysis of the PPG Global (NCT04789317) study aimed to evaluate the prognostic performance of a PPG model for predicting post-PCI FFR and to determine whether the predicted physiological outcome is associated with adverse events following PCI. METHODS: Prospective and multicenter study including patients with hemodynamically significant coronary artery disease undergoing PCI. A prediction model based on FFR and PPG was used to estimate post-PCI FFR. Based on the predicted values, vessels were classified as having either optimal or suboptimal post-PCI physiology. The primary end point was target vessel failure at 1 year. Target vessel failure was defined as a composite of cardiac death, target-vessel myocardial infarction, and ischemia-driven target vessel revascularization. RESULTS: A total of 855 patients (890 vessels) were analyzed. The mean difference between predicted and measured post-PCI FFR was 0.001 (limits of agreement, –0.10 to 0.10). There was a strong correlation between predicted and measured delta FFR ( r =0.92 [95% CI, 0.91–0.93]; P P =0.004). Predicted suboptimal physiology was independently associated with adverse clinical outcomes. CONCLUSIONS: PPG-predicted post-PCI physiology was associated with target vessel failure at 1 year. These findings extend the role of coronary physiology beyond diagnostic assessment to include risk stratification and outcome prediction following PCI.

Background: Sex differences in coronary artery disease (CAD) have been increasingly recognized, as women present with distinct clinical characteristics and outcomes compared with men. This study investigated the impact of sex on pathophysiological CAD patterns (focal versus diffuse) in stable patients undergoing percutaneous coronary interventions (PCI). Methods: We conducted a subanalysis of the PPG Global (Pullback Pressure Gradient Global Registry) study, a multicenter, prospective trial including 993 patients (236 [23.8%] women and 757 [76.2%] men) with hemodynamically significant CAD, defined as fractional flow reserve ≤0.80. The pullback pressure gradient metric categorized CAD patterns as focal or diffuse. Patient‐reported outcomes were collected using the 7‐item Seattle Angina Questionnaire. Optimal revascularization was defined as post‐PCI fractional flow reserve ≥0.88. Results: Women were significantly older than men, with a mean age of 69.8±10.3 years compared with 67.0±10.1 years ( P P =0.093), women reported more severe symptoms compared with men, as reflected in the Seattle Angina Questionnaire‐7 angina frequency score (mean 76.7±22.9 versus 81.5±20.3, P =0.002). Women exhibited a more focal CAD pattern (pullback pressure gradient 0.65±0.16 versus 0.61±0.16, P =0.001) and achieved higher post‐PCI fractional flow reserve values (0.88±0.07 versus 0.87±0.07, P =0.02). Women undergoing PCI had a higher rate of optimal revascularization (54% versus 44%, P =0.01). Conclusions: This study reveals clinically significant differences in CAD patterns between sexes, with women demonstrating a higher burden of angina, more focal disease distribution, and better physiological results after PCI.