Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. RESULTS: 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). CONCLUSIONS: Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Impact of vessel volume on thermodilution measurements in patients with coronary microvascular dysfunction.

BACKGROUND: Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques. AIMS: This study aimed to examine the influence of vessel volume on bolus thermodilution measurements. METHODS: We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment. RESULTS: Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001). CONCLUSIONS: In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment.

Impact of coronary CT image quality on the accuracy of the FFRCT Planner.

OBJECTIVE: To assess the accuracy of a virtual stenting tool based on coronary CT angiography (CCTA) and fractional flow reserve (FFR) derived from CCTA (FFRCT Planner) across different levels of image quality. MATERIALS AND METHODS: Prospective, multicenter, single-arm study of patients with chronic coronary syndromes and lesions with FFR ≤ 0.80. All patients underwent CCTA performed with recent-generation scanners. CCTA image quality was adjudicated using the four-point Likert scale at a per-vessel level by an independent committee blinded to the FFRCT Planner. Patient- and technical-related factors that could affect the FFRCT Planner accuracy were evaluated. The FFRCT Planner was applied mirroring percutaneous coronary intervention (PCI) to determine the agreement with invasively measured post-PCI FFR. RESULTS: Overall, 120 patients (123 vessels) were included. Invasive post-PCI FFR was 0.88 ± 0.06 and Planner FFRCT was 0.86 ± 0.06 (mean difference 0.02 FFR units, the lower limit of agreement (LLA) - 0.12, upper limit of agreement (ULA) 0.15). CCTA image quality was assessed as excellent (Likert score 4) in 48.3%, good (Likert score 3) in 45%, and sufficient (Likert score 2) in 6.7% of patients. The FFRCT Planner was accurate across different levels of image quality with a mean difference between FFRCT Planner and invasive post-PCI FFR of 0.02 ± 0.07 in Likert score 4, 0.02 ± 0.07 in Likert score 3 and 0.03 ± 0.08 in Likert score 2, p = 0.695. Nitrate dose ≥ 0.8mg was the only independent factor associated with the accuracy of the FFRCT Planner (95%CI - 0.06 to - 0.001, p = 0.040). CONCLUSION: The FFRCT Planner was accurate in predicting post-PCI FFR independent of CCTA image quality. CLINICAL RELEVANCE STATEMENT: Being accurate in predicting post-PCI FFR across a wide spectrum of CT image quality, the FFRCT Planner could potentially enhance and guide the invasive treatment. Adequate vasodilation during CT acquisition is relevant to improve the accuracy of the FFRCT Planner. KEY POINTS: • The fractional flow reserve derived from coronary CT angiography (FFRCT) Planner is a novel tool able to accurately predict fractional flow reserve after percutaneous coronary intervention. • The accuracy of the FFRCT Planner was confirmed across a wide spectrum of CT image quality. Nitrates dose at CT acquisition was the only independent predictor of its accuracy. • The FFRCT Planner could potentially enhance and guide the invasive treatment.

Rationale and design of the pullback pressure gradient (PPG) global registry.

INTRODUCTION: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum. AIM: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR. METHODS: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events. RESULTS: Recruitment is ongoing and is expected to be completed in the second half of 2023. CONCLUSION: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.

Relationship between coronary volume, myocardial mass, and post-PCI fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) measured after percutaneous coronary intervention (PCI) carries prognostic information. Yet, myocardial mass subtended by a stenosis influences FFR. We hypothesized that a smaller coronary lumen volume and a large myocardial mass might be associated with lower post-PCI FFR. AIM: We sought to assess the relationship between vessel volume, myocardial mass, and post-PCI FFR. METHODS: This was a subanalysis with an international prospective study of patients with significant lesions (FFR ≤ 0.80) undergoing PCI. Territory-specific myocardial mass was calculated from coronary computed tomography angiography (CCTA) using the Voronoi's algorithm. Vessel volume was extracted from quantitative CCTA analysis. Resting full-cycle ratio (RFR) and FFR were measured before and after PCI. We assessed the association between coronary lumen volume (V) and its related myocardial mass (M), and the percent of total myocardial mass (%M) with post-PCI FFR. RESULTS: We studied 120 patients (123 vessels: 94 left anterior descending arteries, 13 left Circumflex arteries, 16 right coronary arteries). Mean vessel-specific mass was 61 ± 23.1 g (%M 39.6 ± 11.7%). The mean post-PCI FFR was 0.88 ± 0.06 FFR units. Post-PCI FFR values were lower in vessels subtending higher mass (0.87 ± 0.05 vs. 0.89 ± 0.07, p = 0.047), and with lower V/M ratio (0.87 ± 0.06 vs. 0.89 ± 0.07, p = 0.02). V/M ratio correlated significantly with post-PCI RFR and FFR (RFR r = 0.37, 95% CI: 0.21-0.52, p < 0.001 and FFR r = 0.41, 95% CI: 0.26-0.55, p < 0.001). CONCLUSION: Post-PCI RFR and FFR are associated with the subtended myocardial mass and the coronary volume to mass ratio. Vessels with higher mass and lower V/M ratio have lower post-PCI RFR and FFR.

Automation of intracoronary continuous thermodilution for absolute coronary flow and microvascular resistance measurements.

AIM: Microvascular resistance reserve (MRR) as derived from continuous intracoronary thermodilution specifically quantifies microvasculature function. As originally described, the technique necessitates reinstrumentation of the artery and manual reprogramming of the infusion pump when performing resting and hyperemic measurements. To simplify and to render this procedure operator-independent, we developed a fully automated method. The aim of the present study is to validate the automated procedure against the originally described one. METHODS AND RESULTS: For the automated procedure, an infusion pump was preprogrammed to allow paired resting-hyperemic thermodilution assessment without interruption. To validate the accuracy of this new approach, 20 automated measurements were compared to those obtained in the same vessels with conventional paired resting-hyperemic thermodilution measurements (i.e., with a sensor pullback at each infusion rate and manual reprogramming of the infusion pump).  A close correlation between the conventional and the automated measuring technique was found for resting flow (Qrest : r = 0.89, mean bias = 2.52; SD = 15.47), hyperemic flow (Qhyper : r = 0.88, mean bias = -2.65; SD = 27.96), resting microvascular resistance (Rµ-rest : r = 0.90, mean bias = 52.14; SD = 228.29), hyperemic microvascular resistance Rµ-hyper : r = 0.92, mean bias = 12.95; SD = 57.80), and MRR (MRR: r = 0.89, mean bias = 0.04, SD = 0.59).  Procedural time was significantly shorter with the automated method (5'25″ ± 1'23″ vs. 4'36″ ± 0'33″, p = 0.013). CONCLUSION: Continuous intracoronary thermodilution-derived measurements of absolute flow, absolute resistance, and MRR can be fully automated. This further shortens and simplifies the procedure when performing paired resting-hyperemic measurements.

Development, validation, and reproducibility of the pullback pressure gradient (PPG) derived from manual fractional flow reserve pullbacks.

Fractional flow reserve (FFR) pullbacks assess the location and magnitude of pressure drops along the coronary artery. The pullback pressure gradient (PPG) quantifies the FFR pullback curve and provides a numeric expression of focal versus diffuse coronary artery disease. This study aims (1) to validate the PPG using manual FFR pullbacks compared with motorized FFR pullbacks as a reference; and (2) to determine the intra- and interoperator reproducibility of the PPG derived from manual FFR pullbacks. Patients with stable coronary artery disease and an FFR ≤ 0.80 were included. All patients underwent FFR pullback evaluation either with a motorized device or manually, depending on the study cohort. The agreement of the PPG between repeated pullbacks was assessed using the Bland-Altman method. Overall, 116 FFR pullback maneuvers (96 manual and 20 motorized) were analyzed. There was excellent agreement between the PPG derived from manual and motorized pullbacks (mean difference -0.01 ± 0.07, 95% limits of agreement [LOA] -0.14 to 0.12). The intra- and interoperator reproducibility of PPG derived from manual pullbacks were excellent (mean difference <0.01, 95% LOA -0.11 to 0.12, and mean difference <0.01, 95% LOA -0.12 to 0.11, respectively). The duration of the pullback maneuver did not impact the reproducibility of the PPG (r = 0.12, 95% CI: -0.29 to 0.49, p = 0.567). Manual pullbacks allow for an accurate PPG calculation. The inter- and intraoperator reproducibility of PPG derived from manual pullbacks were excellent.

Diagnostic performance of angiography-derived fractional flow reserve in patients with NSTEMI.

Noninvasive methods of estimating invasively measured fractional flow reserve (FFRinvasive ) are actively being explored, aiming to avoid the use of an invasive pressure wire and the administration of hyperemia-inducing drugs. Coronary angiography-derived FFR (FFRangio ) has already demonstrated its diagnostic performance in the context of stable coronary artery disease. However, its applicability in the context of non-ST-segment elevation myocardial infarction (NSTEMI) has yet to be established. We sought to determine the diagnostic performance of FFRangio exclusively in patients presenting with NSTEMI. We performed a prospective, single-center, single-arm, double-blinded study comparing FFR calculated by FFRangio to FFRinvasive in NSTEMI patients. FFRinvasive was measured in all angiographically intermediate lesions (30%-70% stenosis) and was then compared to FFRangio which was calculated at the same position, by a blinded operator. The primary endpoints were the sensitivity and specificity of FFRangio for predicting FFRinvasive using a cut-off value of ≤0.80. Among 100 NSTEMI patients who were screened, 46 patients with 60 vessels in total underwent FFRinvasive and were included in the study. The mean value of FFRinvasive was 0.83 ± 0.3 with 22 (36%) being ≤0.80 while the mean FFRangio was 0.82 ± 0.1 with 22 (36%) being ≤0.80. FFRangio exhibited a sensitivity of 95.5%, a specificity of 97.4%, and a diagnostic accuracy of 96.7%. FFRangio can precisely and noninvasively estimate FFRinvasive in acute coronary syndromes and may have a role in guiding treatment decisions related to angiographically intermediate coronary lesions in this context. WHAT IS KNOWN: FFRangio has demonstrated its diagnostic performance in validation studies, as a noninvasive and cost-effective method in the context of stable coronary artery disease but its performance has never been exclusively evaluated in NSTEMI patients. WHAT IS NEW: The present prospective single-center study demonstrates the excellent diagnostic performance of FFRangio in detecting functionally significant coronary artery stenosis in the setting of NSTEMI, providing more confidence in utilizing FFRangio in this population, avoiding the risk of an invasive pressure wire and the administration of hyperemia-inducing drugs. WHAT IS NEXT: Future randomized trials evaluating FFRangio -guided treatment of coronary artery disease (stable or ACS) are now needed to definitively establish the role of FFRangio in the physiological assessment of coronary lesions.

First report of totally robotically assisted hybrid coronary artery revascularization combining RE-MIDCAB and R-PCI: Case report.

A 62-year-old man presents to the Cardiology Department with a history of angina on exertion. Invasive coronary angiography revealed a severe three vessels coronary artery disease. The "Hybrid Heart Team" successfully performed a fully robotically assisted hybrid revascularization combining robotically enhanced-minimally invasive direct coronary artery bypass on the left anterior descending (LAD) and robotically assisted percutaneous coronary intervention on non-LAD lesions.

Hyperemic hemodynamic characteristics of serial coronary lesions assessed by pullback pressure gradients.

OBJECTIVES: To characterize hemodynamics of serial coronary stenoses using fractional flow reserve (FFR) pullbacks and the pullback pressure gradients (PPG) index. BACKGROUND: The cross-talk between stenoses within the same coronary artery makes the prediction of the functional contribution of each lesion challenging. METHODS AND RESULTS: One-hundred seventeen patients undergoing coronary angiography for stable angina were prospectively recruited. Serial lesions were defined as two or more narrowings with visual diameter stenosis >50% on conventional angiography. Motorized FFR pullback tracings were obtained at 1 mm/s. Pullbacks were visually adjudicated as presenting two, one, and no focal pressure drops. The pattern of disease (i.e., focal or diffuse) was quantified using the PPG index. Twenty-five vessels presented serial lesions (mean PPG 0.48 ± 0.17). Two, one or no focal pressure drops were observed in 40% (n = 10; PPG 0.59 ± 0.17), 52% (n = 13; PPG 0.44 ± 0.12) and 8% of cases (n = 2; PPG 0.27 ± 0.01; p-value = 0.01). Distal FFR was similar between vessels with two, one and no focal pressure drops in the pullback curve (p-value = 0.27). The PPG index independently predicted the presence of two focal pressure drops in the pullback curve (p = 0.04). CONCLUSIONS: FFR pullbacks in serial coronary lesions exhibit three distinct functional patterns. High PPG was associated with pullback curves presenting two pressure drops. The PPG provides a quantitative assessment of the pattern of coronary artery disease in cases with serial lesions and might be useful to assess the appropriateness of percutaneous revascularization.

Simplified Assessment of the Index of Microvascular Resistance.

BACKGROUND: To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR). METHODS: This is a prospective, single-center study of patients with chronic coronary syndromes presenting with nonobstructive coronary artery disease. IMR was obtained using both intravenous (IV) adenosine and intracoronary (IC) papaverine. Each IMR measurement was obtained in duplicate. The primary objective was the agreement between IMR acquired using adenosine and papaverine. Secondary objectives include reproducibility of IMR and time required for the IMR measurement. RESULTS: One hundred and sixteen IMR measurements were performed in 29 patients. The mean age was 68.8 ± 7.24 years, and 27.6% was diabetics. IMR values were similar between papaverine and adenosine (17.7 ± 7.26 and 20.1 ± 8.6, p=0.25; Passing-Bablok coefficient A 0.58, 95% CI -2.42 to 3.53; coefficient B 0.90, 95% CI -0.74 to 1.07). The reproducibility of IMR was excellent with both adenosine and papaverine (ICC 0.78, 95% CI 0.63 to 0.88 and ICC 0.93, 95% CI 0.87 to 0.97). The time needed for microvascular assessment was significantly shortened by the use of IC papaverine (3.23 (2.84, 3.78) mins vs. 5.48 (4.94, 7.09) mins, p < 0.0001). CONCLUSION: IMR can be reliably measured using IC papaverine with similar results compared to intravenous infusion of adenosine with increased reproducibility and reduced procedural time. This approach simplifies the invasive assessment of the coronary microcirculation in the catheterization laboratory.

Motorized fractional flow reserve pullback: Accuracy and reproducibility.

OBJECTIVES: The present study aimed at determining the accuracy and reproducibility of motorized FFR pullbacks in patients with stable coronary artery disease. BACKGROUND: Fractional flow reserve (FFR) is recommended for decision making regarding myocardial revascularization. The distribution of epicardial resistance along coronary vessels can be assessed using FFR pullbacks. METHODS: Duplicated FFR pullbacks were acquired using a motorized device at a speed of 1 mm/s in intermediate coronary stenosis. In addition, a single FFR value was measured at an anatomical landmark. The agreement between FFR measurements was assessed using the Bland-Altman method, Pearson's correlation coefficient and area under the pullback curve (AUPC). RESULTS: In 20 vessels, 37,326 FFR values were obtained. The mean FFR from the pullbacks was 0.91 ± 0.08 whereas the mean FFR at the distal location was 0.85 ± 0.09. The mean difference between pullbacks was -0.002 (LOA -0.058 to 0.054). The difference in AUPC between the two FFR pullbacks was 2.1 ± 1.6%. At pre-specified anatomical locations, the mean difference between the FFR derived from the pullback data and the measured FFR was 0 (LOA -0.040 to 0.039). The repeatability of the distal FFR measurement was high (bias -0.003, LOA -0.046 to 0.041). CONCLUSION: A motorized FFR pullback was accurate to assess the distribution of epicardial resistance in patients with intermediate coronary artery disease. The reproducibility of the FFR pullback was high. Further studies are required to determine the potential usefulness of a hyperemic FFR pullback strategy for decision making and treatment planning.

Vessel Fractional Flow Reserve and Graft Vasculopathy in Heart Transplant Recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the Achilles' heel of long-term survival after heart transplantation (HTx). The severity and extent of CAV is graded with conventional coronary angiography (COR) which has several limitations. Recently, vessel fractional flow reserve (vFFR) derived from COR has emerged as a diagnostic computational tool to quantify the functional severity of coronary artery disease. PURPOSE: The present study assessed the usefulness of vFFR to detect CAV in HTx recipients. METHODS: In HTx patients referred for annual check-up, undergoing surveillance COR, the extent of CAV was graded according to the criteria proposed by the international society of heart and lung transplantation (ISHLT). In addition, three-dimensional coronary geometries were constructed from COR to calculate pressure losses using vFFR. RESULTS: In 65 HTx patients with a mean age of 53.7 ± 10.1 years, 8.5 years (IQR 1.90, 15.2) years after HTx, a total number of 173 vessels (59 LAD, 61 LCX, and 53 RCA) were analyzed. The mean vFFR was 0.84 ± 0.15 and median was 0.88 (IQR 0.79, 0.94). A vFFR ≤ 0.80 was present in 24 patients (48 vessels). HTx patients with a history of ischemic cardiomyopathy (ICMP) had numerically lower vFFR as compared to those with non-ICMP (0.70 ± 0.22 vs. 0.79 ± 0.13, p = 0.06). The use of vFFR reclassified 31.9% of patients compared to the anatomical ISHLT criteria. Despite a CAV score of 0, a pathological vFFR ≤ 0.80 was detected in 8 patients (34.8%). CONCLUSION: The impairment in epicardial conductance assessed by vFFR in a subgroup of patients without CAV according to standard ISHLT criteria suggests the presence of a diffuse vasculopathy undetectable by conventional angiography. Therefore, we speculate that vFFR may be useful in risk stratification after HTx.

Coronary computed tomography angiography for heart team decision-making in multivessel coronary artery disease.

Aims: Coronary computed tomography angiography (CTA) has emerged as a non-invasive diagnostic method for patients with suspected coronary artery disease, but its usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the agreement between separate heart teams on treatment decision-making based on either coronary CTA or conventional angiography. Methods and results: Separate heart teams composed of an interventional cardiologist, a cardiac surgeon, and a radiologist were randomized to assess the coronary artery disease with either coronary CTA or conventional angiography in patients with de novo left main or three-vessel coronary artery disease. Each heart team, blinded for the other imaging modality, quantified the anatomical complexity using the SYNTAX score and integrated clinical information using the SYNTAX Score II to provide a treatment recommendations based on mortality prediction at 4 years: coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or equipoise between CABG and PCI. The primary endpoint was the agreement between heart teams on the revascularization strategy. The secondary endpoint was the impact of fractional flow reserve derived from coronary CTA (FFRCT) on treatment decision and procedural planning. Overall, 223 patients were included. A treatment recommendation of CABG was made in 28% of the cases with coronary CTA and in 26% with conventional angiography. The agreement concerning treatment decision between coronary CTA and conventional angiography was high (Cohen's kappa 0.82, 95% confidence interval 0.74-0.91). The heart teams agreed on the coronary segments to be revascularized in 80% of the cases. FFRCT was available for 869/1108 lesions (196/223 patients). Fractional flow reserve derived from coronary CTA changed the treatment decision in 7% of the patients. Conclusion: In patients with left main or three-vessel coronary artery disease, a heart team treatment decision-making based on coronary CTA showed high agreement with the decision derived from conventional coronary angiography suggesting the potential feasibility of a treatment decision-making and planning based solely on this non-invasive imaging modality and clinical information. Trial registration number: NCT02813473.

Real-world clinical utility and impact on clinical decision-making of coronary computed tomography angiography-derived fractional flow reserve: lessons from the ADVANCE Registry.

Aims: Non-invasive assessment of stable chest pain patients is a critical determinant of resource utilization and clinical outcomes. Increasingly coronary computed tomography angiography (CCTA) with selective CCTA-derived fractional flow reserve (FFRCT) is being used. The ADVANCE Registry, is a large prospective examination of using a CCTA and FFRCT diagnostic pathway in real-world settings, with the aim of determining the impact of this pathway on decision-making, downstream invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular events (MACE). Methods and results: A total of 5083 patients with symptoms concerning for coronary artery disease (CAD) and atherosclerosis on CCTA were enrolled at 38 international sites from 15 July 2015 to 20 October 2017. Demographics, symptom status, CCTA and FFRCT findings, treatment plans, and 90 days outcomes were recorded. The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management plans occurred in 66.9% [confidence interval (CI): 64.8-67.6] of patients. Non-obstructive coronary disease was significantly lower in ICA patients with FFRCT ≤0.80 (14.4%) compared to patients with FFRCT >0.80 (43.8%, odds ratio 0.19, CI: 0.15-0.25, P < 0.001). In total, 72.3% of subjects undergoing ICA with FFRCT ≤0.80 were revascularized. No death/myocardial infarction (MI) occurred within 90 days in patients with FFRCT >0.80 (n = 1529), whereas 19 (0.6%) MACE [hazard ratio (HR) 19.75, CI: 1.19-326, P = 0.0008] and 14 (0.3%) death/MI (HR 14.68, CI 0.88-246, P = 0.039) occurred in subjects with an FFRCT ≤0.80. Conclusions: In a large international multicentre population, FFRCT modified treatment recommendation in two-thirds of subjects as compared to CCTA alone, was associated with less negative ICA, predicted revascularization, and identified subjects at low risk of adverse events through 90 days.

Diagnostic performance of angiography-derived fractional flow reserve: a systematic review and Bayesian meta-analysis.

Aims: Pressure-wire assessment of coronary stenosis is considered the invasive reference standard for detection of ischaemia-generating lesions. Recently, methods to estimate the fractional flow reserve (FFR) from conventional angiography without the use of a pressure wire have been developed, and were shown to have an excellent diagnostic accuracy. The present systematic review and meta-analysis aimed at determining the diagnostic performance of angiography-derived FFR for the diagnosis of haemodynamically significant coronary artery disease. Methods and results: A systematic review and meta-analysis of studies assessing the diagnostic performance of angiography-derived FFR systems were performed. The primary outcome of interest was pooled sensitivity and specificity. Thirteen studies comprising 1842 vessels were included in the final analysis. A Bayesian bivariate meta-analysis yielded a pooled sensitivity of 89% (95% credible interval 83-94%), specificity of 90% (95% credible interval 88-92%), positive likelihood ratio (+LR) of 9.3 (95% credible interval 7.3-11.7) and negative likelihood ratio (-LR) of 0.13 (95% credible interval 0.07-0.2). The summary area under the receiver-operating curve was 0.84 (95% credible interval 0.66-0.94). Meta-regression analysis did not find differences between the methods for pressure-drop calculation (computational fluid dynamics vs. mathematical formula), type of analysis (on-line vs. off-line) or software packages. Conclusion: The accuracy of angiography-derived FFR was good to detect haemodynamically significant lesions with pressure-wire measured FFR as a reference. Computational approaches and software packages did not influence the diagnostic accuracy of angiography-derived FFR. A diagnostic strategy trial with angiography-derived FFR evaluating clinical endpoints is warranted.

How to measure quality of care in patients presenting with STEMI? A single-centre experience.

OBJECTIVE: The evaluation of the quality of care delivered to patients with acute coronary syndromes is becoming increasingly important. Due to novel regulations permitting the installation of new catheterization laboratories in Belgium, the Flemish government initiated a project to measure quality of care in patients with an ST-elevated myocardial infarction (STEMI) by measuring four quality indicators: prescription of ACE inhibitor, beta blocker or aspirin on discharge and unadjusted mortality. However, we are not convinced that these four indicators will provide sufficient information on the quality of care in our hospitals. Hence, we performed a retrospective analysis on a larger set of parameters and evaluated their applicability as indicators of quality of care. METHODS: We measured 38 indicators in 153 patients (69 transferred and 84 on-site) with a STEMI who presented at, or were transferred to the UZ Brussels in 2013 and received percutaneous coronary intervention (PCI). RESULTS: The unadjusted overall mortality was 7.2% (n = 11/153). Important differences in unadjusted mortality were observed between the on-site and transferred patients (10.7%, n = 9 vs 2.9%, n = 2, P = 0.112), which were attributed to the initial condition at presentation and a larger proportion of cardiogenic shocks in the on-site group. Discharge medication highly corresponded with the ESC guidelines. CONCLUSION: We demonstrate that the proposed quality indicators do not provide sufficient information to compare hospitals and that it is of utmost importance to weigh the mortality according to risk profile.

FFRct use for acute chest pain triage in the emergency department: a cost-effectiveness analysis.

AIMS: To model and assess the cost-effectiveness of CT-based fractional flow reserve (FFRct) for a population of low to intermediate risk patients for coronary artery disease (CAD) presenting to the emergency department (ED) with acute chest pain. METHODS AND RESULTS: Using a decision tree model with a 1 year time horizon and from a health care perspective, two diagnostic pathways using FFRct are compared to current clinical routine combining coronary computed tomography angiography (CCTA) with an exercise test. Model data are drawn from the literature and nationally reported data. Outcomes are assessed as the number of avoided invasive coronary angiographies (ICAs) showing no obstructive CAD and quality of life (QoL) in a theoretical cohort of 1000 patients. Sensitivity analyses are performed to test the robustness of the results. Determining FFRct when CCTA is inconclusive is a cost-effective and dominant strategy with a potential saving of 198€/patient, 154 avoided unnecessary ICA showing no obstructive CAD (uICA)/1000 patients and an average improvement in QoL of 0.008 QALY/patient. With an additional 574€/patient, 8 avoided uICA/1000 patients and an improvement in QoL of 0.001 QALY/patient, a strategy where FFRct is always performed is cost-effective only when considering high cost-effectiveness thresholds. CONCLUSIONS: For patients presenting to the ED with acute chest pain and a low to intermediate pre-test probability of CAD, a diagnostic strategy where FFRct is determined after an inconclusive CCTA is cost-effective. Clinical trials investigating both sensitivity and specificity of FFRct, as well as QoL associated with the use of this technology in this setting are warranted.

The Influence Of Epicardial Resistance On Microvascular Resistance Reserve.

BACKGROUND: The optimal index of microvascular function should be specific for the microvascular compartment. Yet, coronary flow reserve (CFR), despite being widely used to diagnose coronary microvascular dysfunction (CMD), is influenced by both epicardial and microvascular resistance. Conversely, microvascular resistance reserve (MRR) adjusts for fractional flow reserve (FFR), and thus is theoretically independent of epicardial resistance. OBJECTIVES: We tested the hypothesis that MRR, unlike CFR, is not influenced by increasing epicardial resistance, and thus is a more specific index of microvascular function. METHODS: In a cohort of 16 patients that had undergone proximal left anterior descending artery stenting, we created four grades of artificial stenosis (no stenosis, mild, moderate, and severe) using a coronary angioplasty balloon inflated to different degrees within the stent. For each stenosis grade, we calculated CFR and MRR using continuous thermodilution (64 measurements of each) in order to assess their response to changing epicardial resistance. RESULTS: Graded balloon inflation resulted in a significant sequential decrease in mean FFR (no stenosis: 0.82 ±0.05; mild: 0.72 ±0.04; moderate: 0.61 ±0.05; severe: 0.48 ±0.09, p<0.001). This translated into a linear decrease in mean hyperaemic coronary flow (no stenosis: 170.5 ±66.8 ml/min; mild: 149.8 ±58.8 ml/min; moderate: 124.4 ±53.0 ml/min; severe: 94.0 ±45.2 ml/min, p<0.001). CFR exhibited a marked linear decrease with increasing stenosis (no stenosis: 2.5 ±0.9; mild: 2.2 ±0.8; moderate: 1.8 ±0.7; severe: 1.4 ±0.6), corresponding to a decrease of 0.3 for a decrease in FFR of 0.1 (p<0.001). In contrast, MRR exhibited a negligible decrease across all stenosis grades (no stenosis: 3.0 ±1.0; mild: 3.0 ±1.0; moderate: 2.9 ±1.0; severe: 2.8 ±1.0), corresponding to a decrease of just 0.05 for a decrease in FFR of 0.1 (p<0.001). CONCLUSION: MRR, unlike CFR, is minimally influenced by epicardial resistance, and thus should be considered the more specific index of microvascular function. This suggests that MRR can also reliably evaluate microvascular function in patients with significant epicardial disease.