Coronary microvascular dysfunction (CMD) has been proposed as a major mechanism and a potential therapeutic target for diabetic cardiomyopathy (DbCM); however, it has not been fully investigated in a clinical setting. The angiography-derived index of microcirculatory resistance (AMR) is a novel non-invasive measurement of CMD that exhibits promising clinical applications.

AMR was measured in hospitalized patients with DbCM and in control patients. The incidence, clinical characteristics, risk factors, and effects of pharmacological interventions on CMD were investigated.

AMR was significantly higher in patients who met the DbCM-2B diagnostic criteria. The independent risk factors for abnormal AMR included diabetes, body mass index (BMI), and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Patients with elevated NT-pro-BNP had high AMR, and those grouped by medication indicated that ACEI/ARB, sacubitril/valsartan, and trimetazidine might lower AMR in patients with elevated NT-pro-BNP.

The DbCM-2B diagnostic criteria demonstrated a strong correlation with CMD. ACEI/ARB, sacubitril/valsartan, and trimetazidine might improve CMD in patients with DbCM.

The Tpeak-Tend interval on electrocardiogram may be a predictor of worse outcomes in Takotsubo syndrome (TTS), but the mechanisms have not been fully determined. This study aimed to investigate the relationships between the corrected Tpeak-Tend (cTp-e) interval and coronary microvascular-dysfunction (CMD) assessed by the angiography-derived index of microvascular resistance (Angio-IMR) and the in-hospital prognosis in patients with TTS.

We retrospectively evaluated 111 consecutive patients admitted for TTS who underwent coronary angiography at Kindai University Hospital from October 2009 to July 2023. The Tpeak-Tend interval was defined as the time interval between the peak and the end of the T wave in electrocardiogram lead V5 on admission. Angio-IMR was assessed from aortic pressure, quantitative flow ratio (QFR), vessel length and hyperemic velocity using the formula described in validation studies. QFR, vessel length and hyperemic velocity was derived from coronary angiography and QAngio XA 3D software package. The degree of CMD was assessed by the maximum Angio-IMR value in each of the three coronary arteries. The primary endpoint was the relationship between the grade of a prolonged cTp-e interval on admission and Angio-IMR. The secondary endpoint was the relationship between the grade of a prolonged cTp-e interval on admission and in-hospital adverse cardiovascular events (composite of acute heart failure, cardiogenic shock, life-threatening arrhythmia, thrombotic events, stroke and all-cause death). The median age was 77.5 [71.0-83.0] years, and most patients were women (82.0%). The median cTp-e interval was 114.5 [91.2-147.0] ms. The patients were categorized according to the tertiles of the cTp-e interval (T1: 52.4-96.9 ms; T2: 100.1-129.1 ms; T3: 131.7-309.8 ms). There was a stepwise increment in the values of maximum Angio-IMR in each of the three coronary arteries in tertiles of the cTp-e interval (T1 vs. T2 vs. T3: 16.1 [14.7-19.3] vs. 21.8 [16.0-31.1] vs. 29.0 [27.2-31.9], P < 0.001). In-hospital adverse cardiovascular events occurred in 53 of 111 patients (47.7%). There was a stepwise increment in the incidence of in-hospital adverse cardiovascular events in tertiles of the cTp-e interval (T1 vs. T2 vs. T3: 27.1% vs. 54.1% vs. 62.2%, P = 0.007). The multivariable analysis showed that prolonged cTp-e interval (OR: 1.30; 95% CI: 1.12-1.56; P < 0.001) was independent predictors of in-hospital adverse cardiovascular events.

The Tpeak-Tend interval on admission reflected CMD and predicts in-hospital adverse cardiovascular events in patients with TTS.

Complete revascularization has been shown to be superior to culprit-only treatment in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, it remains unclear whether complete revascularization should be guided by coronary physiology or conventional angiography. Angiography-derived physiology may allow functional assessment and procedural guidance using angiograms from primary percutaneous coronary intervention (PCI), potentially maximizing the benefits of a physiology-guided approach. We present the design of a dedicated study that will address this research gap.

The Functional Coronary Angiography to Indicate and Guide Revascularization in STEMI Patients with Multivessel Disease (AIR-STEMI) trial is a prospective, randomized, international, multicenter, open-label study with blinded adjudicated evaluation of outcomes. After successful treatment of the culprit lesion, patients will be randomized to receive PCI of the nonculprit lesions guided by conventional angiography or by angiography-derived fractional flow reserve (FFR). The primary endpoint is the composite endpoint of all-cause death, any myocardial infarction (MI), any cerebrovascular accident, or any revascularization. It will be censored once the last enrolled patient reaches 1-year follow-up. The secondary endpoint will be the composite of cardiovascular death or MI and each single component of the primary endpoint. All endpoints will be tested also at 3 and 5 years. The sample size for the study is a minimum of 1,800 patients.

The AIR-STEMI trial will provide novel evidence on whether a specific complete revascularization strategy should be applied to patients with STEMI and multivessel disease to improve their clinical outcomes.

ClinicalTrials.gov NCT05818475.

Coronary functional assessment plays a critical role in guiding decisions regarding coronary revascularization. Traditional methods for evaluating functional myocardial ischemia, such as invasive procedures or those involving radiation, have their limitations. Echocardiographic myocardial strain has emerged as a non-invasive and convenient indicator. However, the interpretation of strain values can be subject to inter-operator variability. Artificial intelligence (AI) and machine learning techniques may promise to reduce the variability. By training AI algorithms on a diverse range of echocardiographic data, including strain values, and correlating them with ischemia, it may be possible to develop a robust and automated diagnostic tool. This study aims to provide a non-invasive and effective solution for automated myocardial ischemia detection that can be used in clinical practice. To construct the machine learning model, we used an automatic left ventricular endocardium tracing tool to extract myocardial strain data and integrated it with six clinical features. A coronary angiography-derived fractional flow reserve (caFFR) ≤ 0.80 was defined as the indicator of myocardial ischemia. A total of 636 suspected coronary artery disease subjects were enrolled in this pilot study, where 282 cases (44.3%) had myocardial ischemia. These subjects were randomly divided into training (n = 508) and testing (n = 128) sets at a 4:1. Using ensemble-learning algorithms to train and optimize the model, its diagnostic performance versus caFFR was diagnostic accuracy 85.9%, sensitivity 88.9%, specificity 83.1%, positive predictive value 83.6%, negative predictive value 88.5%. The optimized model achieved an area under the receiver operating characteristic curve (AUC) of 0.915 (95% confidence interval [CI] 0.862-0.968). Our machine learning prototype model based on echocardiographic myocardial strain shows promising results in detecting myocardial ischemia. Further studies are needed to validate its robustness and generalizability on larger patient populations.

The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system.

This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China.

At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained.

In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system.

ClinicalTrials.gov , NCT03656848.

We aim to compare with the diagnostic performance of target-position quantitative flow ratio derived from Murray Law (target-μFR) and vessel quantitative flow ratio derived from Murray Law (vessel-μFR) using the fractional flow reserve (FFR) as reference standard. This study may provide more evidence for the novel clinical usage of target-μFR in the diagnosis of coronary artery disease.

Six hundreds and fifty-six patients (685 lesions) with known or suspected coronary artery disease were screened for this retrospective analysis between January 2021 to March 2023. A total of 161 patients (190 lesions) underwent quantitative coronary angiography and FFR evaluations. In the final analysis, 137 patients (146 lesions) were included in this study. Both of target-μFR and vessel-μFR were compared the diagnostic performance using the FFR ≤ 0.80 as the reference standard.

Both target-μFR (R = 0.84) and vessel-μFR (R = 0.83) demonstrated a strong correlation with FFR, and both methods showed great agreement with FFR. The area under the receiver operating characteristic curve was 0.937 for target-μFR and 0.936 for vessel-μFR in predicting FFR ≤ 0.80. FFR ≤ 0.80 were predicted with high sensitivity (86.44%) and specificity (88.51%) using the pre-defined cutt-off of 0.80 for target-μFR. A good diagnostic performance (sensitivity 92.98% and specificity 91.01%) was also demonstrated by vessel-μFR which the pre-defined cutt-off was 0.80.

The target-μFR has the similar diagnostic performance with vessel-μFR. The accuracy of μFR does not seem to be affected by the selection of the measurement point. Both of the virtual models have been validated as computational tools for diagnosing ischemia and are instrumental in aiding clinical decision-making.

Despite evidence supporting use of fractional flow reserve (FFR) and instantaneous waves-free ratio (iFR) to improve outcome of patients undergoing coronary angiography (CA) and percutaneous coronary intervention, such techniques are still underused in clinical practice due to economic and logistic issues.

We aimed to develop an artificial intelligence (AI)-based application to compute FFR and iFR from plain CA.

Consecutive patients performing FFR or iFR or both were enrolled. A specific multi-task deep network exploiting 2 projections of the coronary of interest from standard CA was appraised. Accuracy of prediction of FFR/iFR of the AI model was the primary endpoint, along with sensitivity and specificity. Prediction was tested both for continuous values and for dichotomous classification (positive/negative) for FFR or iFR. Subgroup analyses were performed for FFR and iFR.A total of 389 patients from 5 centers were enrolled. Mean age was 67.9 ± 9.6 and 39.2% of patients were admitted for acute coronary syndrome. Overall, the accuracy was 87.3% (81.2-93.4%), with a sensitivity of 82.4% (71.9-96.4%) and a specificity of 92.2% (90.4-93.9%). For FFR, accuracy was 84.8% (77.8-91.8%), with a sensitivity of 81.9% (69.4-94.4%) and a specificity of 87.7% (85.5-89.9%), while for iFR accuracy was 90.2% (86.0-94.6%), with a sensitivity of 87.2% (76.6-97.8%) and a specificity of 93.2% (91.7-94.7%, all confidence intervals 95%).

The presented machine-learning based tool showed high accuracy in prediction of wire-based FFR and iFR.

Murray law-based Quantitative Flow Ratio (μQFR) is an innovative AI-driven method for evaluating coronary lesions using contrast flow velocity estimates. Unlike traditional approaches, μQFR does not require pressure wires or hyperemia induction. However, its accuracy compared to Fractional Flow Reserve (FFR) for calcified lesions (ACC/AHA classification B2 or C) remains underexplored.

This study aimed to evaluate the diagnostic accuracy of μQFR in detecting hemodynamically significant calcified coronary stenosis, defined as FFR ≤ 0.80.

In this two-center, investigator-initiated trial, patients with calcified lesions (B2 or C, 30%-90% diameter stenosis) and FFR assessment during coronary angiography were included. μQFR was calculated by a nurse blinded to the FFR results. Sensitivity and specificity of μQFR were compared with FFR as the gold standard.

Among 125 patients, paired μQFR and FFR data were available for 107 patients and 120 lesions. Mean FFR, μQFR, and percent stenosis were 0.775 (95% CI: 0.757-0.793), 0.788 (95% CI: 0.772-0.805), and 56.75% ( ± 10.14%), respectively. μQFR demonstrated a sensitivity of 75% (95% CI: 65.6%-84.6%), a specificity of 77.8% (95% CI: 63.5%-92.0%), a diagnostic precision of 75.8% and an area under the receiver operating characteristic curve of 0.813 (95% CI: 0.714-0.911). The positive predictive value was 88.7%, and the negative predictive value was 57.1%. The positive and negative likelihood ratios were 3.38 and 0.32, respectively.

μQFR is simple to compute and offers moderate diagnostic accuracy for calcified coronary stenosis. It provides a valuable alternative when FFR is unavailable or technically challenging.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are discordant in approximately 20% of cases, and it is unclear whether this is influenced by the physiological pattern of coronary artery disease (CAD). The pull back pressure gradient index (PPGi) can objectively characterize the physiological pattern of CADs.

The aim of this study was to evaluate whether PPGi differed in discordant groups (FFR+/iFR- vs FFR-/iFR+).

The study enrolled 355 patients (390 vessels) with chronic coronary syndrome who had ≥1 epicardial coronary artery lesion with 40% to 90% diameter stenosis by visual assessment on invasive coronary angiography and had analyzable FFR, iFR, and PPGi derived from quantitative flow ratio. Cutoffs for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89. Vessels were classified as FFR+/iFR+ (n = 103 [26.4%]), FFR-/iFR+ (n = 27 [6.9%]), FFR+/iFR- (n = 38 [9.7%]), and FFR-/iFR- (n = 222 [57%]) groups.

Median FFR, iFR, and quantitative flow ratio were 0.84 (Q1-Q3: 0.77-0.90), 0.92 (Q1-Q3: 0.88-0.97), and 0.83 (Q1-Q3: 0.73-0.90), respectively. FFR disagreed with iFR in 16.7% of cases (65 of 390). The median PPGi was 0.75 (Q1-Q3: 0.67-0.85). The physiological pattern of CAD was classified according to the PPGi as predominantly physiologically focal (PPGi ≥0.75) in 209 of 390 vessels (53.6%) or diffuse (PPGi < 0.75) in 181 of 390 vessels (46.4%). The median PPGi was significantly lower in FFR-/iFR+ vs FFR+/iFR- vessels (0.65 [Q1-Q3: 0.60-0.69] vs 0.82 [Q1-Q3: 0.75-0.85]; P < 0.001). Predominantly physiologically focal disease was significantly associated with FFR+/iFR- (76.3% [29 of 38]), while predominantly physiologically diffuse disease was significantly associated with FFR-/iFR+ (96.3% [26 of 27] [P < 0.001] for pattern of CAD between FFR+/iFR- and FFR-/iFR+ groups).

The physiological pattern of CAD is an important influencing factor in FFR/iFR discordance. (Radiographic Imaging Validation and Evaluation for Angio iFR [REVEAL iFR]; NCT03857503).

The coronary angiography-derived fractional flow reserve (FFR) curve, referred to as the Angio-FFR curve, is crucial for guiding percutaneous coronary intervention (PCI). The invasive FFR is the diagnostic gold standard for determining functional significance and is recommended to complement coronary angiography. The invasive FFR curve can quantitatively define disease patterns. The Angio-FFR curve further overcomes the limitation of invasive FFR measurement and thus emerges as a promising approach. However, the Angio-FFR curve computation suffers from a lack of satisfactory trade-off between accuracy and efficiency. In this paper, we propose a bi-variational physics-informed neural operator (BVPINO) for FFR curve assessment from coronary angiography. Our BVPINO combines with the variational mechanism to guide the basis function learning and residual evaluation. Extensive experiments involving coronary angiographies of 215 vessels from 184 subjects demonstrate the optimal balance of BVPINO between effectiveness and efficiency, compared with computational-based models and other machine/deep learning-based models. The results also provide high agreement and correlation between the distal FFR predictions of BVPINO and the invasive FFR measurements. Besides, we discuss the Angio-FFR curve assessment for a novel gradient-based index. A series of case studies demonstrate the effectiveness and superiority of BVPINO for predicting the FFR curve along the coronary artery centerline.

The use of coronary physiology is essential to guide revascularization in patients with stable coronary artery disease. However, some patients without significant angiographic coronary artery disease will experience cardiovascular events at the follow-up. This study aims to determine the prognostic value of the global plaque volume (GPV) in patients with stable coronary artery disease without functionally significant lesions at a 5-year follow-up.

We conducted a multicenter, observational, and retrospective cohort study with a 5-year follow-up. A total of 277 patients without significant coronary artery disease treated with coronary angiography in 2015 due to suspected stable coronary artery disease were included in the study. The 3 coronary territories were assessed using quantitative flow ratio, calculating the GPV by determining the difference between the luminal volume and the vessel theoretical reference volume.

The mean GPV was 170.5 mm3. A total of 116 patients (42.7%) experienced major adverse cardiovascular events (MACE) at the follow-up, including cardiac death (11%), myocardial infarction (2.6%), and unexpected hospital admissions (38.1%). Patients with MACE had a significantly higher GPV (231.6 mm3 vs 111.8 mm3; P < .001). The optimal GPV cut-off point for predicting events was 44 mm3. Furthermore, in the multivariate analysis conducted, plaque volume, diabetes, hypertension, age, dyslipidemia, smoking, age, and GPV > 44 mm3 turned out to be independent predictors of MACE.

GPV, calculated from the three-dimensional reconstruction of the coronary tree, is an independent predictor of events in patients with stable coronary artery disease without significant lesions. A GPV > 44 mm3 is an optimal cut-off point for predicting events.

Refractory angina (RA) is a debilitating condition characterized by persistent angina despite optimized medical therapy and limited options for further revascularization, leading to diminished quality of life and increased healthcare utilization. The RA patient population is rapidly expanding with significant unmet needs. Specialty clinics should be developed to focus on the long-term efficacy and safety of clinically available and novel treatment strategies, emphasizing quality of life.

Patient-focused Comprehensive Angina Relief (CARE) clinics can enhance care and outcomes by providing individualized management for complex RA. This review summarizes peer-reviewed articles from PubMed and trial data from ClinicalTrials.gov. We discuss the epidemiology and pathophysiology of RA, introduce standardized tools for evaluating angina and psychosocial factors, and address symptom management. We also review treatment options such as risk factor modification, medication, and complex revascularization. Additionally, we explore emerging therapies, including coronary sinus occlusion, regenerative therapy, and neuromodulation for 'no-option' RA.

In the next five years, patients with refractory chest pain with or without coronary artery disease will increasingly be referred to specialty clinics for follow-up. Conducting more randomized control clinical trials with larger population subsets will bring novel therapies to the forefront.

The FAVOR III (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease) China trial reported improved clinical outcomes with percutaneous coronary intervention guided by quantitative flow ratio (QFR) compared with angiography. Whether these benefits also apply for patients presenting with "uncertainty-zone" lesions of intermediate physiological significance is uncertain. This study aims to examine the impact of QFR guidance versus angiography guidance on the management and outcomes of percutaneous coronary intervention in uncertainty-zone lesions.

In this prespecified subgroup analysis, offline QFR assessment categorized 873 patients (22.9%) into the uncertainty-zone subgroup, defined as having an offline QFR of 0.75 to 0.85 in all coronary arteries with a lesion causing ≥50% diameter stenosis. At 2 years, the rate of major adverse cardiac events, a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization, occurred in 31 patients (7.0%) in the QFR-guided group and 35 patients (8.3%) in the angiography-guided group (hazard ratio [HR], 0.85 [95% CI, 0.52-1.37]). In landmark analysis, the relative treatment effect of QFR guidance versus angiography guidance on major adverse cardiac events differed before 1 year (4.7% versus 3.8%; HR, 1.25 [95% CI, 0.65-2.40]) and after 1 year (2.3% versus 5.5%; HR, 0.41 [95% CI, 0.20-0.87]) (Pinteraction=0.03), driven by fewer nonprocedural myocardial infarctions and ischemia-driven revascularizations in the QFR-guided group after 1-year follow-up.

In the modest-sized subgroup of patients with physiologically intermediate lesions randomized in the FAVOR III China trial, 2-year clinical outcomes were not significantly improved with a QFR-guided revascularization strategy compared with angiography guidance.

URL: https://www.clinicaltrials.gov; Identifier: NCT03656848.

Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions.

Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization.

A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026).

In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.

The aim of this study was to investigate the relationship between quantitative flow ratio (QFR) after drug-coated balloon (DCB) treatment for in-stent restenosis (ISR) and between neointimal characteristics assessed by optical coherence tomography (OCT) and clinical outcomes. This single-center, retrospective, observational cohort study included ISR patients who underwent DCB angioplasty under OCT guidance. The primary outcome of the study was a target vessel failure (TVF), defined as a composite endpoint of cardiovascular death, target vessel myocardial infarction and target vessel revascularization. During a median follow-up of 756 days (IQR: 443.25, 1134.50), 204 ISR patients underwent OCT-guided DCB angioplasty, resulting in TVF development in 27 patients. At the post-procedural DCB angioplasty, the vessel-level QFR was significantly lower in the TVF group (0.89 [IQR: 0.87, 0.93] vs. 0.93 [IQR: 0.91, 0.96]; P < 0.001) than in the non-TVF group. Analysis of the qualitative characteristics of ISR lesions showed a significantly higher incidence of heterogeneous neointima in the TVF group compared with the non-TVF group (13 [48.15%] vs. 32 [18.08%]; P < 0.001). In the multivariable Cox regression analysis, low vessel-level QFR (HR per 0.1 increase: 0.11; 95% CI: 0.03-0.41; P < 0.001) and heterogeneous neointima were independently associated with TVF. The TVF rate of vessels with the 2 features was 10.69 times higher than that of all other vessels (95%CI [2.05-55.79]; log-rank P < 0.0001). Vessel-level QFR and heterogeneous neointima were independent factors associated with TVF in ISR patients after DCB angioplasty. Adding the QFR measure-ment to OCT findings may enable better discrimination of patients with subsequent TVF post-DCB angioplasty for ISR.

We read the response of Taylor et al [...].

Identification of vulnerable plaques is important for reducing future cardiovascular events. This study aimed to investigate optimal modalities other than intravascular imaging in evaluating vulnerable plaques. We prospectively evaluated 105 non-culprit coronary lesions by CCTA imaging and near-infrared spectroscopy-intravascular ultrasound in 32 patients with acute coronary syndrome. Angiographically-derived ΔQFR and ΔFFRCT were measured as the difference in QFR and FFRCT across the stenosis. A receiver operating characteristic curve analysis was performed to determine the optimal cutoff values of angiographically- and CCTA-derived plaque features for a maxLCBI4mm ≥ 400. The best cutoff values for ΔQFR and ΔFFRCT to predict a maxLCBI4mm ≥ 400 were 0.05 and 0.06, respectively. ΔQFR and ΔFFRCT values and percent diameter stenosis on QCA or CCTA were associated with a maxLCBI4mm ≥ 400 (both P < 0.05). The combination of ΔFFRCT ≥ 0.06 and plaque density predicted a maxLCBI4mm ≥ 400 with 89.4% sensitivity and 84.5% specificity (area under the curve, 0.90; P < 0.0001). There was no significant difference in area under the curve values between ΔQFR and plaque density + ΔFFRCT ≥ 0.06 (0.92 vs. 0.90, P = 0.50). In the diagnosis of vulnerable plaques in acute coronary syndrome, the combination of ΔFFRCT and plaque density shows a diagnostic capability similar to that of ΔQFR in non-culprit lesions.

Angiography-derived fractional flow reserve (FFR) software has been developed using pressure wire based FFR as the reference, however most software requires 2 angiographic views ≥25 degrees apart limiting their clinical utility. This study aims to validate in a prospective multi-center registry the diagnostic performance of a novel angiography derived instantaneous wave-free ratio (Angio-iFR, Royal Philips, Amsterdam) with pressure wire-based iFR as reference.

Coronary angiograms were obtained from patients with coronary artery lesions of between 40% and 90% severity and both iFR and FFR measurements. The pressure wire's position was documented during contrast injection in 2 angiographic views. Angio-iFR/FFR was computed at this exact position by independent corelab analysts blinded to physiological data. The primary end point was the sensitivity and specificity of the Angio-iFR compared to the corresponding invasively measured iFR values. The study was powered to meet prespecified performance goals for sensitivity (75%) and specificity (80%).

A total of 441 patients were enrolled in 32 centers in Europe, Japan, and the United States. Paired Angio-iFR and wire-iFR were available in 398 vessels. The mean iFR was 0.90 (standard deviation: 0.11) with 31.9% of vessels having an iFR≤0.89. Angio-iFR software showed excellent feasibility (97%), and a median analysis time of 55 s. The per-vessel sensitivity and specificity of Angio-iFR was 77% (95% confidence interval [CI]: 69%-84%) and 49% (95% CI: 41%-54%) respectively, which fell below the performance goals.

Angio-iFR did not achieve prespecified diagnostic performance against pressure wire-based iFR. Further software refinements are warranted.

Radiographic Imaging Validation and EvALuation for Angio iFR (ReVEAL iFR), NCT0385750, https://clinicaltrials.gov/study/NCT03857503.

Timely assessment of abnormal microvascular perfusion (MVP) may improve prognosis in patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to determine the clinical implications of contrast-flow quantitative flow ratio (cQFR) in evaluating abnormal MVP and subsequent outcomes among STEMI patients after successful primary percutaneous coronary intervention (PPCI).

The study population consisted of 2 independent cohorts. The diagnostic cohort was used to evaluate the correlation and diagnostic accuracy of cQFR in predicting abnormal MVP. In this cohort, MVP and cQFR of the culprit vessel (n = 186) were assessed from a prospective consecutive registry. Abnormal MVP was determined using myocardial contrast perfusion echocardiography (MCE) in the culprit vessel after PPCI. The prognostic cohort consisted of STEMI patients undergoing PPCI who were followed for a minimum of 2 years (n = 1931). The primary outcome was all-cause mortality.

In the diagnostic cohort, cQFR exhibited a moderate correlation with abnormal MVP assessed by MCE. Specificity, sensitivity, and area under the curve of post-PPCI cQFR to predict abnormal MVP were 81.6 %, 50.9 % and 0.709 (95 % confidence interval: 0.635-0.783), respectively, with the best cut-off value of 0.875. In the prognostic cohort, patients with cQFR <0.875 showed a significantly higher risk of long-term mortality compared to those with cQFR ≥0.875 (median follow-up: 52 months; mortality: 8.0 % vs. 3.8 %; p < 0.001). Cox-regression analysis revealed that cQFR < 0.875 was an independent predictor of long-term mortality (adjusted HR: 2.132; 95 % CI: 1.358-3.346; p = 0.001) after adjusting for age, gender, diabetes mellitus, hyperlipidemia, symptom to balloon time, culprit vessel.

We found that cQFR demonstrated a relatively good performance in predicting abnormal MVP in patients with STEMI after successful PPCI. A cQFR value below 0.875 is an independent predictor of both abnormal MVP and long-term mortality. (Prognostic implication of cQFR in STEMI patients; NCT04996901).

Angiographic microvascular resistance (AMR) serves as an effective metric for assessing coronary microvascular status. The aim of this study was to investigate the predictive value of AMR for left ventricular thrombus (LVT) in ST-segment elevation myocardial infarction. This study enrolled 401 consecutive patients with anterior STEMI who underwent primary percutaneous coronary intervention (PPCI) between May 2019 and July 2023. AMR was measured immediately after PPCI via coronary angiography. LVT was identified during hospitalization through cardiac magnetic resonance imaging (CMR) or transthoracic echocardiography (TTE). Major adverse cardiac and cerebrovascular events (MACCEs) were recorded over 36 months follow-up. The predictive value of AMR was evaluated by logistic regression and receiver operating characteristic (ROC) analysis. Kaplan-Meier analysis was performed to estimate event-free rates for MACCEs. LVT was identified in 38 out of 401 anterior STEMI patients (9.5%). After adjusting for confounders through multivariable analysis, AMR was found to be an independent predictor of LVT (odds ratio [OR] 1.240 per 0.1 mmHg·s/cm, 95% confidence interval [CI]: 1.131-1.359, P < 0.001). ROC analysis demonstrated an area under the curve (AUC) of 0.742. For LVT, AMR provided modest incremental predictive value over established risk factors (continuous net reclassification improvement, 0.826 [95% CI: 0.523-1.129]; P < 0.001). Furthermore, Kaplan-Meier analysis revealed MACCEs for anterior STEMI patients with AMR ≥ 2.82 (log-rank P < 0.001). AMR is an independent predictor of LVT in anterior STEMI, providing incremental predictive value beyond traditional risk factors, and may be utilized to identify patients at risk for LVT.

Previous studies have reported the value of quantitative flow ratio (QFR) to assess the physiological significance of non-culprit lesions (NCLs) in acute myocardial infarction (AMI) patients and of optical coherence tomography (OCT)-defined thin-cap fibroatheroma (TCFA) to identify non-culprit vulnerable plaques.

We sought to systematically compare long-term NCL-related clinical prognosis in an AMI population utilising acute Murray fractal law-based QFR (μQFR) values and OCT-defined TCFA.

Three-vessel OCT imaging and μQFR assessment were conducted in 645 AMI patients, identifying 1,320 intermediate NCLs in non-infarct-related arteries. The primary endpoint was a composite of cardiac death, NCL-related non-fatal myocardial infarction (MI), and NCL-related unplanned coronary revascularisation, with follow-up lasting up to 5 years.

The primary endpoint occurred in 59 patients (11.1%). OCT-defined TCFA independently predicted patient-level (adjusted hazard ratio [HR] 3.05, 95% confidence interval [CI]: 1.80-5.19) and NCL-specific primary endpoints (adjusted HR 4.46, 95% CI: 2.33-8.56). The highest event rate of 29.6% was observed in patients with NCLs that were TCFA (+) with μQFR ≤0.80, compared to 16.3% in those that were also TCFA (+) but with μQFR>0.80, 6.0% in those that were TCFA (-) with μQFR ≤0.80, and 6.6% in those that were TCFA (-) with μQFR>0.80 (log-rank p<0.001). TCFA was an independent predictor for the primary endpoint in ST-segment elevation MI (STEMI; adjusted HR 3.27, 95% CI: 1.67-6.41) and non-STEMI (adjusted HR 3.26, 95% CI: 1.24-8.54) patients, whereas μQFR ≤0.80 was not.

When assessing NCLs during the index procedure in AMI patients, OCT-defined TCFA serves as the dominant prognostic predictor for long-term clinical outcomes, rather than μQFR-determined physiological significance.

Safe deferral of revascularisation is a key aspect of physiology-guided percutaneous coronary intervention (PCI). While recent evidence gathered in the FAVOR III Europe trial showed that quantitative flow ratio (QFR) guidance did not meet non-inferiority to fractional flow reserve (FFR) guidance, it remains unknown if QFR might have a specific value in revascularisation deferral.

We aimed to evaluate the safety of coronary revascularisation deferral based on QFR as compared with FFR.

Patients randomised in the FAVOR III trial in whom PCI was deferred in at least one coronary artery, based on QFR or FFR>0.80, were included in the present substudy. The primary outcome was the 1-year rate of major adverse cardiac events (MACE), with results reported for two subsets of deferred patients: (1) any study lesion deferral and (2) complete study lesion deferral.

A total of 523 patients (55.2%) in the QFR group and 599 patients (65.3%) in the FFR group had at least one coronary revascularisation deferral. Of these, 433 patients (82.8%) and 511 (85.3%) patients, respectively, had complete study lesion deferral. In the "complete study lesion deferral" patient group, the occurrence of MACE was significantly higher in QFR-deferred patients as compared with FFR-deferred patients (24 [5.6%] vs 14 [2.8%], adjusted hazard ratio [HR] 2.07, 95% confidence interval [CI]: 1.07-4.03; p=0.03). In the subgroup of "any study lesion deferral", the MACE rate was 5.6% vs 3.6% (QFR vs FFR), adjusted HR 1.55, 95% CI: 0.88-2.73; p=0.13.

QFR-based deferral of coronary artery revascularisation resulted in a higher incidence of 1-year MACE as compared with FFR-based deferral.

Quantitative flow ratio (QFR) analysis is a simple and non-invasive coronary physiological assessment method with evidence for evaluating stable coronary artery disease with correlation to fractional flow reserve (FFR). However, there is no evidence to recommend its use in non-culprit lesions (NCLs) in myocardial infarction (MI).

We performed a systematic review and meta-analysis using the PRISMA and PROSPERO statements. The study's primary objective was to assess the diagnostic accuracy of QFR in identifying functionally significant NCLs after MI based on invasive FFR and non-hyperemic pressure ratios as references. We obtained values of the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We performed a leave-one-out sensitivity analysis for each study's impact on the overall effect.

We included eight studies, with 713 patients and 920 vessels evaluated with QFR. The overall AUC was 0.941 (I2 = 0.559, p < 0.002), with a sensitivity of 87.3%, a specificity of 89.4%, a PPV of 86.6%, and an NPV of 90.1%. Compared to FFR, we found an AUC of 0.957 (I2 = 0.331, p < 0.194), a sensitivity of 89.6%, a specificity of 89.8%, a PPV of 88.3%, and an NPV of 91%. The sensitivity analysis showed a similar diagnostic performance in both studies.

QFR is effective in analyzing NCLs with a significant diagnostic yield compared to FFR, with an excellent AUC in MI patients. Performing prospective multicenter studies to characterize this population and reproduce our results is essential.

Fractional flow reserve (FFR) derived from coronary angiography, referred to as ICA-FFR, is a less-invasive alternative for invasive FFR measurement based on computational fluid dynamics. Blood flow into side branches influences the accuracy of ICA-FFR. However, properly compensating for side branch flow in ICA-FFR analysis is challenging. In this study, we proposed a physiological side branch flow model to comprehensively compensate side branch flow for ICA-FFR analysis with no need for reconstructing side branch geometry.

the physiological side branch flow model employed a reduced-order model to calculate the pressure distribution in vessel segments. The main coronary artery (without side branches) was delineated and divided based on bifurcation nodes. The model compensates for flow to invisible side branches within each segment and flow to visible side branches at each bifurcation node. Lastly, ICA-FFR based on physiological side branch flow model (ICA-FFR) was calculated from a single angiographic view. Functional stenosis is defined by FFR 0.80.

Our study involved 223 vessels from 172 patients. Using invasive FFR as a reference, the Pearson correlation coefficient of ICA-FFR was 0.93. ICA-FFR showed a high AUC (AUC = 0.96) and accuracy (91.9) in predicting functional stenosis.

The proposed model accurately compensates for flow to side branches without their geometry in ICA-FFR analysis. ICA-FFR analysis exhibits high feasibility and diagnostic performance in identifying functional stenosis.

Several methods for measuring IMR derived from angiography have been developed. AngioIMR is a novel method for the assessment of angiography-derived IMR with no requirement for a wire and hyperemia. The prognostic value of AngioIMR is unknown in STEMI patients. We aimed to provide the prognostic value of AngioIMR in patients with ST-elevation myocardial infarction (STEMI).

This study included patients with STEMI who underwent invasive coronary angiography and primary percutaneous coronary intervention (PPCI). AngioIMR was calculated using computational flow and pressure simulation immediately after PPCI. The presence of significant coronary microvascular dysfunction was defined as AngioIMR > 40. The primary outcome was a composite of all cause death or hospitalization for heart failure (MACE).

A total of 178 patients were included (65.0 ± 12.8 years on average, 74 % male gender). An AngioIMR > 40 was found in 72 patients. During a median follow-up of 2.9 (2.3-6.9) years, a primary endpoint was observed in 56 patients. By Kaplan-Meier analysis, the risk of MACE was significantly higher in patients with AngioIMR > 40 (log-rank P < 0.01). An Angio IMR > 40 was significantly associated with the occurrence of the primary endpoint in univariate (70 % vs 27 %; hazard ratio 4.519; 95 % CI: 2.550-8.009; p < 0.0001) and multivariate analysis (Hazard ratio 4.282; 95 % CI: 2.325-7.886; p < 0.0001). AngioIMR model showed incremental prognostic value compared to a model with clinical and imaging risk predictors (C-index 0.84 vs 0.79; p = 0.04).

Elevated AngioIMR showed a independent prognostic significance in STEMI patients. In addition to well-known risk factors, assessment of coronary microvascular dysfunction can be a feasible approach for early prevention and a therapeutic target in STEMI patients.

The association between coronary physiological progression and clinical outcomes has not been investigated. A total of 421 patients who underwent serial coronary angiography at least 6 months apart were included. Total physiological atherosclerotic burden was characterized by sum of quantitative flow ratio in 3 epicardial vessels (3V-QFR). The relationships of the 3V-QFR and its longitudinal change (△3V-QFR) with major adverse cardiovascular events (MACE) were explored. 3V-QFR values derived from follow-up angiograms were slightly lower compared with baseline (2.85 [2.77, 2.90] vs 2.86 [2.80, 2.90], P < .001). The median △3V-QFR value was -0.01 (-0.05, 0.02). The multivariable models demonstrated that follow-up 3V-QFR and △3V-QFR were independently associated with MACE (both P < .05). Patients with both low follow-up 3V-QFR (≤2.78) and low △3V-QFR (≤-0.05) presented 3 times higher risk of MACE than those without (hazard ratio: 2.953, 95% confidence interval 1.428-6.104, P = .003). Furthermore, adding patient-level 3V-QFR and △3V-QFR to clinical model significantly improved the predictability for MACE. In conclusion, total physiological atherosclerotic burden and its progression can provide incremental prognostic value over clinical characteristics, supporting the use of coronary physiology in the evaluation of disease progression and for the identification of vulnerable patients.

Risk stratification of patients with symptomatic nonobstructive coronary artery disease remains uncertain. Our study assessed the clinical value of single-vessel, multivessel, and 3-vessel computational angiography-derived fractional flow reserve (caFFR) measurement in patients with nonobstructive coronary artery disease.

We enrolled patients with ≤50% stenosis with a caFFR value ≥0.8 in all 3 coronary arteries on coronary angiography. The sum of caFFR values in the 3 vessels was computed for each patient. Patient stratification was based on the median value of the following criteria: single-vessel analysis, multivessel analysis, and 3-vessel analysis. The primary end point of this study was major adverse cardiac events at 5 years, defined as a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. A total of 490 patients were included. The 5-year major adverse cardiac event rates in single-vessel analysis were statistically insignificant between low- and high-caFFR groups (left anterior descending artery [P=0.163]; left circumflex artery [P=0.797]; right coronary artery [P=0.127]). In multivessel analysis, patients in the multiple-vessel low-caFFR group (with 2-3 vessels lower than median value of all coronary arteries) showed an increased risk of 5-year major adverse cardiac events compared with patients in the single-vessel low-caFFR group (0-1 vessel) (hazard ratio [HR], 2.648 [95% CI, 1.141-6.145]; P=0.023). In 3-vessel analysis, patients in the low 3-vessel caFFR group demonstrated a greater 5-year major adverse cardiac event risk than the high 3-vessel caFFR group (HR, 2.43 [95% CI, 1.087-5.433]; P=0.031).

We demonstrated that both multiple-vessel and 3-vessel caFFR measurements serve as valuable prognostic indicators for risk assessment in patients with nonobstructive coronary artery disease.

Although fractional flow reserve (FFR) is the contemporary standard to detect hemodynamically significant coronary stenosis, it remains underused for the need of pressure wire and hyperemic stimulus. Coronary angiography-derived FFR could break through these barriers. The aim of this study was to assess the feasibility and performance of a novel diagnostic modality deriving FFR from invasive coronary angiography (AccuFFRangio) for coronary physiological assessment.

The ACCURATE (Angiography-Derived Fractional Flow Reserve for Functional Evaluation of Coronary Artery Disease) study was a prospective, multicenter study conducted at 5 centers. Patients who had at least 1 lesion with a diameter stenosis of 30% to 90% were eligible. AccuFFRangio was measured on site in real time and compared with invasive FFR measurements in a blinded fashion. Primary end point was the diagnostic accuracy of AccuFFRangio in identifying functional relevant lesions. Between November 2020 and June 2021, pairwise analyses of AccuFFRangio and FFR were performed in 304 coronary arteries. AccuFFRangio showed good correlation (r=0.89; P<0.001) and agreement (mean difference: 0.01±0.06) with FFR. The diagnostic accuracy was 95.07% (95% CI, 91.99%-97.21%), which were significantly exceeded the prespecified target value (P<0.001). The sensitivity, specificity, and area under the receiver operating characteristic curve of 95.83% (95% CI, 89.67%-98.85%), 94.71% (95% CI, 90.73%-97.33%), and 0.972 (95% CI, 0.947-0.988), respectively.

AccuFFRangio derived from coronary angiography alone has high diagnostic accuracy, sensitivity, and specificity compared with FFR. AccuFFRangio bears the potential for increasing the adoption of functional assessment of coronary artery stenosis and improving the use of physiological guided decision-making.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT04814550.

Murray-law based quantitative flow ratio, namely μFR, was recently validated to compute fractional flow reserve (FFR) from coronary angiographic images in the cath lab. Recently, the μFR algorithm was applied to coronary computed tomography angiography (CCTA) and a semi-automated computed μFR (CT-μFR) showed good accuracy in identifying flow-limiting coronary lesions prior to referral of patients to the cath lab. We aimed to evaluate the diagnostic accuracy of an artificial intelligence-powered method for fully automatic CCTA reconstruction and CT-μFR computation, using cath lab physiology as reference standard.

This was a post-hoc blinded analysis of the prospective CAREER trial (NCT04665817). Patients who underwent CCTA, coronary angiography including FFR within 30 days were included. Cath lab physiology standard for determining hemodynamically significant coronary stenosis was defined as FFR≤0.80, or μFR≤0.80 when FFR was not available.

Automatic CCTA reconstruction and CT-μFR computation was successfully achieved in 657 vessels from 242 patients. CT-μFR showed good correlation (r ​= ​0.62, p ​< ​0.001) and agreement (mean difference ​= ​-0.01 ​± ​0.10, p ​< ​0.001) with cath lab physiology standard. Patient-level diagnostic accuracy for CT-μFR to identify patients with hemodynamically significant stenosis was 83.0 ​% (95%CI: 78.3%-87.8 ​%), with sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio of 84.2 ​%, 81.9 ​%, 82.1 ​%, 84.0 ​%, 4.7 and 0.2, respectively. Average analysis time for CT-μFR was 1.60 ​± ​0.34 ​min per patient.

The fully automatic CT-μFR yielded high feasibility and good diagnostic performance in identifying patients with hemodynamically significant stenosis prior to referral of patients to the cath lab.