Renal Dysfunction Increases Risk of Adverse Cardiovascular Events in 5-Year Follow-Up Study of Intermediate Coronary Artery Lesions.

BACKGROUND Progression of chronic coronary syndrome (CCS) is influenced by chronic kidney disease (CKD). This 5-year follow-up study aimed to assess 100 patients with 118 intermediate coronary artery lesions evaluated by fractional flow reserve (FFR) and intravascular imaging stratified according to renal function. MATERIAL AND METHODS This prospective study enrolled patients with intermediate coronary stenosis identified by coronary angiogram. Patients with severe renal dysfunction (estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m²) were excluded from the study. The remaining were divided into 2 groups according to eGFR: 45-60 ml/min/1.73 m² for mild-to-moderate renal dysfunction and >60 ml/min/1.73 m² for no renal dysfunction. We analyzed intermediate-grade stenoses (40-80% as assessed in coronary angiography) with the use of optical coherence tomography (OCT), FFR, and intravascular ultrasound (IVUS). RESULTS Renal dysfunction patients were older (67.7±8.1 vs 63.6±9.7 years, P=0.044). Lesion characteristics, including plaque type and minimal lumen area in OCT, showed no significant differences between the renal dysfunction and no renal dysfunction groups. Thin-cap fibroatheroma, calcific plaques, lipidic plaques, and fibrous plaques had similar prevalence. FFR values and IVUS parameters did not significantly differ between the groups. Over a 5-year follow-up, individuals with mild-to-moderate renal dysfunction had an elevated risk of all-cause mortality and major adverse cardiovascular events in multivariate analyses adjusted for age and sex. CONCLUSIONS Mild-to-moderate renal dysfunction was not associated with significant differences in OCT- and IVUS-derived plaque morphology nor with functional indices characterizing intermediate-grade coronary stenoses. Renal dysfunction was related to a higher risk of all-cause mortality and major adverse cardiovascular events prevalence in 5-year follow-up.

Quantitative flow ratio versus fractional flow reserve for Heart Team decision-making in multivessel disease: the randomised, multicentre DECISION QFR trial.

BACKGROUND: Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time. AIMS: The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated. METHODS: Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa. RESULTS: The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00]). CONCLUSIONS: QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

Agreement of Fractional Flow Reserve Estimated by Computed Tomography With Invasively Measured Fractional Flow Reserve: A Systematic Review and Meta-Analysis.

BACKGROUND: Fractional flow reserve (FFR) is the ratio of blood pressure measured distal to a stenosis and pressure proximal to a stenosis. FFR can be estimated noninvasively using computed tomography (CT) although the usefulness of this technique remains controversial. This meta-analysis evaluated the agreement of FFR estimated by CT (FFR-CT) with invasively measured FFR. The study also evaluated the diagnostic accuracy of FFR-CT, defined as the ability of FFR-CT to classify lesions as hemodynamically significant (invasive FFR ≤0.8) or insignificant (invasive FFR >0.8). METHODS AND RESULTS: Forty-three studies reporting on 7291 blood vessels from 5236 patients were included. A moderate positive linear relationship between FFR-CT and invasively measured FFR was observed (Spearman correlation coefficient: 0.67). Agreement between the 2 measures increased as invasively measured FFR values approached 1. The overall diagnostic accuracy, sensitivity and specificity of FFR-CT were 82.2%, 80.9%, and 83.1%, respectively. Diagnostic accuracy of 90% could be demonstrated for FFR-CT values >0.90 and <0.49. The diagnostic accuracy of off-site tools was 79.4% and the diagnostic accuracy of on-site tools was 84.1%. CONCLUSIONS: The agreement between FFR-CT and invasive FFR is moderate although agreement is highest in vessels with FFR-CT >0.9. Diagnostic accuracy varies widely with FFR-CT value but is above 90% for FFR-CT values >0.90 and <0.49. Furthermore, on-site and off-site tools have similar performance. Ultimately, FFR-CT may be a useful adjunct to CT coronary angiography as a gatekeeper for invasive coronary angiogram.

Differential Effect of Aortic Valve Replacement for Severe Aortic Stenosis on Hyperemic and Resting Epicardial Coronary Pressure Indices.

BACKGROUND: Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta-analysis was to study immediate and long-term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). METHODS AND RESULTS: Lesion-specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long-term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired t tests. Immediately after TAVR, FFR decreased significantly (-0.0130±0.0406 SD, P: 0.0002) while NHPR remained stable (0.0003±0.0675, P: 0.9675). Long-term after TAVR, FFR decreased significantly (-0.0230±0.0747, P: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699, P: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441, P: 0.0015). Sensitivity analysis confirmed our results in borderline lesions. CONCLUSIONS: TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut-offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.

Coronary Microvascular Function Following Severe Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. METHODS: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging. RESULTS: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (ß, -0.67 [95% CI, -1.21 to -0.13]; P=0.016), lower stress myocardial blood flow (ß, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P=0.001), and higher stress coronary vascular resistance (ß, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P=0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow (r=0.71; P<0.001), independent of hemodynamics. CONCLUSIONS: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease.

Interplay Between Systemic Inflammation, Myocardial Injury, and Coronary Microvascular Dysfunction in Rheumatoid Arthritis: Results From the LiiRA Study.

BACKGROUND: Coronary microvascular dysfunction as measured by myocardial flow reserve (MFR) is associated with increased cardiovascular risk in rheumatoid arthritis (RA). The objective of this study was to determine the association between reducing inflammation with MFR and other measures of cardiovascular risk. METHODS AND RESULTS: Patients with RA with active disease about to initiate a tumor necrosis factor inhibitor were enrolled (NCT02714881). All subjects underwent a cardiac perfusion positron emission tomography scan to quantify MFR at baseline before tumor necrosis factor inhibitor initiation, and after tumor necrosis factor inhibitor initiation at 24 weeks. MFR <2.5 in the absence of obstructive coronary artery disease was defined as coronary microvascular dysfunction. Blood samples at baseline and 24 weeks were measured for inflammatory markers (eg, high-sensitivity C-reactive protein [hsCRP], interleukin-1b, and high-sensitivity cardiac troponin T [hs-cTnT]). The primary outcome was mean MFR before and after tumor necrosis factor inhibitor initiation, with Δhs-cTnT as the secondary outcome. Secondary and exploratory analyses included the correlation between ΔhsCRP and other inflammatory markers with MFR and hs-cTnT. We studied 66 subjects, 82% of which were women, mean RA duration 7.4 years. The median atherosclerotic cardiovascular disease risk was 2.5%; 47% had coronary microvascular dysfunction and 23% had detectable hs-cTnT. We observed no change in mean MFR before (2.65) and after treatment (2.64, P=0.6) or hs-cTnT. A correlation was observed between a reduction in hsCRP and interleukin-1b with a reduction in hs-cTnT. CONCLUSIONS: In this RA cohort with low prevalence of cardiovascular risk factors, nearly 50% of subjects had coronary microvascular dysfunction at baseline. A reduction in inflammation was not associated with improved MFR. However, a modest reduction in interleukin-1b and no other inflammatory pathways was correlated with a reduction in subclinical myocardial injury. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02714881.

Predictive value of plaque characteristics for identification of lesions causing ischemia.

BACKGROUND: Functional assessment using fractional flow reserve (FFR) and anatomical assessment using optical coherence tomography (OCT) are used in clinical practice for patients with intermediate coronary stenosis. Moreover, coronary computed tomography angiography (CTA) is a common noninvasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. This study aimed to investigate the association between FFR and plaque characteristics assessed using coronary CTA and OCT for intermediate coronary stenosis. METHODS: Based on a prospective multicenter registry, 159 patients having 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography, and both FFR measurements and OCT examinations were performed during angiography. A stenotic lesion identified with FFR ≤0.80 was deemed diagnostic of an ischemia-causing lesion. The predictive value of plaque characteristics assessed using coronary CTA and OCT for identifying lesions causing ischemia was analyzed. RESULTS: Stenosis severity and plaque characteristics on coronary CTA and OCT differed between lesions that caused ischemia and those that did not. In multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]=2.78; P=0.038), thrombus (OR=5.13; P=0.042), plaque rupture (OR=3.25; P=0.017), and intimal vasculature on OCT (OR=2.57; P=0.012) were independent predictors of ischemic lesions. Increasing the number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia. CONCLUSIONS: Comprehensive anatomical evaluation of coronary stenosis may provide additional supportive information for predicting the lesions causing ischemia.

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. METHODS AND RESULTS: This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CONCLUSIONS: CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

Diagnostic and prognostic performance of artificial intelligence-based fully-automated on-site CT-FFR in patients with CAD.

Currently, clinically available coronary CT angiography (CCTA) derived fractional flow reserve (CT-FFR) is time-consuming and complex. We propose a novel artificial intelligence-based fully-automated, on-site CT-FFR technology, which combines the automated coronary plaque segmentation and luminal extraction model with reduced order 3 dimentional (3D) computational fluid dynamics. A total of 463 consecutive patients with 600 vessels from the updated China CT-FFR study in Cohort 1 undergoing both CCTA and invasive fractional flow reserve (FFR) within 90 d were collected for diagnostic performance evaluation. For Cohort 2, a total of 901 chronic coronary syndromes patients with index CT-FFR and clinical outcomes at 3-year follow-up were retrospectively analyzed. In Cohort 3, the association between index CT-FFR from triple-rule-out CTA and major adverse cardiac events in patients with acute chest pain from the emergency department was further evaluated. The diagnostic accuracy of this CT-FFR in Cohort 1 was 0.82 with an area under the curve of 0.82 on a per-patient level. Compared with the manually dependent CT-FFR techniques, the operation time of this technique was substantially shortened by 3 times and the number of clicks from about 60 to 1. This CT-FFR technique has a highly successful (> 99%) calculation rate and also provides superior prediction value for major adverse cardiac events than CCTA alone both in patients with chronic coronary syndromes and acute chest pain. Thus, the novel artificial intelligence-based fully automated, on-site CT-FFR technique can function as an objective and convenient tool for coronary stenosis functional evaluation in the real-world clinical setting.

Interaction of AI-Enabled Quantitative Coronary Plaque Volumes on Coronary CT Angiography, FFRCT, and Clinical Outcomes: A Retrospective Analysis of the ADVANCE Registry.

BACKGROUND: Luminal stenosis, computed tomography-derived fractional-flow reserve (FFRCT), and high-risk plaque features on coronary computed tomography angiography are all known to be associated with adverse clinical outcomes. The interactions between these variables, patient outcomes, and quantitative plaque volumes have not been previously described. METHODS: Patients with coronary computed tomography angiography (n=4430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry underwent artificial intelligence-enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume and each plaque subtype were derived using receiver-operator characteristic curve analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFRCT, and translesional delta-FFRCT. Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events, late revascularization, a composite of the two, and cardiovascular death and myocardial infarction. RESULTS: At one year, 55 patients (1.2%) had experienced major adverse cardiac events, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis, and FFRCT, total plaque volume above the receiver-operator characteristic curve-derived optimal cutoff (total plaque volume >564 mm3) was associated with the major adverse cardiac event/late revascularization composite (adjusted hazard ratio, 1.515 [95% CI, 1.093-2.099]; P=0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both major adverse cardiac event/late revascularization (total percent atheroma volume >24.4%; hazard ratio, 2.046 [95% CI, 1.474-2.839]; P<0.0001) and cardiovascular death/myocardial infarction (total percent atheroma volume >37.17%, hazard ratio, 4.53 [95% CI, 1.943-10.576]; P=0.0005). Calcified, noncalcified, and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/myocardial infarction in analyses stratified by median plaque volumes. CONCLUSIONS: Analysis of the ADVANCE registry using artificial intelligence-enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFRCT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02499679.

Fluid-filled versus sensor-tipped pressure guidewires for FFR and Pd/Pa measurement; PW-COMPARE study.

BACKGROUND: Fluid-filled pressure guidewires are unaffected by the previously inevitable hydrostatic pressure gradient (HPG). This study aimed to compare simultaneous pressure measurements with fluid-filled and sensor-tipped pressure guidewires. METHODS: Fifty patients underwent fractional flow reserve (FFR) and Pd/Pa measurement with a fluid-filled and a sensor-tipped pressure guidewire simultaneously. To assess maneuverability, patients were randomized with respect to which pressure guidewire was used to cross the lesion first. Lateral fluoroscopy was used to estimate height difference between catheter tip and distal wire position (and thus HPG). Agreement between pressure measurements was studied. RESULTS: Measurements were performed in LM (4% (n = 2)), LAD (44% (n = 22)), LCX (26% (n = 13)), and RCA (26% (n = 13)). Simultaneous pressure measurements showed excellent agreement (mean FFR difference - 0.01 ± 0.03 (r = 0.959, p < 0.001), mean Pd/Pa difference - 0.01 ± 0.04 (r = 0.929, p < 0.001)). FFR was ≤0.80 in 42.6% (n = 20) with fluid-filled FFR measurements versus 46.8% (n = 22) by sensor-tipped FFR measurements. Mean height difference was 15 ± 34 mm, and strongly dependent on the coronary artery (LAD 45 ± 10 mm, LCX -23 ± 16 mm, RCA -13 ± 17 mm). There was a strong correlation between height difference and difference in pressure ratios between sensor-tipped and fluid-filled pressure guidewires (FFR r = -0.850, p < 0.001; Pd/Par = -0.641, p < 0.001). Largest FFR differences were present in the LAD (-0.04 ± 0.02). After HPG correction, mean difference between HPG-corrected sensor-tipped FFR and fluid-filled FFR was 0.00 ± 0.02, mean Pd/Pa difference was 0.01 ± 0.03. CONCLUSIONS: This study shows excellent overall correlation between FFR and Pd/Pa measurements with both pressure guidewires. Differences measured with fluid-filled and sensor-tipped pressure guidewires are vessel-specific and attributable to hydrostatic pressure gradients (NCT04802681).

Cardiac CT: Competition, complimentary or confounder.

Coronary CT angiography (CCTA) has been gradually adopted into clinical practice over the last two decades. CCTA has high diagnostic accuracy, prognostic value, and unique features such as assessment of plaque composition. CCTA-derived functional assessment techniques such as fractional flow reserve and CT perfusion are also available and can increase the diagnostic specificity of the modality. These properties propound CCTA as a competitor of functional testing in diagnosis of obstructive CAD, however, utilizing CCTA in a concomitant fashion to potentiate the performance of the latter can lead to better patient care and may provide more accurate prognostic information. Although multiple diagnostic challenges such as evaluation of calcified segments, stents, and small distal vessels still exist, the technologic developments in hardware as well as growing incorporation of artificial intelligence to daily practice are all set to augment the diagnostic and prognostic role of CCTA in cardiovascular disorders.

Optical Coherence Tomography-Based Functional Stenosis Assessment: FUSION-A Prospective Multicenter Trial.

BACKGROUND: Intravascular imaging and intracoronary physiology may both be used to guide and optimize percutaneous coronary intervention; however, they are rarely used together. The virtual flow reserve (VFR) is an optical coherence tomography (OCT)-based model of fractional flow reserve (FFR) facilitating the assessment of the physiological significance of coronary lesions. We aimed to validate the VFR assessment of intermediate coronary artery stenoses. METHODS: FUSION (Validation of OCT-Based Functional Diagnosis of Coronary Stenosis) was a multicenter, prospective, observational study comparing OCT-derived VFR to invasive FFR. VFR was mathematically derived from a lumped parameter flow model based on 3-dimensional lumen morphology. Patients undergoing coronary angiography with intermediate angiographic stenosis (40%-90%) requiring physiological assessment were enrolled. Investigational sites were blinded to the VFR analysis, and all OCT and FFR data were reviewed by an independent core laboratory. The coprimary end points were the sensitivity and specificity of VFR against FFR as the reference standard, each of which was tested against prespecified performance goals. RESULTS: After core laboratory review, 266 vessels in 224 patients from 25 US centers were included in the analysis. The mean angiographic diameter stenosis was 65.5%±14.9%, and the mean FFR was 0.83±0.11. Overall accuracy, sensitivity, and specificity of VFR versus FFR using a binary cutoff point of 0.80 were 82.0%, 80.4%, and 82.9%, respectively. The 97.5% lower confidence bound met the prespecified performance goal for sensitivity (71.6% versus 70%; P=0.01) and specificity (76.6% versus 75%; P=0.01). The area under the curve was 0.88 (95% CI, 0.84-0.92; P<0.0001). CONCLUSIONS: OCT-derived VFR demonstrates high sensitivity and specificity for predicting invasive FFR. Integrating high-resolution intravascular imaging with imaging-derived physiology may provide synergistic benefits as an adjunct to percutaneous coronary intervention. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04356027.

Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Consensus document on the clinical application of invasive functional coronary angiography from the Japanese Association of Cardiovascular Intervention and Therapeutics.

Invasive functional coronary angiography (FCA), an angiography-derived physiological index of the functional significance of coronary obstruction, is a novel physiological assessment tool for coronary obstruction that does not require the utilization of a pressure wire. This technology enables operators to rapidly evaluate the functional relevance of coronary stenoses during and even after angiography while reducing the burden of cost and complication risks related to the pressure wire. FCA can be used for treatment decision-making for revascularization, strategy planning for percutaneous coronary intervention, and procedure optimization. Currently, various software-computing FCAs are available worldwide, with unique features in their computation algorithms and functions. With the emerging application of this novel technology in various clinical scenarios, the Japanese Association of Cardiovascular Intervention and Therapeutics task force was created to outline expert consensus on the clinical use of FCA. This consensus document advocates optimal clinical applications of FCA according to currently available evidence while summarizing the concept, history, limitations, and future perspectives of FCA along with globally available software.

Diagnostic performance of pressure-bounded coronary flow reserve.

Fluid dynamics studies have proposed that coronary flow reserve can be calculated from coronary artery pressure instead of coronary blood flow. We sought to investigate the diagnostic performance of pressure-bounded coronary flow reserve (pb-CFR) compared with CFR measured by conventional thermodilution method (CFRthermo) in the clinical setting. Pressure guidewire was used to measure CFRthermo and fractional flow reserve (FFR) in left anterior descending coronary artery in 62 patients with stable coronary artery disease. Pb-CFR was calculated only with resting distal coronary artery pressure (Pd), resting aortic pressure (Pa) and FFR. Pb-CFR was moderately correlated with CFRthermo (r = 0.54, P < 0.001). Pb-CFR showed a poor agreement with CFRthermo, presenting large values of mean difference and root mean square deviation (1.5 ± 1.4). Pb-CFR < 2.0 predicted CFRthermo < 2.0 with an accuracy of 79%, sensitivity of 83%, specificity of 78%, positive predictive value of 48%, negative predictive value of 95%. The discordance presenting CFRthermo < 2.0 and pb-CFR ≥ 2.0 was associated with diffuse disease (P < 0.001). The discordance presenting CFRthermo ≥ 2 and pb-CFR < 2 was associated with a high FFR (P = 0.002). Pb-CFR showed moderate correlation and poor agreement with CFRthermo. Pb-CFR might be reliable in excluding epicardial coronary artery disease and microcirculatory disorders.

Impact of sex on the assessment of the microvascular resistance reserve.

BACKGROUND: The microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women. AIM: The aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes. METHODS: From the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men. RESULTS: A total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47-0.96, p = 0.027) and men (HR 0.84, 0.74-0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men. CONCLUSION: The MRR seems to be equally applicable in both women and men with stable coronary artery disease.

Quantitative computed tomography angiography evaluation of the coronary fractional flow reserve in patients with left anterior descending artery myocardial bridging.

PURPOSE: To quantitatively investigate the effect of myocardial bridge (MB) in the left anterior descending artery (LAD) on the fractional flow reserve (FFR). MATERIALS AND METHODS: Three-hundred patients with LAD MB who had undergone coronary artery CT angiography (CCTA) were retrospectively enroled, and 104 normal patients were enroled as the control. The CCTA-derived fractional flow reserve (FFRCT) was measured at the LAD 10 mm proximal (FFR1) and 20-40 mm distal (FFR3) to the MB and at the MB location (FFR2). RESULTS: FFR2 and FFR3 of the MB (with BM only) and MBLA (with both MB and atherosclerosis) groups were significantly (p < 0.01) lower than those of the control. The FFR3 distal to the MB was significantly lower (p < 0.01) than that of the control. The FFRCT of the whole LAD in the MBLA group was significantly (p < 0.05) lower than that of the MB and control group (p < 0.05). MB length (OR 1.061) and MB muscle index (odds ratio or OR 1.007) were two risk factors for abnormal FFRCT, and MB length was a significant independent risk factor for abnormal FFRCT (OR = 1.077). LAD stenosis degree was a risk factor for abnormal FFRCT values (OR 3.301, 95% confidence interval [CI] 1.441-7.562, p = 0.005) and was also a significant independent risk factor (OR = 3.369, 95% CI: 1.392-8.152; p = 0.007) for abnormal FFRCT. CONCLUSION: MB significantly affects the FFRCT of distal coronary artery. For patients with MB without atherosclerosis, the MB length is a risk factor significantly affecting FFRCT, and for patients with MB accompanied by atherosclerosis, LAD stenotic severity is an independent risk factor for FFRCT.

82-rubidium positron emission tomography determined myocardial flow reserve and outcomes following cardiac revascularisation - A multicentre registry study.

BACKGROUND: Finding patients with chronic coronary syndromes (CCS) whom revascularization could benefit, is complicated. Myocardial flow reserve (MFR), a measurement of myocardial perfusion, has proven prognostic value on survival and risk of major adverse cardiac events (MACE). We investigated if MFR identifies who may benefit from revascularization. METHODS: Among 7462 patients from Danish hospitals examined with 82Rb PET between January 2018 and August 2020, patients with ≥5% reversible perfusion defects were followed for MACE and all-cause mortality. Associations between revascularisation (within 90 days) and outcomes according to MFR (< and ≥ 2) was assessed by Cox regression adjusted by inverse probability weighting for demographics, cardiovascular risk factors, comorbidities, and 82Rb PET variables. RESULTS: Of 1806 patients with ≥5% reversible perfusion defect, 893 (49%) had MFR < 2 and 491 underwent revascularisation (36.6% in MFR < 2 versus 17.9% MFR ≥ 2, p < 0.001). During a median follow-up of 37.0 [31.0-45.8 IQR] months, 251 experienced a MACE and 173 died. Revascularisation was associated with lower adjusted risk of all-cause mortality (hazard ratio [HR], 0.51 [95% CI, 0.30-0.88], p = 0.015) and MACE (HR, 0.54 [0.33-0.87], p = 0.012) in patients with MFR < 2 but not MFR ≥ 2 for all-cause mortality (HR 1.33 [0.52-3.40], p = 0.542) and MACE (HR 1.50 [0.79-2.84], p = 0.211). MFR significantly modified the association between revascularisation and MACE, but not all-cause mortality (interaction p-value 0.021 and 0.094, respectively). CONCLUSIONS: Revascularization was associated with improved prognosis among patients with impaired MFR. No association was seen in patients with normal MFR. In patients with regional ischemia, MFR may identify patients with a prognostic benefit from revascularization.

Intravascular Imaging Findings After PCI in Patients With Focal and Diffuse Coronary Artery Disease.

BACKGROUND: Following percutaneous coronary intervention (PCI), optical coherence tomography provides prognosis information. The pullback pressure gradient is a novel index that discriminates focal from diffuse coronary artery disease based on fractional flow reserve pullbacks. We sought to investigate the association between coronary artery disease patterns, defined by coronary physiology, and optical coherence tomography after stent implantation in stable patients undergoing PCI. METHODS AND RESULTS: This multicenter, prospective, single-arm study was conducted in 5 countries (NCT03782688). Subjects underwent motorized fractional flow reserve pullbacks evaluation followed by optical coherence tomography-guided PCI. Post-PCI optical coherence tomography minimum stent area, stent expansion, and the presence of suboptimal findings such as incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were compared between patients with focal versus diffuse disease. Overall, 102 patients (105 vessels) were included. Fractional flow reserve before PCI was 0.65±0.14, pullback pressure gradient was 0.66±0.14, and post-PCI fractional flow reserve was 0.88±0.06. The mean minimum stent area was 5.69±1.99 mm2 and was significantly larger in vessels with focal disease (6.18±2.12 mm2 versus 5.19±1.72 mm2, P=0.01). After PCI, incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were observed in 27.6%, 10.5%, and 51.4% of the cases, respectively. Vessels with focal disease at baseline had a lower prevalence of incomplete stent apposition (11.3% versus 44.2%, P=0.002) and more irregular tissue protrusion (69.8% versus 32.7%, P<0.001). CONCLUSIONS: Baseline coronary pathophysiological patterns are associated with suboptimal imaging findings after PCI. Patients with focal disease had larger minimum stent area and a higher incidence of tissue protrusion, whereas stent malapposition was more frequent in patients with diffuse disease.