Clinical Impact of Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve on Japanese Population in the ADVANCE Registry

Abstract

Background: Coronary computed tomography angiography (cCTA)-derived fractional flow reserve (FFR_CT) is a promising diagnostic method for the evaluation of coronary artery disease (CAD). However, clinical data regarding FFR_CT in Japan are scarce, so we assessed the clinical impact of using FFR_CT in a Japanese population.

Methods and Results: The ADVANCE registry is an international prospective FFR_CT registry of patients suspected of CAD. Of 5,083 patients, 1,829 subjects enrolled from Japan were analyzed. Demographics, symptoms, cCTA, FFR_CT, treatment strategy, and 90-day major cardiovascular events (MACE) were assessed. Reclassification of treatment strategy between cCTA alone and cCTA+FFR_CT occurred in 55.8% of site investigations and in 56.9% in the core laboratory analysis. Patients with positive FFR (FFR_CT ≤0.80) were less likely to have non-obstructive disease on invasive coronary angiography than patients with negative FFR (FFR_CT >0.80) (20.5% vs. 46.1%, P=0.0001). After FFR_CT, 67.0% of patients with positive results underwent revascularization, whereas 96.1% of patients with negative FFR_CT were medically treated. MACE occurred in 5 patients with positive FFR_CT, but none occurred in patients with negative FFR_CT within 90 days.

Conclusions: In this Japanese population, FFR_CT modified the treatment strategy in more than half of the patients. FFR_CT showed potential for stratifying patients suspected of CAD properly into invasive or non-invasive management pathways.

Physiological assessment is paramount in the management of patients with coronary artery disease (CAD). Invasive fractional flow reserve (FFR) has proven to have excellent diagnostic accuracy and to improve the clinical outcome.^1–3 As a result, the international guidelines strongly endorse invasive FFR in the management of CAD patients.⁴ However, the adoption of FFR is limited in the real world and its invasive nature is thought to be a major hindrance to its use.⁵

Coronary computed tomography angiography (cCTA)-derived FFR (FFR_CT) has recently evolved as a novel non-invasive physiological assessment.^6–8 It has a strong correlation with invasive FFR and high diagnostic accuracy in terms of identifying flow-limiting coronary stenoses. As well as its diagnostic performance, the clinical utility of FFR_CT has been demonstrated. For instance, FFR_CT significantly modifies the downstream clinical management actions, spares a considerable number of patients from unnecessary invasive coronary angiography (ICA), and improves outcomes following FFR_CT-directed management strategies.^9–11 This clinical utility has been recently corroborated in real-world settings by a large international multicenter prospective study, the Assessing Diagnostic Value of Non-invasive FFR_CT in Coronary Care (ADVANCE) registry.¹²

However, FFR_CT is not yet widely used in clinical settings in Japan because it was not covered by health insurance until December 2018. Thus, because clinical FFR_CT data in Japan are scarce, it remains unknown whether the clinical utility shown in the international studies will directly apply to the Japanese population. Therefore, we conducted this subanalysis of the ADVANCE registry to assess the clinical impact of FFR_CT in Japan.

Methods

The ADVANCE registry is an international, multicenter, prospective registry including 5,083 patients from 38 international sites, of whom 1,758 (35%) enrolled in 13 Japanese institutions were analyzed in this subanalysis. The details of the study protocol and methods have been published previously.^12,13 In brief, stable patients in whom cCTA was clinically indicated and who demonstrated >30% diameter stenosis (DS) were prospectively enrolled based on clinical need. Inclusion criteria were age >18 years, ability to provide informed consent, and CAD on cCTA. Exclusion criteria were poor quality cCTA images, life expectancy <1 year, and an inability to comply with follow-up requirements. All patients provided written informed consent. The study protocol was approved by the ethical committees at each participating site and the study was registered with NCT [NCT02499679] and UMIN [UMIN000032186].

CT Interpretation and Management Strategies

After the acquisition of cCTA images, the site investigators interpreted them part of routine clinical practice. They reported their initial management plans for each patient based on cCTA alone, and then submitted the CT data for FFR_CT analysis (HeartFlow, Redwood City, CA, USA). Vessel segments ≥2 mm in diameter were evaluated for luminal narrowing, and the per-vessel maximum stenosis was categ orized as 0%, 1–29%, 30–49%, 50–70%, 71–90%, >90%, or total occlusion. Within 48 h after data submission, the site investigators received the FFR_CT results and reported their management strategy after taking account of the FFR_CT results. FFR_CT value ≤0.80 was considered physiologically significant, but the actual decision as to treating medically or to revascularize was made at the discretion of the referring physicians.

cCTA and FFR_CT findings were also analyzed in a core laboratory blinded to clinical information, symptom status, and outcomes (Duke Clinical Research Institute (DCRI) [Durham, NC, USA]). The core laboratory reviewed the cCTA findings and defined their independent management plans on the basis of cCTA alone, and then defined a second management plan after the FFR_CT information was provided. This involved adjudication of vessel- and lesion-specific ischemia, measuring the FFR_CT 2 cm distal to focal lesions. Both the site and laboratory management strategies were categorized into the following options: (1) optimal medical therapy (MT), (2) percutaneous coronary intervention (PCI), (3) coronary artery bypass grafting (CABG), or (4) additional diagnostic testing required. The additional diagnostic testing was selected when a further non-invasive ischemic test was thought to be required and was assigned in the core-lab in the setting of a 40–90% stenosis given the need to determine the hemodynamic significance of a lesion to guide ICA, PCI, or CABG referral.

Study Endpoints

The endpoints in the main study were also assessed in this subanalysis. These included the reclassification rate between cCTA-based and cCTA plus FFR_CT-based management plans, incidence of ICA demonstrating absence of obstructive CAD (no coronary stenosis >50% by site interpretation), percutaneous and surgical revascularization rates, and 90-day survival free from major adverse cardiovascular events (MACE). MACE was defined as death, myocardial infarction (MI), or acute coronary syndrome (ACS) requiring unplanned hospitalization and urgent revascularization. All events were adjudicated by an independent Clinical Events Committee blinded to cCTA, and FFR_CT information.

Statistical Analysis

Continuous data are presented as mean (±standard deviation) or median (interquartile range, IQR), categorical data as frequency and percentage, as appropriate. Net reclassification was compared by the Mann-Whitney and Kruskal-Wallis tests as appropriate. Differences between anatomic severity and rates of positive FFR_CT were assessed by the unpaired t-test. Univariable and multivariable logistic regression models using step-wise selection were used to estimate the odds of revascularization. Variables showing a P-value <0.10 in the univariable analysis were included into the multivariable model. The fit of the final model was assessed using the Log Likelihood and Akaike Information Criterion. The chi-square test of independence was used to assess if negative catheterization and MI/death were independent of or associated with minimum FFR_CT strata (>0.80/≤0.80); when the expected frequency was ≤5, the Fisher’s exact test was used. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated; in cases of zero frequency cell, relative risk and associated 95% CIs were calculated. A two-sided level of P<0.05 was considered statistically significant.

Results

Baseline Patient Characteristics

Baseline patient demographics are summarized in Table 1. In total, 1,829 patients were enrolled into this study, of whom 1,758 had FFR_CT results available and 71 had cCTA results alone. With regard to the latter, 4 cases were not submitted to FFR_CT analysis, 2 of those were directly sent to ICA based on the lesion severity on cCTA, 1 had multiple coronary stents, 1 for other reason (marked unknown by the site). The remaining 67 (3.7%) subjects were rejected owing to a cCTA image quality not being suitable for FFR_CT analysis (e.g., field of view too wide, incomplete myocardial coverage, slice thickness >1.0 mm, or severe motion and/or blooming artifacts). In terms of the symptoms, angina including typical and atypical was most frequently found (62.3%). The mean Diamond-Forrester pretest probability for obstructive coronary disease was 55.0%. There was no significant difference in demographics between those who received cCTA alone vs. cCTA plus FFR_CT.

Table 1. Demographics, Coronary Artery Disease Risk Factors, and Symptom Status

	CTA only (n=71)	FFRCT (n=1,758)	Total (n=1,829)
Age (years)	71.4±10.9	69.3±10.0	69.4±10.0
Male sex	46 (64.8%)	1,150 (65.4%)	1,196 (65.4%)
Hypertension	35 (49.3%)	1,066 (60.6%)	1,101 (60.2%)
Diabetes mellitus	36 (50.7%)	559 (31.8%)	595 (32.5%)
Hyperlipidemia	35 (49.3%)	1,066 (60.6%)	1,101 (60.2%)
Smoking history
Current smoker	8 (11.3%)	312 (17.7%)	320 (17.5%)
Ex-smoker	28 (39.4%)	585 (33.3%)	613 (33.5%)
Never smoked	30 (42.3%)	727 (41.4%)	757 (41.4%)
Unknown	5 (7.0%)	134 (7.6%)	139 (7.6%)
Angina status
Atypical	18 (25.4%)	628 (35.7%)	646 (35.3%)
Typical	20 (28.2%)	473 (26.9%)	493 (27.0%)
Dyspnea	3 (4.2%)	50 (2.7%)	53 (2.9%)
Non-cardiac pain	0 (0%)	48 (2.7%)	48 (2.6%)
None	30 (42.3%)	548 (31.2%)	578 (31.6%)
Unknown	0 (0%)	11 (0.6%)	11 (0.6%)
CCS Angina Class
Grade I	8 (40.0%)	56 (33.0%)	164 (33.3%)
Grade II	9 (45.0%)	240 (50.7%)	249 (50.5%)
Grade III	3 (15.0%)	60 (12.7%)	63 (12.8%)
Grade IV	0 (0%)	12 (2.5%)	12 (2.4%)
Unknown	0 (0%)	5 (1.1%)	5 (1.0%)
cCTA rejection rate	67 (94.4%)	1 (0.1%)	68 (3.7%)
Diamond-Forester risk	54.9±23.1	55.0±20.4	55.0±20.5

Values are reported as mean±SD and number (percentage). CCS, Canadian Cardiovascular Society; CTA, computed tomography angiography; FFR_CT, coronary CTA-derived fractional flow reserve.

Extent and Severity of CAD by cCTA and FFR_CT

cCTA revealed coronary DS ≥50% in 77.9% of subjects (n=1,369) and >70% DS in 46.9% (n=824), and demonstrated 2- or 3-vessel disease (≥50% DS) in 20.8% and 12.9%, respectively. An ischemia-generating lesion defined as FFR_CT ≤0.80 was present in at least 1 coronary territory in 71.0% (n=1,249) of patients. As shown in Figure 1, LAD had more frequently anatomically severe (>70% DS) coronary disease (33.8%) and physiologically significant (FFR_CT ≤0.80) lesions (n=1,131, 65.4%) compared with the other 2 coronary arteries: left circumflex (LCX) had 15.6% (>70% DS) and positive FFR_CT (n=456, 26.4%), (P<0.001), and right coronary artery (RCA) had 18.1% (>70% DS) and positive FFR_CT (n=422, 24.4%), (P<0.001). Overall, the LAD demonstrated significantly lower median FFR_CT values (0.77: IQR - 0.68 - 0.84) compared with the LCX (0.88: IQR - 0.81 - 0.93) and RCA (0.87: IQR - 0.80 - 0.91), (P<0.001). In the moderate (30–70%) stenosis, the proportion of physiologically significant stenosis (FFR_CT ≤0.80) was significantly higher in the LAD (59.0%) compared with LCX (31.8%) and RCA (28.6%), (P<0.001).

Figure 1.

Distribution of positive or negative FFR_CT according to the cCTA-derived anatomical degree of coronary artery stenosis in each coronary artery territory. (A) Left anterior descending artery (LAD), (B) left circumflex (LCX), and (C) right coronary artery (RCA). cCTA, coronary computed tomography angiography; FFR_CT, cCTA-derived fractional flow reserve.

Clinical Management Strategies Following FFR_CT

The classification changes in clinical management strategies before and after FFR_CT are summarized in Figure 2. Overall, treatment recommendations were modified after FFR_CT in 865 (55.8%) patients according to site-based plan, and in 987 (56.9%) patients according to core laboratory analysis. Interestingly, when a lesion of interest, which was defined as a vessel with the highest degree of %DS on cCTA, was located in LAD, the treatment strategy was more often modified after FFR_CT than when in non-LAD (LAD, 71.5%; LCX, 65.4%; and RCA, 62.4%; P=0.0272) in the site-based plans.

Figure 2.

Reclassification of management strategies (on site or at the core laboratory) pre- and post-FFR_CT, and actual management at 90 days. CABG, coronary artery bypass grafting; ICA, invasive coronary angiography; PCI, percutaneous coronary intervention. Other abbreviations as in Figure 1.

In the site-based plans, among 797 (45.3%) patients in whom additional testing was thought to be required at the initial evaluation by cCTA alone, FFR_CT reclassified 466 (58.5%) patients to MT, 229 (28.7%) to PCI, 20 (2.5%) to CABG; 110 subjects did not have any post-FFR_CT determination entered by the site. Of 389 (22.1%) patients who were assigned to MT by the initial cCTA, 349 (89.7%) remained as MT, 20 (5.1%) patients were reclassified to PCI, and 1 (0.3%) patient to CABG. Among 467 patients in whom revascularization (PCI: n=440, CABG: n=27) was indicated by the initial cCTA, 107 (22.9%) were reclassified to MT (PCI to MT: n=102, 23.2%, CABG to MT: n=5, 18.5%) Of note, most patients (n=946, 96.1%) in whom MT was indicated after FFR_CT had MT as their actual treatment, and 444 (67%) patients indicated for revascularization actually underwent revascularization (Figure 3). In addition, the lower the FFR_CT values, the more patients were revascularized (Figure 4).

Figure 3.

Actual treatment at 90 days between revascularization and medical therapy on site determined post-FFR_CT management plan. Abbreviations as in Figures 1,2.

Figure 4.

Actual treatment at 90 days stratified by FFR_CT values. Abbreviations as in Figures 1,2.

Rate of Invasive Angiography and Revascularization After FFR_CT Evaluation

After FFR_CT, 115 of 509 (22.6%) patients with negative FFR_CT and 771 of 1,249 (61.7%) with positive FFR_CT received ICA, and anatomically defined ‘non-obstructive’ disease at ICA (no stenosis >50% at ICA) was markedly less frequent in patients with FFR_CT ≤0.80 (20.5%) than in those with FFR_CT >0.80 (46.1%), (OR 3.29, CI 2.19–4.95, P<0.0001). Invasive FFR adjudication was performed in 78 of 509 (15.3%) patients with negative FFR_CT and 557 of 1,249 (44.6%) with positive FFR_CT (P<0.0001). More patients underwent revascularization among those who had FFR_CT ≤0.80 (67%) compared with FFR_CT >0.80 (3.9%) (Figure 3).

When stratified by 0.05 categorical FFR_CT increments, as the FFR_CT values were lower, more patients received ICA and underwent revascularization (Figure 4). Multivariable analysis demonstrated that diabetes, hyperlipidemia, typical angina symptom, stenosis of >70%DS/occluded vessel, and FFR_CT ≤0.80 were significant predictors of revascularization (Table 2).

Table 2. Multivariable Logistic Regression Analysis of Univariate Predictors of Revascularization Among Subjects With FFR_CT Performed: Full Model

Covariate	Estimates of effect	Odds ratio	P value
Age (≥65 years)	−0.2378	0.79 (0.58–1.07)	0.1261
Female sex	−0.3258	0.72 (0.51–1.02)	0.0619
Diabetes mellitus	0.3394	1.40 (1.06–1.86)	0.0185
Smoking history
Current smoker, or recently quit	0.1081	1.11 (0.75–1.65)	0.5903
Former smoker	−0.9382	0.96 (0.68–1.36)	0.8283
Hyperlipidemia	0.6086	1.17 (0.82–1.67)	<0.0001
Hypertension	0.0485	1.33 (0.58–3.05)	0.3740
Symptom status
Typical angina	1.3336	1.17 (0.82–1.67)	<0.0001
Atypical angina	0.1603	1.33 (0.58–3.05)	0.3740
Dyspnea	0.2823	1.44 (0.63–3.30)	0.5057
Non-cardiac pain	0.3679	3.79 (2.72–5.30)	0.3831
Coronary stenosis >70%	1.8091	6.10 (4.54–8.21)	<0.0001
FFRCT ≤0.80	2.1952	8.98 (5.24–15.38)	<0.0001

Intercept parameter estimate: −4.6565, P<0.0001. Reference categories for covariates: (1) age <65 years, (2) male sex, (3) no diabetes mellitus, (4) never smoked, (5) no hyperlipidemia, (6) no hypertension, (7) no symptom, (8) coronary stenosis: ≤70%, and (9) FFR_CT >0.8. Abbreviations as in Table 1.

MACE

No MACE occurred within 90 days in subjects with FFR_CT >0.80 (n=509). On the other hand, 5 (0.4%, P=0.15) MACE occurred in subjects with FFR_CT ≤0.80 in at least 1 coronary artery (n=1,249). The MACE included 2 urgent unplanned hospitalizations for ACS and urgent revascularization, and 3 deaths.

Discussion

The main findings of this study are: (1) FFR_CT modified the treatment strategy in more than 50% of patients in Japan; (2) actual treatment closely followed FFR_CT recommendations with 96.1% in whom MT was recommended receiving MT and 67% in whom revascularization was recommended receiving revascularization within 90 days; (3) patients with positive FFR_CT who underwent ICA were unlikely to reveal non-obstructive disease; and (4) positive FFR_CT was a strong predictor of subsequent revascularization.

Impact of FFR_CT on Treatment Strategy Modification

cCTA offers excellent performance for detection of CAD.^14,15 However, not all anatomic stenoses detected by cCTA are physiologically important or relevant to symptoms or clinical events.^9,16,17 Discordance between anatomy and physiology is not uncommon and when discordance is present, a physiology-guided approach has been shown to lead to better clinical outcomes than anatomy-guided management.^2,3,18,19 Given the superiority of a physiology-guided approach, it is not surprising that substantial strategy modifications were made based on FFR_CT analysis and cCTA findings when compared with the management plan based on cCTA alone. Similar strategy modification has been also reported for invasive angiography and FFR.^20–22 However, it should be noted that not all cases indicated for revascularization either in the core-lab or site investigations underwent revascularization. This means that although FFR_CT ≤0.80 was considered physiologically significant and as an indication for revascularization, actual treatment decisions were made by referring physicians after taking account of other factors such as lesion locations (proximal or distal), morphologies (focal or diffuse), or vessel sizes etc. as well as FFR_CT. In fact, only two-thirds of the patients to whom revascularization was recommended after FFR_CT actually underwent coronary revascularization. The actual treatment decision might have been also affected by symptom status, patient age, and different practice patterns across facilities even in the same country. It should be borne in mind that although FFR_CT gives valuable information for decision-making of treatment strategy, it is just one piece of clinical information that physicians need to take into consideration.

FFR_CT Reduced Additional Testing and Stratified Patients

Evaluation of chest pain by cCTA has proven to be safe and clinically effective.^23,24 However, the problem when using cCTA as the first-line assessment is that it may increase invasive cardiac catheterizations and subsequent coronary revascularizations, many of which may not have clinical benefit if there is no physiological significance. In this context, additional non-invasive functional testing (e.g., nuclear myocardial perfusion imaging) may help select patients for further invasive procedures. However, such functional testing in addition to cCTA can be inaccurate (false negative or false positive), costly, and requires an additional hospital/clinic visit as well as more radiation exposure.^25–27 FFR_CT may provide advantages in each of these areas, because of its accuracy^6–8 and elimination of additional visits and radiation exposure. Our analysis demonstrated that the proportion of patients deemed to require additional testing in Japan, at nearly 45% following the initial assessment by cCTA, was reduced to nearly zero (0.02%) after FFR_CT analysis.

Downstream Clinical Decision-Making in Japan Following FFR_CT

In this broad early clinical experience with FFR_CT in Japan, patients with positive FFR_CT were much more likely to have obstructive CAD on ICA and to undergo revascularization than patients with a negative FFR_CT result. These findings were consistent with the broader cohort examined in the ADVANCE registry and highlighted the early clinical adoption of FFR_CT across sites participating in the registry, including Japan. When FFR_CT was negative, patients were less likely to have obstructive CAD, and the vast majority was medically treated and had safe outcomes through 90 days. These findings indicated that FFR_CT can be used to assign invasive procedures to those who truly benefit from them.

MACE After FFR_CT

In terms of the clinical outcomes, no MACE were reported within 90 days in patients with negative FFR_CT, whereas MACE did occur in those who had positive FFR_CT. As the event rate was limited, even in patients with positive FFR_CT, the difference was not statistically significant in this subanalysis. However, very similar findings were reported with statistical significance in the full cohort of this registry.¹² These observations indicated that patients with positive FFR_CT are at higher risk of MACE compared with those with negative FFR_CT, which is clinically relevant because patients with negative FFR_CT can be safely deferred from not only revascularization but also invasive catheterization, considering that most of them were medically treated in the end. The ability of FFR_CT to differentiate patients who require further invasive diagnostic testing and possible intervention from those who do not need them has also been reported in another cohort.¹⁰

FFR_CT as a Continuous Variable

In clinical trials, invasive FFR is usually used in a dichotomous fashion; for example, ≤0.80 is for revascularization and >0.80 is for medical treatment, and it is often the case in clinical settings as well (Figure 5).^2,3,17 Recently, however, it has been recognized that FFR is not such a black-and-white index but a continuous variable such that those patients with the lowest values have the worst prognosis and the largest benefit from revascularization.^28,29 Our data suggested that FFR_CT is similar, with subjects with lower FFR_CT values being more likely to undergo revascularization. These findings are clinically important because it might be possible to estimate future events and stratify the patients for risk and referral to invasive angiography according to the degree of reduction in the FFR_CT value. FFR_CT has the potential to be used not only for decision-making about invasive procedures but also for optimization of medical treatment.

Figure 5.

Cumulative events curves within 90 days between patients with positive (≤0.80) and negative (>0.80) FFR_CT. (A) Major adverse cardiac events (all-cause mortality, myocardial infarction, unplanned hospitalization leading to urgent revascularization), and (B) all-cause mortality and myocardial infarction alone. Abbreviations as in Figure 1.

Discordance Between Anatomy and Function on Coronary CT

For intermediate lesions, FFR_CT was more likely to be positive in the LAD than in the non-LAD (RCA or LCX) vessels. Moreover, in mild or almost normal-looking vessels (%DS: 0–50%), the proportion of positive FFR_CT was higher in the LAD than in the non-LAD. On the other hand, in more severe stenoses (%DS >70%) negative FFR_CT was more frequent in non-LAD compared with the LAD. These discordances between anatomy and physiology are well known as a visual-functional mismatch on invasive angiography and FFR.²⁶ The findings also demonstrated that such discordance is present for cCTA and FFR_CT as well, which further confirms the importance of functional assessment in non-invasive testing. If lesions are assessed solely anatomically, they are likely to be underdiagnosed in the LAD and overdiagnosed in the remaining vascular territories from a physiological perspective (Figure 1). It has been reported that age, lesion location, plaque morphology, and vessel size contribute to the mismatch on invasive angiography and FFR.³⁰ Further studies are necessary to investigate the factors that are associated with the discordance between cCTA and FFR_CT.

Potential of FFR_CT in Japan

This study suggests that FFR_CT can be used in the same way in Japan as in other Western countries because the patients in this Japanese subanalysis showed almost comparable demographics, pretest probability, and cCTA acceptance rate, and then demonstrated similar clinical outcomes as in the whole cohort.¹⁴ cCTA is widely available and being used as the first-line non-invasive assessment for many patients across Japan. Therefore, it is presumed that many patients suspected of having CAD are undergoing cCTA, subsequent ICA, and eventually revascularization. Our findings highlighted the potential of FFR_CT to help facilitate combined anatomical and physiological decision-making to more appropriately guide medical management and ICA referral. The very high acceptance rate of cCTA for FFR_CT analysis in Japan (96.3%) confirms the robustness of FFR_CT and its clinical feasibility in practice in Japan. Importantly, these decisions are enabled without the need for additional testing or radiation exposure. The combination of these factors suggests that FFR_CT will facilitate a more physiology-orientated approach in Japan.

Study Limitations

Firstly, because this was a subanalysis with a smaller sample size than the full global study cohort, clinical outcomes between patients with positive and negative FFR_CT were not statistically significant. However, similar findings reaching statistical significance have been reported in the full cohort.¹² Also this is only the first 90-day results, and longer-term follow-up at 1 and 3 years is underway. Secondly, this is a prospective registry and considered reflective of a real-world situation, but selection bias cannot be totally excluded. Lastly, because a certain number of patients underwent invasive FFR adjudication, their actual treatment strategies might have been based not only on FFR_CT but also invasive FFR.

Conclusions

This subanalysis of the Japanese population in the global international FFR_CT ADVANCE registry showed that FFR_CT considerably modified treatment strategy and that positive FFR_CT was associated with higher rates of ICA showing obstructive CAD and subsequent coronary revascularization. Importantly, a negative FFR_CT result was managed with MT in nearly all subjects and was associated with excellent outcomes through 90 days.

Funding

This study was supported by HeartFlow, Inc., Redwood City, CA, USA, via individual Clinical Study Agreements with each enrolling institution and with the Duke Clinical Research Institute (DCRI) for Core Laboratory activities and Clinical Event Committee adjudication of adverse events.

Any Potential Conflicts of Interest

B.L.N. has received institutional research grants from Siemens and HeartFlow. C.R. is an employee of and has equity in HeartFlow. G.L.R. has received institutional research grant from HeartFlow. J.L. is an advisor to and holds stock options in HeartFlow and Circle CVI. L.M.H.K. has received grant funding to department from Siemens Healthineers, HeartFlow and Verily and Mallinckrodt. N.T. declares consulting fees from Abbott Vascular Japan Co., Ltd. (St. Jude Medical Japan Co., Ltd.), Boston Scientific Japan and receiving lecture fees from Daiichi-Sankyo Co., Ltd. Y.S has received speaking fees from Philips and Abbott Vascular.

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