The role of advanced physiological guidance in contemporary coronary artery disease management.

PURPOSE OF REVIEW: This review evaluates the emerging role of the pullback pressure gradient (PPG) as a standardized metric for assessing coronary artery disease (CAD) patterns and its implications for clinical decision-making when managing patients undergoing percutaneous coronary interventions (PCIs). By integrating PPG with existing physiological assessments, this review highlights the potential benefits of PPG in predicting treatment outcomes and refining therapeutic strategies for CAD. RECENT FINDINGS: Recent studies, particularly the PPG Global study have demonstrated a strong correlation between PPG values and post-PCI outcomes, revealing that focal disease is associated with improved fractional flow reserve (FFR) and lower rates of adverse events than vessels with diffuse disease (low PPG). Additionally, PPG has been linked to specific atherosclerotic plaque characteristics, indicating its utility in identifying high-risk plaques. The integration of PPG with advanced imaging techniques further enhances the understanding of CAD patterns and their implications for treatment planning. SUMMARY: The PPG represents a significant advancement in the management of CAD, providing a reproducible and objective assessment of coronary artery disease patterns that can inform clinical decision-making. As research continues to explore the relationship among PPG, atherosclerotic characteristics, and patient outcomes, its integration into routine practice is expected to improve the effectiveness of PCI and optimize patient management strategies. Future studies are warranted to establish specific PPG thresholds and further investigate its potential in identifying vulnerable plaques and guiding treatment decisions.

Vascular Remodeling in Coronary Microvascular Dysfunction.

BACKGROUND: Approximately half of the patients with angina and nonobstructive coronary artery disease (ANOCA) have evidence of coronary microvascular dysfunction (CMD). OBJECTIVES: This study aims to characterize patients with ANOCA by measuring their minimal microvascular resistance and to examine the pattern of vascular remodeling associated with these measurements. METHODS: The authors prospectively included patients with ANOCA undergoing continuous thermodilution assessment. Lumen volume and vessel-specific myocardial mass were quantified using coronary computed tomography angiography (CTA). CMD was defined as coronary flow reserve <2.5 and high minimal microvascular resistance as >470 WU. RESULTS: A total of 153 patients were evaluated; 68 had CMD, and 22 of them showed high microvascular resistance. In patients with CMD, coronary flow reserve was 1.9 ± 0.38 vs 3.2 ± 0.81 in controls (P < 0.001). Lumen volume was significantly correlated with minimal microvascular resistance (r = -0.59 [95% CI: -0.45 to -0.71]; P < 0.001). In patients with CMD and high microvascular resistance, lumen volume was 40% smaller than in controls (512.8 ± 130.3 mm3 vs 853.2 ± 341.2 mm3; P < 0.001). Epicardial lumen volume assessed by coronary CTA was independently associated with minimal microvascular resistance (P < 0.001). The predictive capacity of lumen volume from coronary CTA for detecting high microvascular resistance showed an area under the curve of 0.79 (95% CI: 0.69-0.88). CONCLUSIONS: Patients with CMD and high minimal microvascular resistance have smaller epicardial vessels than those without CMD. Coronary CTA detected high minimal microvascular resistance with very good diagnostic capacity. Coronary CTA could potentially aid in the diagnostic pathway for patients with ANOCA.

Predictors for Vulnerable Plaque in Functionally Significant Lesions.

BACKGROUND: Vulnerable plaque presents prognostic implications in addition to functional significance. OBJECTIVES: The aim of this study was to identify relevant features of vulnerable plaque in functionally significant lesions. METHODS: In this multicenter, prospective study conducted across 5 countries, including patients who had invasive fractional flow reserve (FFR) ≤0.80, a total of 95 patients with available pullback pressure gradient (PPG) and plaque analysis on coronary computed tomographic angiography and optical coherence tomography were analyzed. Vulnerable plaque was defined as the presence of plaque rupture or thin-cap fibroatheroma on optical coherence tomography. Among the 25 clinical characteristics, invasive angiographic findings, physiological indexes, and coronary computed tomographic angiographic findings, significant predictors of vulnerable plaque were identified. RESULTS: Mean percentage diameter stenosis, FFR, and PPG were 77.8% ± 14.6%, 0.66 ± 0.13, and 0.65 ± 0.13, respectively. Vulnerable plaque was present in 53 lesions (55.8%). PPG and FFR were identified as significant predictors of vulnerable plaque (P < 0.05 for all). PPG >0.65 and FFR ≤0.70 were significantly related to a higher probability of vulnerable plaque after adjustment for each other (OR: 6.75 [95% CI: 2.39-19.1]; P < 0.001] for PPG >0.65; OR: 4.61 [95% CI: 1.66-12.8]; P = 0.003 for FFR ≤0.70). When categorizing lesions according to combined PPG >0.65 and FFR ≤0.70, the prevalence of vulnerable plaque was 20.0%, 57.1%, 66.7%, and 88.2% in the order of PPG ≤0.65 and FFR >0.70, PPG ≤0.65 and FFR ≤0.70, PPG >0.65 and FFR >0.70, and PPG >0.65 and FFR ≤0.70 (P for trend < 0.001), respectively. CONCLUSIONS: Among low-FFR lesions, the presence of vulnerable plaque can be predicted by PPG combined with FFR without additional anatomical or plaque characteristics. (Precise Percutaneous Coronary Intervention Plan [P3] Study; NCT03782688).

Validation of virtual fractional flow reserve pullback curves.

BACKGROUND: Angiography-derived fractional flow reserve (virtual FFR) has shown excellent diagnostic performance compared with wire-based FFR. However, virtual FFR pullback curves have not been validated yet. OBJECTIVES: To validate the accuracy of virtual FFR pullback curves compared to wire-based FFR pullbacks and to assess their clinical utility using patient-reported outcomes. METHODS: Pooled analysis of two prospective studies, including patients with hemodynamically significant (FFR ≤ 0.80) coronary artery disease (CAD). Virtual and wire-based FFR pullbacks were compared to assess the accuracy of virtual pullbacks to characterize CAD as focal or diffuse. Pullbacks were analyzed visually and quantitatively using the pullback pressure gradient (PPG). Patients underwent PCI, and the Seattle Angina Questionnaire (SAQ) was administered at 3-month follow-up. RESULTS: A total of 298 patients (300 vessels) with both virtual and wire-based pullbacks who underwent PCI were included in the analysis. The mean age was 61.8 ± 8.8, and 15% were female. The agreement on the visual adjudication of the CAD pattern was fair (Cohen's Kappa: 0.31, 95% confidence interval: 0.18-0.45). The mean PPG were 0.65 ± 0.18 from virtual pullbacks and 0.65 ± 0.13 from wire-based pullbacks (r = 0.68, mean difference 0, limits of agreement -0.27 to 0.28). At follow-up, patients with high virtual PPG (>0.67) had higher SAQ angina frequency scores (i.e., less angina) than those with low virtual PPG (SAQ scores 92.0 ± 14.3 vs. 85.5 ± 23.1, p = 0.022). CONCLUSION: Virtual FFR pullback curves showed moderate agreement with wire-based FFR pullbacks. Nonetheless, patients with focal disease based on virtual PPG reported greater improvement in angina after PCI.

A Systematic Approach to the Evaluation of the Coronary Microcirculation Using Bolus Thermodilution: CATH CMD.

Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.

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

BACKGROUND: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease 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 revascularization and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI. RESULTS: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 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 predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P<0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 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 with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97]). CONCLUSIONS: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317.

Effect of Empagliflozin with or without the Addition of Evolocumab on HDL Subspecies in Individuals with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the EXCEED-BHS3 Trial.

Evolocumab and empagliflozin yield a modest rise in plasma high-density lipoprotein cholesterol (HDL-C) through unknown mechanisms. This study aims to assess the effect of evolocumab plus empagliflozin vs. empagliflozin alone on HDL subspecies isolated from individuals with type 2 diabetes mellitus (T2D). This post hoc prespecified analysis of the EXCEED-BHS3 trial compared the effects of a 16-week therapy with empagliflozin (E) alone or in combination with evolocumab (EE) on the lipid profile and cholesterol content in HDL subspecies in individuals with T2D divided equally into two groups of 55 patients. Both treatments modestly increased HDL-C. The cholesterol content in HDL subspecies 2a (7.3%), 3a (7.2%) and 3c (15%) increased from baseline in the E group, while the EE group presented an increase from baseline in 3a (9.3%), 3b (16%) and 3c (25%). The increase in HDL 3b and 3c was higher in the EE group when compared to the E group (p < 0.05). No significant interactive association was observed between changes in hematocrit and HDL-C levels after treatment. Over a 16-week period, empagliflozin with or without the addition of evolocumab led to a modest but significant increase in HDL-C. The rise in smaller-sized HDL particles was heterogeneous amongst the treatment combinations.

Association Between Automated 3D Measurement of Coronary Luminal Narrowing and Risk of Future Myocardial Infarction.

This study focuses on identifying anatomical markers with predictive capacity for long-term myocardial infarction (MI) in focal coronary artery disease (CAD). Eighty future culprit lesions (FCL) and 108 non-culprit lesions (NCL) from 80 patients underwent 3D quantitative coronary angiography. The minimum lumen area (MLA), minimum lumen ratio (MLR), and vessel fractional flow reserve (vFFR) were evaluated. MLR was defined as the ratio between MLA and the cross-sectional area at the proximal lesion edge, with lower values indicating more abrupt luminal narrowing. Significant differences were observed between FCL and NCL in MLR (0.41 vs. 0.53, p < 0.001). MLR correlated inversely with translesional vFFR (r = - 0.26, p = 0.0004) and was the strongest predictor of MI at 5 years (AUC = 0.75). Lesions with MLR < 0.40 had a fourfold increased MI incidence at 5 years. MLR is a robust predictor of future adverse coronary events.

Assessing the Impact of Prolonged Averaging of Coronary Continuous Thermodilution Traces.

Continuous Thermodilution is a novel method of quantifying coronary flow (Q) in mL/min. To account for variability of Q within the cardiac cycle, the trace is smoothened with a 2 s moving average filter. This can sometimes be ineffective due to significant heart rate variability, ventricular extrasystoles, and deep inspiration, resulting in a fluctuating temperature trace and ambiguity in the location of the "steady state". This study aims to assess whether a longer moving average filter would smoothen any fluctuations within the continuous thermodilution traces resulting in improved interpretability and reproducibility on a test-retest basis. Patients with ANOCA underwent repeat continuous thermodilution measurements. Analysis of traces were performed at averages of 10, 15, and 20 s to determine the maximum acceptable average. The maximum acceptable average was subsequently applied as a moving average filter and the traces were re-analysed to assess the practical consequences of a longer moving average. Reproducibility was then assessed and compared to a 2 s moving average. Of the averages tested, only 10 s met the criteria for acceptance. When the data was reanalysed with a 10 s moving average filter, there was no significant improvement in reproducibility, however, it resulted in a 12% diagnostic mismatch. Applying a longer moving average filter to continuous thermodilution data does not improve reproducibility. Furthermore, it results in a loss of fidelity on the traces, and a 12% diagnostic mismatch. Overall, current practice should be maintained.

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.

Influence of intracoronary hemodynamic forces on atherosclerotic plaque phenotypes.

BACKGROUND AND AIMS: Coronary hemodynamics impact coronary plaque progression and destabilization. The aim of the present study was to establish the association between focal vs. diffuse intracoronary pressure gradients and wall shear stress (WSS) patterns with atherosclerotic plaque composition. METHODS: Prospective, international, single-arm study of patients with chronic coronary syndromes and hemodynamic significant lesions (fractional flow reserve [FFR] ≤ 0.80). Motorized FFR pullback pressure gradient (PPG), optical coherence tomography (OCT), and time-average WSS (TAWSS) and topological shear variation index (TSVI) derived from three-dimensional angiography were obtained. RESULTS: One hundred five vessels (median FFR 0.70 [Interquartile range (IQR) 0.56-0.77]) had combined PPG and WSS analyses. TSVI was correlated with PPG (r = 0.47, [95% Confidence Interval (95% CI) 0.30-0.65], p < 0.001). Vessels with a focal CAD (PPG above the median value of 0.67) had significantly higher TAWSS (14.8 [IQR 8.6-24.3] vs. 7.03 [4.8-11.7] Pa, p < 0.001) and TSVI (163.9 [117.6-249.2] vs. 76.8 [23.1-140.9] m-1, p < 0.001). In the 51 vessels with baseline OCT, TSVI was associated with plaque rupture (OR 1.01 [1.00-1.02], p = 0.024), PPG with the extension of lipids (OR 7.78 [6.19-9.77], p = 0.003), with the presence of thin-cap fibroatheroma (OR 2.85 [1.11-7.83], p = 0.024) and plaque rupture (OR 4.94 [1.82 to 13.47], p = 0.002). CONCLUSIONS: Focal and diffuse coronary artery disease, defined using coronary physiology, are associated with differential WSS profiles. Pullback pressure gradients and WSS profiles are associated with atherosclerotic plaque phenotypes. Focal disease (as identified by high PPG) and high TSVI are associated with high-risk plaque features. CLINICAL TRIAL REGISTRATION: https://clinicaltrials,gov/ct2/show/NCT03782688.

Continuous vs Bolus Thermodilution to Assess Microvascular Resistance Reserve.

BACKGROUND: Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) can, in principle, be derived by any method assessing coronary flow. OBJECTIVES: The aim of this study was to compare CFR and MRR as derived by continuous (CFRcont and MRRcont) and bolus thermodilution (CFRbolus and MRRbolus). METHODS: A total of 175 patients with chest pain and nonobstructive coronary artery disease were studied. Bolus and continuous thermodilution measurements were performed in the left anterior descending coronary artery. MRR was calculated as the ratio of CFR to fractional flow reserve and corrected for changes in systemic pressure. In 102 patients, bolus and continuous thermodilution measurements were performed in duplicate to assess test-retest reliability. RESULTS: Mean CFRbolus was higher than CFRcont (3.47 ± 1.42 and 2.67 ± 0.81 [P < 0.001], mean difference 0.80, upper limit of agreement 3.92, lower limit of agreement -2.32). Mean MRRbolus was also higher than MRRcont (4.40 ± 1.99 and 3.22 ± 1.02 [P < 0.001], mean difference 1.2, upper limit of agreement 5.08, lower limit of agreement -2.71). The correlation between CFR and MRR values obtained using both methods was significant but weak (CFR, r = 0.28 [95% CI: 0.14-0.41]; MRR, r = 0.26 [95% CI: 0.16-0.39]; P < 0.001 for both). The precision of both CFR and MRR was higher when assessed using continuous thermodilution compared with bolus thermodilution (repeatability coefficients of 0.89 and 2.79 for CFRcont and CFRbolus, respectively, and 1.01 and 3.05 for MRRcont and MRRbolus, respectively). CONCLUSIONS: Compared with bolus thermodilution, continuous thermodilution yields lower values of CFR and MRR accompanied by an almost 3-fold reduction of the variability in the measured results.

Impact of Post-PCI FFR Stratified by Coronary Artery.

BACKGROUND: Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated. OBJECTIVES: This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery. METHODS: We performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. RESULTS: Overall, 3,336 vessels (n = 2,760 patients) with post-PCI FFR measurements were included in 9 studies. The weighted mean post-PCI FFR was 0.89 (95% CI: 0.87-0.90) and differed significantly between coronary vessels (LAD = 0.86; 95% CI: 0.85 to 0.88 vs non-LAD = 0.93; 95% CI: 0.91-0.94; P < 0.001). Post-PCI FFR was an independent predictor of TVF, with its risk increasing by 52% for every reduction of 0.10 FFR units, and this was mainly driven by TVR. The predictive capacity for TVF was poor for LAD arteries (AUC: 0.52; 95% CI: 0.47-0.58) and moderate for non-LAD arteries (AUC: 0.66; 95% CI: 0.59-0.73; LAD vs non-LAD arteries, P = 0.005). CONCLUSIONS: The LAD is associated with a lower post-PCI FFR than non-LAD arteries, emphasizing the importance of interpreting post-PCI FFR on a vessel-specific basis. Although a higher post-PCI FFR was associated with improved prognosis, its predictive capacity for events differs between the LAD and non-LAD arteries, being poor in the LAD and moderate in the non-LAD vessels.

Fractional Flow Reserve-Guided Stent Optimisation in Focal and Diffuse Coronary Artery Disease.

Assessing coronary physiology after stent implantation facilitates the optimisation of percutaneous coronary intervention (PCI). Coronary artery disease (CAD) patterns can be characterised by the pullback pressure gradient (PPG) index. The impact of focal vs. diffuse disease on physiology-guided incremental optimisation strategy (PIOS) is unknown. This is a sub-study of the TARGET-FFR randomized clinical trial (NCT03259815). The study protocol directed that optimisation be attempted for patients in the PIOS arm when post-PCI FFR was <0.90. Overall, 114 patients (n = 61 PIOS and 53 controls) with both pre-PCI fractional flow reserve (FFR) pullbacks and post-PCI FFR were included. A PPG ≥ 0.74 defined focal CAD. The PPG correlated significantly with post-PCI FFR (r = 0.43; 95% CI 0.26 to 0.57; p-value < 0.001) and normalised delta FFR (r = 0.49; 95% CI 0.34 to 0.62; p-value < 0.001). PIOS was more frequently applied to vessels with diffuse CAD (6% focal vs. 42% diffuse; p-value = 0.006). In patients randomized to PIOS, those with focal disease achieved higher post-PCI FFR than patients with diffuse CAD (0.93 ± 0.05 vs. 0.83 ± 0.07, p < 0.001). There was a significant interaction between CAD patterns and the randomisation arm for post-PCI FFR (p-value for interaction = 0.004). Physiology-guided stent optimisation was applied more frequently to vessels with diffuse disease; however, patients with focal CAD at baseline achieved higher post-PCI FFR.

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.

Coronary Atherosclerosis Phenotypes in Focal and Diffuse Disease.

BACKGROUND: The interplay between coronary hemodynamics and plaque characteristics remains poorly understood. OBJECTIVES: The aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics. METHODS: This multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value. RESULTS: A total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87). CONCLUSIONS: Atherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688).

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.

Diagnostic and Prognostic Role of Cardiac Magnetic Resonance in MINOCA: Systematic Review and Meta-Analysis.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is common in current clinical practice. Cardiac magnetic resonance (CMR) plays an important role in its management and is increasingly recommended by all the current guidelines. However, the prognostic value of CMR in patients with MINOCA is still undetermined. OBJECTIVES: The purpose of this study was to determine the diagnostic and prognostic value of CMR in the management of patients with MINOCA. METHODS: A systematic review was performed to identify studies reporting the results of CMR findings in patients with MINOCA. Random effects models were used to determine the prevalence of different disease entities: myocarditis, myocardial infarction (MI), or takotsubo syndrome. Pooled odds ratios (ORs) and 95% CIs were calculated to evaluate the prognostic value of CMR diagnosis in the subgroup of studies that reported clinical outcomes. RESULTS: A total of 26 studies comprising 3,624 patients were included. The mean age was 54.2 ± 5.3 years, and 56% were men. MINOCA was confirmed in only 22% (95% CI: 0.17-0.26) of the cases and 68% of patients with initial MINOCA were reclassified after the CMR assessment. The pooled prevalence of myocarditis was 31% (95% CI: 0.25-0.39), and takotsubo syndrome 10% (95% CI: 0.06-0.12). In a subgroup analysis of 5 studies (770 patients) that reported clinical outcomes, CMR diagnosis of confirmed MI was associated with an increased risk of major adverse cardiovascular events (pooled OR: 2.40; 95% CI: 1.60-3.59). CONCLUSIONS: In patients with MINOCA, CMR has been demonstrated to add an important diagnostic and prognostic value, proving to be crucial for the diagnosis of this condition. Sixty-eight percent of patients with initial MINOCA were reclassified after the CMR evaluation. CMR-confirmed diagnosis of MINOCA was associated with an increased risk of major adverse cardiovascular events at follow-up.

Ambulatory pulmonary vein isolation workflow using the Perclose ProglideTM suture-mediated vascular closure device: the PRO-PVI study.

AIMS: The leading reason for delayed discharge after pulmonary vein isolation (PVI) is vascular complications. This study aimed to evaluate feasibility, safety, and efficacy of the Perclose Proglide™ suture-mediated vascular closure in ambulatory PVI, report complications, patient satisfaction, and cost of this approach. METHODS AND RESULTS: Patients scheduled for PVI were enrolled prospectively in an observational design. Feasibility was assessed as % discharged the day of procedure. Efficacy was analysed as acute access site closure rate, time to reach haemostasis, time to ambulate, and time to discharge. Safety analysis consisted of vascular complications at 30 days. Cost analysis was reported using direct and indirect cost analysis. A 1:1 propensity matched control cohort was used for comparing time to discharge to usual workflow. Of 50 enrolled patients, 96% were discharged on the same day. 100% of devices were successfully deployed. Immediate (<1 min) haemostasis was reached in 30 patients (62.5%). Mean time to discharge was 5:48 ± 1:03 h (vs. 10:16 ± 1:21 h in the matched cohort, P < 0.0001). Patients reported high level of satisfaction with the post-operative time. No major vascular complication occurred. Cost analysis showed a neutral impact compared to the standard of care. CONCLUSION: The use of the closure device for femoral venous access after PVI led to safe discharge of patients within 6 h from the intervention in 96% of the population. This approach could minimize the overcrowding of healthcare facilities. The gain in post-operative recovery time improved patients' satisfaction and balanced the economic cost of the device.