Instantaneous Wave-free Ratio Research Articles

Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease.

Placebo-controlled evidence from ORBITA-2 found that percutaneous cutaneous intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many. The reason for this was unclear. ; This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, non-invasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI. Pre-randomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the Rose angina questionnaire. Disease severity was assessed using quantitative coronary angiography (QCA), stress echocardiography, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR). Bayesian ordinal regression was used. At pre-randomization, the median number of daily angina episodes was 0.8 (0.4-1.6), 64% had Rose angina, QCA diameter stenosis 61 (49-74), stress echocardiography score 1.0 (0.0-2.7), FFR 0.63 (0.49-0.75), and iFR 0.78 (0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with QCA ordinal correlation coefficient 0.06 (95% CrI 0.00 to 0.08); stress echocardiography 0.09 (95% CrI 0.02 to 0.10); FFR 0.04 (95% CrI -0.03 to 0.07); and iFR 0.04 (95% CrI -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR 1.9, 95% CrI 1.6 to 2.1, Pr(Interaction)=99.9% and OR 1.8, 95% CrI 1.6 to 2.1, Pr(Interaction)=99.9%, respectively). Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI.

Assessment Of Coronary Stenoses For Percutaneous Coronary Intervention: A Systematic Review And Network Meta-Analysis Of Randomized Trials

Evidence regarding the comparative efficacy of the different modalities to determine the significance of coronary stenoses in the catheterization laboratory is lacking. We aimed to compare all available modalities guiding the decision to perform percutaneous coronary intervention (PCI). We searched Medline, Embase, and CENTRAL until October 5, 2023. We included trials that randomized patients with greater than 30% stenoses undergoing potential PCI and reported major adverse cardiovascular events (MACE). We performed a frequentist random-effects network meta-analysis and assessed the certainty of evidence using the GRADE approach. We included 15 trials with 16,333 participants with a mean weighted follow-up of 34 months. The trials contained a median of 49.3% (IQR 32.6%, 100%) acute coronary syndrome (ACS) participants. Quantitative flow ratio (QFR) was associated with a decreased risk of MACE compared to coronary angiography (CA) (Risk ratio (RR) 0.68, 95% Confidence Interval (CI) 0.56, 0.82; high certainty), fractional flow reserve (FFR) (RR 0.73, 95%CI 0.58, 0.92; moderate certainty), and instantaneous wave-free ratio (iFR) (RR 0.63, 95%CI 0.49, 0.82; moderate certainty), and ranked first for MACE (88.1% probability of being the best). FFR (RR 0.93; 95%CI 0.82, 1.06; moderate certainty) and iFR (RR 1.07, 95%CI 0.90, 1.28; moderate certainty) likely did not decrease the risk of MACE compared to CA. Intravascular imaging (IVI) may not be associated with a significant decrease in MACE compared to CA (RR 0.85; 95%CI 0.62, 1.17; low certainty) when used to guide the decision to perform PCI. In conclusion, a decision to perform PCI based on QFR was associated with a decreased risk of MACE compared to CA, FFR and iFR in a mixed stable coronary disease and ACS population. These hypothesis-generating findings should be validated in large, randomized, head-to-head trials.

N-of-1 Trial of Angina Verification Before Percutaneous Coronary Intervention.

In stable coronary artery disease, 30% to 60% of patients remain symptomatic despite successful revascularization. Perhaps not all symptoms reported by a patient with myocardial ischemia are, in fact, angina. This study sought to determine whether independent symptom verification using a placebo-controlled ischemic stimulus could distinguish which patients achieve greatest symptom relief from percutaneous coronary intervention (PCI). ORBITA-STAR was a multicenter, n-of-1, placebo-controlled study in patients undergoing single-vessel PCI for stable symptoms. Participants underwent 4 episodes (60 seconds each) of low-pressure balloon occlusion across their coronary stenosis, randomly paired with 4 episodes of placebo inflation. Following each episode, patients reported the similarity of the induced symptom in comparison with their usual symptom. The similarity score ranged from-10 (placebo replicated the symptom more than balloon occlusion) to+10 (balloon occlusion exactly replicated the symptom). The primary endpoint was the ability of the similarity score to predict symptom relief with PCI. Fifty-one patients were recruited, aged 62.9 ± 8.6 years. The median fractional flow reserve was 0.68 (Q1-Q3: 0.57-0.79), and the instantaneous wave-free ratio was 0.80 (Q1-Q3: 0.48-0.89). The median similarity score was 3 (Q1-Q3: 0.875-5.25). The similarity score was a strong predictor of symptom improvement following PCI: a patient with an upper quartile similarity score of 5.25 was significantly more likely to have lower angina frequency at follow-up (OR: 8.01; 95%credible interval: 2.39-15.86) than a patient with a lower quartile similarity score of 0.875 (OR: 1.31; 95%credible interval: 0.71-1.99), Pr(difference) >99.9%. Similarity score powerfully predicted symptom improvement from PCI. These data lay the foundation for independent symptom mapping to target PCI to those patients most likely to benefit. (Systematic Trial of AnginaAssessment Before Revascularization [ORBITA-STAR]; NCT04280575).

Physiological Assessment with iFR prior to FFR Measurement in Left Main Disease.

Despite guideline-based recommendation of the interchangeable use of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) to guide revascularization decision-making, iFR/FFR could demonstrate different physiological or clinical outcomes in some specific patient or lesion subsets. Therefore, we sought to investigate the impact of difference between iFR and FFR-guided revascularization decision-making on clinical outcomes in patients with left main disease (LMD). In this international multicenter registry of LMD with physiological interrogation, we identified 275 patients in whom physiological assessment was performed with both iFR/FFR. Major adverse cardiovascular event (MACE) was defined as a composite of death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The receiver-operating characteristic analysis was performed for both iFR/FFR to predict MACE in respective patients in whom revascularization was deferred and performed. In 153 patients of revascularization deferral, MACE occurred in 17.0% patients. The optimal cut-off values of iFR and FFR to predict MACE were 0.88 (specificity:0.74; sensitivity:0.65) and 0.76 (specificity:0.81; sensitivity:0.46), respectively. The area under the curve (AUC) was significantly higher for iFR than FFR (0.74; 95%CI 0.62-0.85 vs. 0.62; 95%CI 0.48-0.75; p = 0.012). In 122 patients of coronary revascularization, MACE occurred in 13.1% patients. The optimal cut-off values of iFR and FFR were 0.92 (specificity:0.93; sensitivity:0.25) and 0.81 (specificity:0.047; sensitivity:1.00), respectively. The AUCs were not significantly different between iFR and FFR (0.57; 95%CI 0.40-0.73 vs. 0.46; 95%CI 0.31-0.61; p = 0.43). While neither baseline iFR nor FFR was predictive of MACE in patients in whom revascularization was performed, iFR-guided deferral seemed to be safer than FFR-guided deferral.

Evaluation of Instantaneous Wave-Free Ratio and Fractional Flow Reserve in Severe Aortic Valve Stenosis.

The optimal functional evaluation of coronary artery stenosis in patients with severe aortic stenosis (AS) has not been established. The objective of the study was to evaluate the instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with and without severe AS. We retrospectively investigated 395 lesions in 293 patients with severe AS and 2257 lesions in 1882 patients without severe AS between 2010 and 2022 from a subgroup of the Interventional Cardiology Research In-Cooperation Society FFR Registry. All patients had FFR values, and iFR was analyzed post hoc using dedicated software only in lesions with adequate resting pressure curves (311 lesions in patients with severe AS and 2257 lesions in patients with nonsevere AS). The incidence of iFR ≤0.89 was 66.6% and 31.8% (P<0.001), while the incidence of FFR ≤0.80 was 45.3% and 43.9% (P=0.60) in the severe AS group and the nonsevere AS group, respectively. In the severe AS group, most lesions (95.2%) with iFR >0.89 had FFR >0.80, while 36.2% of lesions with iFR ≤0.89 had FFR >0.80. During a median follow-up of 2 years, FFR ≤0.80 was significantly associated with deferred lesion failure (adjusted hazard ratio, 2.71 [95% CI, 1.08-6.80]; P=0.034), while iFR ≤0.89 showed no prognostic value (adjusted hazard ratio, 1.31 [95% CI, 0.47-3.60]; P=0.60) in the severe AS group. Lesions with iFR ≤0.89 and FFR >0.80, in particular, were not associated with a higher rate of deferred lesion failure at 3 years compared with lesions with iFR >0.89 (15.4% versus 17.0%; P=0.58). This study suggested that FFR appears to be less affected by the presence of severe AS and is more associated with prognosis. iFR may overestimate the functional severity of coronary artery disease without prognostic significance, yet it can be useful for excluding significant stenosis in patients with severe AS.

Diagnostic Accuracy of Pre-Transcatheter Aortic Valve Replacement Nitroglycerin-Free Fractional Flow Reserve-Computed Tomography-Based Physiological Assessment in Patients With Severe Aortic Stenosis for Predicting Post-Transcatheter Aortic Valve Replacement Ischemia.

Fractional flow reserve-computed tomography (FFRCT) has not been validated in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) for coronary artery disease due to theoretical difficulties in using nitroglycerin for such patients.Methods and Results: In this single-center study, we prospectively enrolled 21 patients (34 vessels) and performed pre-TAVR FFRCTwithout nitroglycerin, pre-TAVR invasive instantaneous wave-free ratio (iFR) measurements, and post-TAVR FFR measurements using a pressure wire. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pre-TAVR FFRCT≤0.80 to predict post-TAVR invasive FFR ≤0.80 were 82%, 83%, 82%, 71%, and 90%, respectively. A receiver operating characteristic analysis demonstrated an optimal cutoff of 0.78 for pre-TAVR FFRCTto indicate post-TAVR FFR ≤0.80, with an area under the curve (AUC) of 0.84, and the counterpart cutoff of pre-TAVR iFR was 0.89 with an AUC of 0.86. FFRCTwithout nitroglycerin could be a useful non-invasive imaging modality for assessing the severity of coronary artery lesions in patients with severe AS.

The Value of a Coronary Computed Tomography Angiography plus Stress Cardiac Magnetic Resonance Imaging Strategy for the Evaluation of Patients with Chronic Coronary Syndrome.

Background: Noninvasive imaging methods, either anatomical or functional tests, serve as essential instruments for the appropriate management of patients with established or suspected coronary artery disease (CAD). We sought to evaluate the safety and efficacy of a coronary computed tomography angiography (CCTA) plus stress cardiac magnetic resonance imaging (S-CMR) strategy in patients with chronic coronary syndrome (CCS). Methods: Patients with suspected CCS showing intermediate coronary plaques (stenosis 30-70%) at CCTA underwent S-CMR. Patients with a positive S-CMR were referred to invasive coronary angiography (ICA) plus instantaneous wave-free ratio (iFR), and myocardial revascularization if recommended. All patients received guideline-directed medical therapy (GDMT), including high-dose statins, regardless of myocardial revascularization. The primary endpoint was a composite of death from cardiovascular causes, non-fatal myocardial infarction, and unplanned revascularization. Results: According to the results of CCTA, 62 patients showing intermediate coronary plaques underwent S-CMR, which was positive for a myocardial perfusion deficit in n = 17 (27%) and negative in n = 45 (73%) patients. According to the results of ICA plus iFR, revascularization was performed in 13 patients. No differences in the primary endpoint between the positive and negative S-CMR groups were observed at 1 year (1 [5.9%] vs. 1 [2.2%], p = 0.485) and after a median of 33.4 months (2 [11.8%] vs. 3 [6.7%]; p = 0.605). Conclusions: Our study suggests that a CCTA plus S-CMR strategy is effective for the evaluation of patients with suspicion of CCS at low-intermediate risk, and it may help to refine the selection of patients with intermediate coronary plaques at CCTA needing coronary revascularization.

Fractional flow reserve and instantaneous wave-free ratio in coronary artery bypass grafting: a meta-analysis and practice review.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive methods to assess the functional significance of intermediate severity coronary lesions. Both indexes have been extensively validated in clinical trials in guiding revascularisation in patients with stable ischaemic heart disease undergoing percutaneous coronary intervention (PCI) with improved clinical outcomes. However, the role of these tools in coronary artery bypass grafting (CABG) is less clear. A meta-analysis of randomised trials and observational studies was carried out to help in determining the optimal strategy for assessing lesion severity and selecting graft targets in patients undergoing CABG. Electronic searches were carried out on Embase, MEDLINE, and Web of Science. A group of four authors independently screened and then assessed the retrieved records. Cochrane's Risk of Bias and Robins-I tools were used for bias assessment. A survey was conducted among surgeons and cardiologists to describe current attitudes towards the preoperative use of functional coronary investigations in practice. Clinical outcomes including mortality at 30 days, perioperative myocardial infarction, number of grafts, incidence of stroke, rate of further need for revascularisation, and patient-reported quality of life did not differ in CABG guided by functional testing from those guided by traditional angiography.The survey revealed that in half of the surgical and cardiology units functional assessment is performed in CABG patients; there is a general perception that functional testing has improved patient care and its use would clarify the role of moderate coronary lesions that often need multidisciplinary rediscussions; moderate stenosis are felt to be clinically relevant; and anatomical considerations need to be taken into account together with functional assessment. At present, the evidence to support the routine use of functional testing in intermediate lesions for planning CABG is currently insufficient. The pooled data currently available do not show an increased risk in mortality, myocardial injury, and stroke in the FFR/iFR-guided group. Further trials with highly selected populations are needed to clarify the best strategy. ClinicalTrials.gov, identifier (CRD42023414604).

Coronary physiology instantaneous wave-free ratio (iFR) derived from x-ray angiography using artificial intelligence deep learning models: a pilot study.

Coronary angiography (CAG)-derived physiology methods have been developed in an attempt to simplify and increase the usage of coronary physiology, based mostly on dynamic fluid computational algorithms. We aimed to develop a different approach based on artificial intelligence methods, which has seldom been explored. Consecutive patients undergoing invasive instantaneous free-wave ratio (iFR) measurements were included. We developed artificial intelligence (AI) models capable of classifying target lesions as positive (iFR ≤ 0.89) or negative (iFR > 0.89). The predictions were then compared to the true measurements. Two hundred-fifty measurements were included, and 3 models were developed. Model 3 had the best overall performance: accuracy, negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity were 69%, 88%, 44%, 74%, and 67%, respectively. Performance differed per target vessel. For the left anterior descending artery (LAD), model 3 had the highest accuracy (66%), while model 2 the highest NPV (86%) and sensitivity (91%). PPV was always low/modest. Model 1 had the highest specificity (68%). For the right coronary artery, model 1's accuracy was 86%, NPV was 97%, and specificity was 87%, but all models had low PPV (maximum 25%) and low/modest sensitivity (maximum 60%). For the circumflex, model 1 performed best: accuracy, NPV, PPV, sensitivity, and specificity were 69%, 96%, 24%, 80%, and 68%, respectively. We developed 3 AI models capable of binary iFR estimation from CAG images. Despite modest accuracy, the consistently high NPV is of potential clinical significance, as it would enable avoiding further invasive maneuvers after CAG. This pivotal study offers proof of concept for further development.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min−1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Hemodynamic Insights into Combined Fractional Flow Reserve and Instantaneous Wave-Free Ratio Assessment Through Quantitative [15O]H2O PET Myocardial Perfusion Imaging.

In patients evaluated for obstructive coronary artery disease (CAD), guidelines recommend using either fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) to guide coronary revascularization decision-making. The hemodynamic significance of lesions with discordant FFR and iFR measurements is debated. This study compared [15O]H2O PET-derived absolute myocardial perfusion between vessels with concordant and discordant FFR and iFR measurements. Methods: We included 197 patients suspected of obstructive CAD who had undergone [15O]H2O PET perfusion imaging and combined FFR/iFR interrogation in 468 vessels. Resting myocardial blood flow (MBF), hyperemic MBF, and coronary flow reserve (CFR) were compared among 4 groups: FFR low/iFR low (n = 79), FFR high/iFR low (n = 22), FFR low/iFR high (n = 22), and FFR high/iFR high (n = 345). Predefined [15O]H2O PET thresholds for ischemia were 2.3 mL·min-1·g-1 or less for hyperemic MBF and 2.5 or less for CFR. Results: Hyperemic MBF was lower in the concordant low (2.09 ± 0.67 mL·min-1·g-1), FFR high/iFR low (2.41 ± 0.80 mL·min-1·g-1), and FFR low/iFR high (2.40 ± 0.69 mL·min-1·g-1) groups compared with the concordant high group (2.91 ± 0.84 mL·min-1·g-1) (P < 0.001, P = 0.004, and P < 0.001, respectively). A lower CFR was observed in the concordant low (2.37 ± 0.76) and FFR high/iFR low (2.64 ± 0.84) groups compared with the concordant high group (3.35 ± 1.07, P < 0.01 for both). However, for vessels with either low FFR or low iFR, quantitative hyperemic MBF and CFR values exceeded the ischemic threshold in 38% and 49%, respectively. In addition, resting MBF exhibited a negative correlation with iFR (P < 0.001) and was associated with FFR low/iFR high discordance compared with concordant low FFR/low iFR measurements, independent of clinical and angiographic characteristics, as well as hyperemic MBF (odds ratio [OR], 0.41; 95% CI, 0.26-0.65; P < 0.001). Conclusion: We found reduced myocardial perfusion in vessels with concordant low and discordant FFR/iFR measurements. However, FFR/iFR combinations often inaccurately classified vessels as either ischemic or nonischemic when compared with hyperemic MBF and CFR. Furthermore, a lower resting MBF was associated with a higher iFR and the occurrence of FFR low/iFR high discordance. Our study showed that although combined FFR/iFR assessment can be useful to estimate the hemodynamic significance of coronary lesions, these pressure-derived indices provide a limited approximation of [15O]H2O PET-derived quantitative myocardial perfusion as the physiologic standard of CAD severity.

Сравнительная характеристика больных с ишемической болезнью сердца и стенозирующим атеросклерозом коронарных артерий в зависимости от показателей моментального резерва кровотока

The paper presents a comparative analysis of 56 patients suffering from stable ischemic heart disease and coronary artery stenosis in the range of 65–90% depending on the instantaneous wave-free ratio (iFR). Two groups of 28 patients took part in the research. The index iFR was less than 0,80 in the first group, whereas it was more than 0,94 in the second. It reveals that the indexes of the pre-test probability of coronary artery disease (CAD) did not significantly differ among the groups of patients irrespective of the different iFR values. Patients with low iFR indexes (the first group) tend to have diabetes mellitus as the result of overweight, predominant systolic hypertension, diastolic myocardial dysfunction, atherogenic dyslipidemia, and visible signs of renal dysfunction. According to the exercise ECG Stress test results, the patients of the first group were more frequently diagnosed with symptoms of the myocardial ischemia and its electrical instability in the form of high gradations of ventricular extrasystole. The paper outlines that the previously described factors increase the probability of low iFR with the same initial pre-test probability of CAD, so they can be used as indicators of the advisability of performing endovascular interventions in patients with chronic coronary syndrome.

Virtual stenting and coregistration of instantaneous wave-free ratio to predict the physiological effect of percutaneous coronary intervention in patients with multilevel coronary artery disease

Aim. To evaluate the accuracy of virtual stenting in predicting the physiological effect of percutaneous coronary intervention (PCI) for multilevel coronary artery disease (CAD).Material and methods. In order to define PCI strategy, 34 patients with multilevel CAD underwent assessment of instantaneous wave-free ratio (iFR) with mapping. Using the virtual stenting, predicted iFR (priFR) was assessed. After stent implantation, the factual iFR (fiFR) was re-assessed. A discrepancy between the priFR and fiFR by 0,03 was considered the threshold level of a significant difference and "poor agreement" criterion between measurements.Results. Mean iFR before PCI was 0,77±0,11; after PCI, this indicator increased significantly and amounted to 0,94±0,04 (p&lt;0,001). Comparison of the predicted and factual iFR revealed that the difference did not significantly depend on the value (rxy=-0,183; p=0,300), and mean difference between measurements was 0,013 (standard deviation, ±0,019), which indicates no systematic discrepancy and good comparability of the studied methods. In addition, correlation analysis of priFR and fiFR revealed a significant strong (Chaddock scale) direct relationship (r=0,854; p&lt;0,001). Independent predictors of "poor agreement" were heart rate and systolic blood pressure before surgery. Discrepancy in decisions on the choice of stented lesions and the required number of stents based on coronary angiography (CAG) and MRI occurred in 21 patients (62%) and 16 patients (47%), respectively. After iFR measurement, there was a significant decrease in the mean length of affected segment (from 61,82±19,68 mm (CAG) and 49,15±19,19 mm (iFR)), which made it possible to significantly reduce the number of implanted stents from 1,91±0,57 (CAG) to 1,50±0,56 (p=0,001).Conclusion. Mapping the iFR and virtual stenting technology makes it possible to revise the classification of coronary lesions by length, which leads to a significant reduction in the number of implanted stents and the length of stented segment. High correlation between priFR and fiFR achieved in our study indicates the high accuracy of virtual stenting in predicting the physiological effect of stenting.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW

ObjectivesThe objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). Background15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. MethodsThe RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies.Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan.The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. ConclusionsThe RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. Clinical trial registration informationClinical-Trials.gov (#NCT05134012).

Reproducibility of instantaneous wave-free ratio and angiography coregistration in patients with coronary heart disease and diffuse and multilevel coronary artery lesion

Aim. To determine the reproducibility of the results of instantaneous wavefree ratio (iFR) and angiography coregistration in patients with coronary heart disease (CAD) with multilevel and diffuse lesions of the coronary arteries.Materials and methods. The study included 34 patients with chronic ischemic heart disease (CAD) with diffuse and/or multilevel coronary stenoses &gt;50%. In 41 coronary arteries, two consecutive iFR pullback of the conductor were performed and paired iFR angio-coregistrations were formed, reflecting changes in iFR gradients (Δ iFR) along the entire length of the studied artery. To compare the results of paired studies, the following values were used: 1) indices of distal iFR; 2) maximum Δ iFR; 3) Δ iFR of all stenoses ˃50%.Results. Comparable values of distal iFR were obtained 0,84 [0,78; 0,89] vs. 0,85 [0,77; 0,88]) with an average difference of the first and second measurements of 0,001, maximum ΔiFR (0,08 [0,05; 0,14] vs. 0,08 [0,05; 0,13]) with a mean difference of -0,004 and ΔiFR of all stenoses &gt;50% (0,05 [0,02; 0,11] vs. 0,05 [ 0,02; 0,10]) with an average difference of -0.001. Lin’s concordance correlation coefficient and Intraclass Correlation Coefficients calculated for the three parameters studied showed a good level of agreement (0,97; 0,98; 0,98) with excellent reliability (0,97; 0,98; 0,97).Conclusion. In patients with multilevel and diffuse lesions of the coronary artery, iFR angio-coregistration has a fairly high reproducibility.

Revascularization and Mortality at 5 Years After Treatment Guided By Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Revascularization and Mortality at 5 Years After Treatment Guided By Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina

BackgroundPercutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina.ResultsA total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group.ConclusionsAmong patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.)

Validation of the resting full-cycle ratio and diastolic pressure ratio through myocardial perfusion imaging with [15O]H2O positron emission tomography

Abstract Background Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging techniques and clinical trials. However, new invasive pressure indices that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. Purpose To validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. Methods A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of myocardial perfusion, and within 2 weeks coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. In the case of RFR and dPR, values ≤ 0.89, and for FFR, values ≤ 0.8 were classified as abnormal. PET myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) served as reference standards. The index tests and gold standard results were evaluated by blinded researchers. Results Figure 1 shows the diagnostic performance of each ratio in coronary arteries with stenoses (136 of 320 vessels, 38%). The overall diagnostic accuracies of RFR, dPR and FFR did not differ when PET MBF &amp;lt; 2.3 ml · min-1 and PET MPR &amp;lt; 2.5 were considered as the reference standard. No significant differences were observed in the areas under the receiver-operating-characteristic (ROC) curve among the indices (Figure 2). In addition, the indices demonstrated comparable performance when the analysis included all of the vessels. Conclusion The novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance that is comparable to FFR when using [15O]H2O PET to assess myocardial perfusion abnormalities. These findings suggest that RFR and dPR may be considered for clinical use in symptomatic patients with CAD.Figure 1Diagnostic performance;StenosisFigure 2ROC curve analysis;Stenosis

Diagnostic accuracy of vessel fractional flow reserve compared to conventional diagnostic tools in patients with coronary artery stenosis

Abstract Background Wire-based fractional flow reserve (FFR) is currently the golden standard in a physiological assessment for intermediate coronary artery stenosis (CAS). However, the clinical advantage of FFR has been limited by its invasiveness. In the previous study with a small number of participants (334 patients), three-dimensional quantitative coronary angiography (3D-QCA)-based vessel FFR (vFFR) has shown non-inferiority to wire-based FFR in diagnostic accuracy. There has been no reports regarding the relationship between vFFR and other conventional physiological assessment tools. Methods The present study was a retrospective registry designed to evaluate the diagnostic accuracy of vFFR compared to the conventional reference standard (wire-based FFR ≤0.80). Between January 2019 and February 2022, patients with stable or unstable angina, and non-ST-elevation acute coronary syndrome who had undergone physiological assessments [wire-based FFR, instantaneous wave-free ratio (iFR), resting full-cycle ratio (RFR), and/or coronary computed tomography angiography-derived FFR (FFRCT)] before percutaneous coronary intervention were included for the present analysis. The exclusion criteria were ST-elevation myocardial infarction, previous coronary artery bypass grafting, cardiogenic shock, and adenosine intolerance. In the present study, we investigate the relationship between vFFR and conventional tools such as wire-based FFR, iFR, RFR, and/or FFRCT in patients with intermediate CAS, including multi-vessel disease, severe coronary calcium, in-stent restenosis, and hemodialysis. Results The study included 722 patients (mean age, 70±10 years; male, 80%) who underwent vFFR in 698 patients (97%), wire-based FFR in 711 (98%), iFR in 523 (72%), RFR in 109 (15%), and FFRCT in 48 (7%). Most patients presented stable angina (93%). In the present study, multi-vessel disease was identified only 20% of all. A total of 1108 target vessels were LAD in 549 (50%), LCx in 287 (26%), and RCA in 272 (24%), respectively. Bifurcation lesions and in-stent restenosis were present in 12% and 13%, respectively. The subjects were diagnosed several comorbidities, such as hypertension (77%), dyslipidemia (57%), diabetes mellitus (40%), and hemodialysis (12%). Overall, vFFR showed good correlations with wire-based FFR (r=0.70; p&amp;lt;0.001), IFR (r=0.57; p&amp;lt;0.001), and RFR (r=0.69; p&amp;lt;0.001). However, the correlation between vFFR and FFRCT was weak (r=0.36; p&amp;lt;0.001). Furthermore, vFFR had a good diagnostic accuracy (sensitivity, specificity, negative predictive value and positive predictive value; 81%, 88%, 82% and 87%, respectively) to identify the lesions with wire-based FFR≤0.80 (AUC, 0.87; 95% CI, 0.84-0.90; p&amp;lt;0.001). Conclusion In this large number cohort, the 3D-QCA based vFFR has a good correlation with wire-based FFR, and a high diagnostic accuracy to detect the lesion with FFR ≤ 0.80 even in patients with severe coronary calcification, in-stent restenosis, and hemodialysis.Scatter plotsBland-Altman plots

Abstract 12127: Diagnostic Performance of Fractional Flow Reserve, Instantaneous Wave-Free Ratio and Quantitative Flow Ratio, on the Same Patient and Procedure

Introduction: Contemporary percutaneous coronary intervention (PCI) seeks precision and physiological assessment of coronary artery stenosis. Fractional Flow Reserve (FFR) is currently the gold standard for lesion physiology assessment; however, it's invasive and expensive. Other modalities, such as Quantitative Flow Ratio (QFR) and Instantaneous Wave-Free Ratio (iFR), can also determine the functional repercussion of coronary stenosis less invasively. Hypothesis: The results of FFR, iFR, and QFR of the same lesion, obtained during the same PCI, demonstrate the significant diagnostic capability of iFR and QFR, compared with FFR. Methods: Retrospective and unicentric study with stable chronic heart disease patients who underwent PCI. For every angiographic lesion, FFR, iFR and QFR were realized during the PCI. QFR was performed by an X-ray technician, blinded to the FFR and iFR results. A descriptive analysis was performed, as well as a correlation between the three measurements with Pearson’s r, chi-square, and ROC curve; and Bland-Altman plot for the results of FFR and QFR. Results: Thirty-six lesions of 27 patients were analyzed. For FFR, stenosis was considered significant when the result was &lt;0.80, obtaining 17 lesions (52%) as significant; for iFR, it was &lt;0.89, obtaining 14 significant lesions (38%); and for QFR, it was &lt;0.85, resulting in 19 (52%) significant lesions. Considering that FFR is the actual gold standard, a ROC curve was used to analyze QFR, were the best cutoff value was 0.88 with a sensitivity of 88% and specificity of 64% (AUC of 0.86, 95% CI 0.736- 0.991, p&lt;0.001), while for iFR the best cutoff value was 0.90 with a sensitivity of 82% and specificity of 74% (AUC of 0.85, 95% CI 0.722-0.984, p&lt;0.001). Pearson’s r revealed a significant correlation between FFR-iFR (r=0.6, p&lt;0.001), FFR-QFR (r=0.58, p&lt;0.001), and QFR-iFR (r=0.62, p&lt;0.001). Bland-Altman plot showed no significant difference between the data obtained with FFR and QFR. Chi-square test determined (p&lt;0.001) that the three angiographic methods had a good correlation in determining whether a lesion was significant. Conclusion: The study demonstrated the significant diagnostic capability that the QFR and iFR methods have, when compared against the current gold standard FFR.