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Background: Our understanding of human coronary physiological behaviour is derived from animal models. We sought to describe physiological behaviour across a large collection of invasive pressure and flow velocity measurements, to provide a better understanding of the relationships between these physiological parameters and to evaluate the rationale for resting stenosis assessment. Methods and results: Five hundred and sixty-seven simultaneous intracoronary pressure and flow velocity assessments from 301 patients were analysed for coronary flow velocity, trans-stenotic pressure gradient (TG), and microvascular resistance (MVR). Measurements were made during baseline and hyperaemic conditions. The whole cardiac cycle and the diastolic wave-free period were assessed. Stenoses were assessed according to fractional flow reserve (FFR) and quantitative coronary angiography DS%. With progressive worsening of stenoses, from unobstructed angiographic normal vessels to those with FFR ≤ 0.50, hyperaemic flow falls significantly from 45 to 19 cm/s, Ptrend < 0.001 in a curvilinear pattern. Resting flow was unaffected by stenosis severity and was consistent across all strata of stenosis (Ptrend > 0.05 for all). Trans-stenotic pressure gradient rose with stenosis severity for both rest and hyperaemic measures (Ptrend < 0.001 for both). Microvascular resistance declines with stenosis severity under resting conditions (Ptrend < 0.001), but was unchanged at hyperaemia (2.3 ± 1.1 mmHg/cm/s; Ptrend = 0.19). Conclusions: With progressive stenosis severity, TG rises. However, while hyperaemic flow falls significantly, resting coronary flow is maintained by compensatory reduction of MVR, demonstrating coronary auto-regulation. These data support the translation of coronary physiological concepts derived from animals to patients with coronary artery disease and furthermore, suggest that resting pressure indices can be used to detect the haemodynamic significance of coronary artery stenoses. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to define which measure of microvascular best predicts the extent of left ventricular (LV) infarction. Background Microvascular injury after ST-segment elevation myocardial infarction (STEMI) is an important determinant of outcome. Several invasive measures of the microcirculation at primary percutaneous coronary intervention (PPCI) have been described. One such measure is zero-flow pressure (Pzf), the calculated pressure at which coronary flow would cease. Methods In 34 STEMI patients, Pzf, hyperemic microvascular resistance (hMR), and index of microcirculatory resistance (IMR) were derived using thermodilution flow/pressure and Doppler flow/pressure wire assessment of the infarct-related artery following PPCI. The extent of infarction was determined by blinded late gadolinium enhancement on cardiac magnetic resonance at 6 months post-PPCI. Infarction of ≥24% total LV mass was used as a categorical cutoff in receiver-operating characteristic curve analysis. Results Pzf was superior to both hMR and IMR for predicting ≥24% infarction area under the curve: 0.94 for Pzf versus 0.74 for hMR (p = 0.04) and 0.54 for IMR (p = 0.003). Pzf ≥42 mm Hg was the optimal cutoff value, offering 100% sensitivity and 73% specificity. Patients with Pzf ≥42 mm Hg also had a lower salvage index (61.3 ± 8.1 vs. 44.4 ± 16.8, p = 0.006) and 6-month ejection fraction (62.4 ± 3.6 vs. 49.9 ± 9.6, p = 0.002). In addition, there were significant direct relationships between Pzf and troponin area under the curve (rho = 0.55, p = 0.002), final infarct mass (rho = 0.75, p < 0.0001), percentage of LV infarction and percent transmurality of infarction (rho = 0.77 and 0.74, respectively, p < 0.0001), and inverse relationships with myocardial salvage index (rho = −0.53, p = 0.01) and 6-month ejection fraction (rho = −0.73, p = 0.0001). Conclusions Pzf measured at the time of PPCI is a better predictor of the extent of myocardial infarction than hMR or IMR. Pzf may provide important prognostic information at the time of PPCI and merits further investigation in clinical studies with relevant outcome measures. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to perform hemodynamic mapping of the entire vessel using motorized pullback of a pressure guidewire with continuous instantaneous wave-free ratio (iFR) measurement. Background Serial stenoses or diffuse vessel narrowing hamper pressure wire–guided management of coronary stenoses. Characterization of functional relevance of individual stenoses or narrowed segments constitutes an unmet need in ischemia-driven percutaneous revascularization. Methods The study was performed in 32 coronary arteries with tandem and/or diffusely diseased vessels. An automated iFR physiological map, integrating pullback speed and physiological information, was built using dedicated software to calculate physiological stenosis severity, length, and intensity (ΔiFR/mm). This map was used to predict the best-case post–percutaneous coronary intervention (PCI) iFR (iFR exp ) according to the stented location, and this was compared with the observed iFR post-PCI (iFR obs ). Results After successful PCI, the mean difference between iFR exp and iFR obs was small (mean difference: 0.016 ± 0.004) with a strong relationship between ΔiFR exp and ΔiFR obs (r = 0.97, p < 0.001). By identifying differing iFR intensities, it was possible to identify functional stenosis length and quantify the contribution of each individual stenosis or narrowed segment to overall vessel stenotic burden. Physiological lesion length was shorter than anatomic length (12.6 ± 1.5 vs. 23.3 ± 1.3, p < 0.001), and targeting regions with the highest iFR intensity predicted significant improvement post-PCI (r = 0.86, p < 0.001). Conclusions iFR measurements during continuous resting pressure wire pullback provide a physiological map of the entire coronary vessel. Before a PCI, the iFR pullback can predict the hemodynamic consequences of stenting specific stenoses and thereby may facilitate the intervention and stenting strategy. [ABSTRACT FROM AUTHOR]

This commentary refers to 'Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis', by M.A. Kelshiker I et al i . https://doi.org/10.1093/eurheartj/ehab775 and the discussion piece 'An attempt to better show some results such as the comparison of mortality and major adverse cardiovascular events between the abnormal and normal coronary flow reserve cohorts', by H. Zhu I et al i . https://doi.org/10.1093/eurheartj/ehac166. Here are the correct figures: our event-rate analysis identified 28 studies with published event rates for MACE and 13 studies with published event rates for mortality. [Extracted from the article]

Objectives: To evaluate the first experience of real-time instantaneous wave-free ratio (iFR) measurement by clinicians.Background: The iFR is a new vasodilator-free index of coronary stenosis severity, calculated as a trans-lesion pressure ratio during a specific period of baseline diastole, when distal resistance is lowest and stable. Because all previous studies have calculated iFR offline, the feasibility of real-time iFR measurement has never been assessed.Methods: Three hundred ninety-two stenoses with angiographically intermediate stenoses were included in this multicenter international analysis. Instantaneous wave-free ratio and fractional flow reserve (FFR) were performed in real time on commercially available consoles. The classification agreement of coronary stenoses between iFR and FFR was calculated.Results: Instantaneous wave-free ratio and FFR maintain a close level of diagnostic agreement when both are measured by clinicians in real time (for a clinical 0.80 FFR cutoff: area under the receiver operating characteristic curve [ROC(AUC)] 0.87, classification match 80%, and optimal iFR cutoff 0.90; for a ischemic 0.75 FFR cutoff: iFR ROC(AUC) 0.90, classification match 88%, and optimal iFR cutoff 0.85; if the FFR 0.75-0.80 gray zone is accounted for: ROC(AUC) 0.93, classification match 92%). When iFR and FFR are evaluated together in a hybrid decision-making strategy, 61% of the population is spared from vasodilator while maintaining a 94% overall agreement with FFR lesion classification.Conclusion: When measured in real time, iFR maintains the close relationship to FFR reported in offline studies. These findings confirm the feasibility and reliability of real-time iFR calculation by clinicians. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the instantaneous wave-free ratio (iFR) can detect improvement in stenosis significance after percutaneous coronary intervention (PCI) and compare this with fractional flow reserve (FFR) and whole cycle Pd/Pa. Design: A prospective observational study was undertaken in elective patients scheduled for PCI with FFR ≤0.80. Intracoronary pressures were measured at rest and during adenosine-mediated vasodilatation, before and after PCI. iFR, Pd/Pa and FFR values were calculated using the validated fully automated algorithms. Setting: Coronary catheter laboratories in two UK centres and one in the USA. Patients: 120 coronary stenoses in 112 patients were assessed. The mean age was 63±10 years, while 84% were male; 39% smokers; 33% with diabetes. Mean diameter stenosis was 68±16% by quantitative coronary angiography. Results: Pre-PCI, mean FFR was 0.66±0.14, mean iFR was 0.75±0.21 and mean Pd/Pa 0.83±0.16. PCI increased all indices significantly (FFR 0.89±0.07, p<0.001; iFR 0.94±0.05, p<0.001; Pd/Pa 0.96±0.04, p<0.001). The change in iFR after intervention (0.20 ±0.21) was similar to ?FFR 0.22±0.15 (p=0.25). ?FFR and ?iFR were significantly larger than resting ?Pd/Pa (0.13±0.16, both p<0.001). Similar incremental changes occurred in patients with a higher prevalence of risk factors for microcirculatory disease such as diabetes and hypertension. Conclusions: iFR and FFR detect the changes in coronary haemodynamics elicited by PCI. FFR and iFR have a significantly larger dynamic range than resting Pd/Pa. iFR might be used to objectively document improvement in coronary haemodynamics following PCI in a similar manner to FFR. [ABSTRACT FROM AUTHOR]

Abstract: Background: The role of resting pressure parameters, i.e. instantaneous wave-free ratio (iFR), and resting distal coronary pressure/aortic pressure (Pd/Pa) in assessing functionally significant stenosis remains controversial. We sought to assess the diagnostic performance of iFR and resting whole-cycle Pd/Pa in Asian patients. Methods: In this study, 238 consecutive lesions (no total occlusions) in which fractional flow reserve (FFR) was measured with both intravenous and intracoronary adenosine administration were included. Coded resting pressure data were sent to the core laboratory in which iFR was calculated in a blinded fashion. Results: FFR and iFR had unimodal distributions and the correlation was r =0.77 (95% confidence interval, 0.71 to 0.82). In a receiver-operating-characteristic curve analysis, iFR had an area under the curve (AUC) of 0.9 at FFR≤0.80. The best cut-off value for iFR was 0.90 with a sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 76%, 86%, 82% and 80%, and 82%, respectively. The resting whole-cycle Pd/Pa cut-off of 0.91 demonstrated a diagnostic accuracy of 82% (AUC 0.9). However, iFR had higher discriminatory power than the resting whole-cycle Pd/Pa. Conclusion: Both iFR and resting whole-cycle Pd/Pa showed good diagnostic performance to define the functionally significant stenosis in an independent Asian cohort distributed unimodally and without total occlusions. However, further validation is needed to explore the areas of disagreement between different physiologic parameters prior to adoption of resting pressure parameters into routine clinical practice. [Copyright &y& Elsevier]

Current in vivo models of arterial lesions often lead to unpredictable results in terms of lesion anatomy and hemodynamical significance. This study aimed to evaluate the impact of coronary stenosis using a novel in vivo adjustable stenosis model capable of mimicking advanced human coronary lesions. We developed a series of balloon expandable covered coronary stents with a central restriction, mimicking different intermediate to severe stenosis, and implanted them percutaneously in coronary arteries of eight healthy hybrid Landrace pigs. Optical coherence tomography (OCT) pullbacks and fractional flow reserve (FFR) were acquired along the artery after implantation of the stenotic stents for precise evaluation of anatomy and functional impact. Diameter and area stenosis after deployment of the stenosis implant were, on average, respectively, 54.1 ± 5.9 and 78.4 ± 5.8 % and average FFR value was 0.83 (SD 0.13). There was a low correlation between FFR and MLA evaluated by OCT ( r = 0.02, p = 0.94), improved with percentage area stenosis ( r = −0.55, p = 0.12), or OCT volumetric evaluation of the stenosis taking into account not only the MLA but also the length of the lesion ( r = −0.78, p = 0.01). This study presents a method and proof of concept for percutaneously introducing, and removing, anatomical stenosis of predetermined severity in vivo. Such in vivo model may be used to create and evaluate the impact of focal stenoses on physiological parameters such as FFR. [ABSTRACT FROM AUTHOR]

Objectives This study sought to evaluate the effects of fractional flow reserve (FFR) measurement variability on FFR-guided treatment strategy. Background Current appropriateness guidelines recommend the utilization of FFR to guide coronary revascularization based on a fixed cut-off of 0.8. This rigid approach does not take into account the intrinsic biological variability of a single FFR result and the clinical judgment of experienced interventionists. Methods FFR reproducibility data from the landmark Deferral Versus Performance of PTCA in Patients Without Documented Ischemia (DEFER) trial was analyzed (two repeated FFR measurements in the same lesion, 10 min apart) and the standard deviation of the difference (SDD) between repeated measurements was calculated. The measurement certainty (probability that the FFR-guided revascularization strategy will not change if the test is repeated 10 min later) was subsequently established across the whole range of FFR values, from 0.2 to 1. Results Outside the [0.75 to 0.85] FFR range, measurement certainty of a single FFR result is >95%. However, closer to its cut-off, certainty falls to less than 80% within 0.77 to 0.83, reaching a nadir of 50% around 0.8. In clinical practice, that means that each time a single FFR value falls between 0.75 and 0.85, there is a chance that the FFR-derived revascularization recommendation will change if the measurement is repeated 10 min later, with this chance increasing the closer the FFR result is to 0.8. Conclusions A measurement FFR gray-zone is found between 0.75 and 0.85]. Therefore, clinicians should make revascularization decisions based on broadened clinical judgment when a single FFR result falls within this uncertainty zone, particularly between 0.77 and 0.83, when measurement certainty falls to less than 80%. [ABSTRACT FROM AUTHOR]

Aims: We studied the prevalence of hyponatraemia and its prognostic implications in a large population of adult patients with congenital heart disease (ACHD). [ABSTRACT FROM PUBLISHER]

Supplemental Digital Content is available in the text. Background: Specific algorithms for use of optical coherence tomography (OCT) to guide percutaneous coronary intervention (PCI) are scarce. Also, the relative benefits of intravascular imaging guidance have not been tested against an optimized angiography-guided PCI strategy. In iSIGHT (Optical Coherence Tomography Versus Intravascular Ultrasound and Angiography to Guide Percutaneous Coronary Interventions), we aimed to investigate whether OCT-guided PCI achieves noninferior stent expansion compared with intravascular ultrasound (IVUS) guidance and if both imaging modalities lead to superior stent expansion compared with an optimized angiography-based strategy. Methods: Patients ≥18 years old undergoing PCI for ≥1 lesion in native coronaries of 2.25 to 4.00 mm in diameter were randomized 1:1:1 to OCT-, IVUS-, or angiography-guided PCI. Predetermined guidance protocols were applied in all groups. An external elastic membrane–based protocol was used for stent sizing by OCT and IVUS. The primary end point was noninferiority of stent expansion (minimum stent area ≥90% of the average reference lumen area), measured by post-PCI OCT, in OCT-guided versus IVUS-guided PCI (noninferiority margin, 6.5%). Results: One hundred fifty-one patients (156 lesions) were randomly allocated to OCT (51 lesions [32.7%]), IVUS (52 lesions [33.3%]), or angiography (53 lesions [34.0%]). Stent expansion with OCT guidance (98.01±16.14%) was noninferior to IVUS (91.69±15.75%; 1-sided lower 95% CI, 0.55 mm2; P non-inferiority<0.001) and superior to angiography (90.53±14.84%, P =0.041). IVUS and angiography obtained similar stent expansions (P =0.921). Stent edge dissection and periprocedural complication rates were not significantly different among the groups. Conclusions: Stent expansion with OCT guidance using a dedicated external elastic membrane–based sizing strategy was noninferior to that achieved with IVUS and superior to an optimized angiographic strategy. Registration: URL: plataformabrasil.saude.gov.br; Unique identifier: 69968417.8.0000.5462. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR. Methods: We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg. Results: We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P <0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P <0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: −0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively. Conclusions: The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment. [ABSTRACT FROM AUTHOR]

Background: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation. Methods: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2). Results: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s−1 versus post-TAVI 3.04±1.6 mm Hg·cm·s−1 [ P =0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [ P =0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74. Conclusions: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease. [ABSTRACT FROM AUTHOR]

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 Angina Assessment Before Revascularization [ORBITA-STAR]; NCT04280575) [Display omitted] [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree on the hemodynamic significance of a coronary lesion in ≈20% of cases. It is unknown whether the physiological pattern of disease is an influencing factor for this. This study assessed whether the physiological pattern of coronary artery disease influences discordance between FFR and iFR measurement. Methods and Results: Three-hundred and sixty intermediate coronary lesions (345 patients; mean age, 64.4±10.3 years; 76% men) with combined FFR, iFR, and iFR pressure-wire pullback were included for analysis from an international multicenter registry. Cut points for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89, respectively. Lesions were classified into FFR+/iFR+ (n=154; 42.7%), FFR−/iFR+ (n=38; 10.6%), FFR+/iFR− (n=41; 11.4%), and FFR−/iFR− (n=127; 35.3%) groups. The physiological pattern of disease was classified according to the iFR pullback recordings as predominantly physiologically focal (n=171; 47.5%) or predominantly physiologically diffuse (n=189; 52.5%). Median FFR and iFR were 0.80 (interquartile range, 0.75–0.85) and 0.89 (interquartile range, 0.86–0.92), respectively. FFR disagreed with iFR in 22% (79 of 360). The physiological pattern of disease was the only influencing factor relating to FFR/iFR discordance: predominantly physiologically focal was significantly associated with FFR+/iFR− (58.5% [24 of 41]), and predominantly physiologically diffuse was significantly associated with FFR−/iFR+ (81.6% [31 of 38]; P <0.001 for pattern of disease between FFR+/iFR− and FFR−/iFR+ groups). Conclusions: The physiological pattern of coronary artery disease was an important influencing factor for FFR/iFR discordance. [ABSTRACT FROM AUTHOR]

The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov , NCT04892537 , and completed. Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77–1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI –0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation. [ABSTRACT FROM AUTHOR]

Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease. • The angiograms of the 200 participants randomised in the ORBITA trial were visually assessed, twice, by 25 cardiologists • The cardiologists predicted the FFR and iFR visually, just using the angiogram • The visual FFR and iFR provided significant additional information in predicting placebo-controlled ischaemia improvement with stenting • In this analysis, expert group consensus visual assessment provided as much additional information as invasively measured FFR and iFR [ABSTRACT FROM AUTHOR]