Fractional flow reserve or 3D-quantitative-coronary-angiography based vessel-FFR guided revascularization. Rationale and study design of the prospective randomized fast III trial.

BACKGROUND: Physiological assessment of intermediate coronary lesions to guide coronary revascularization is currently recommended by international guidelines. Vessel fractional flow reserve (vFFR) has emerged as a new approach to derive fractional flow reserve (FFR) from 3D-quantitative coronary angiography (3D-QCA) without the need for hyperemic agents or pressure wires. STUDY DESIGN AND OBJECTIVES: The FAST III is an investigator-initiated, open label, multicenter randomized trial comparing vFFR guided versus FFR guided coronary revascularization in approximately 2228 patients with intermediate coronary lesions (defined as 30%-80% stenosis by visual assessment or QCA). Intermediate lesions are physiologically assessed using on-line vFFR or FFR and treated if vFFR or FFR ≤0.80. The primary end point is a composite of all-cause death, any myocardial infarction, or any revascularization at 1-year post-randomization. Secondary end points include the individual components of the primary end point and cost-effectiveness will be investigated. CONCLUSIONS: FAST III is the first randomized trial to explore whether a vFFR guided revascularization strategy is non-inferior to an FFR guided strategy in terms of clinical outcomes at 1-year follow-up in patients with intermediate coronary artery lesions.

Clinical Outcome of FFR-Guided Revascularization Strategy of Coronary Lesions: The HALE-BOPP Study.

Background: Recently, questions around the efficacy and effectiveness of Fractional Flow Reserve (FFR) have arisen in various clinical settings. Methods: The Clinical Outcome of FFR-guided Revascularization Strategy of Coronary Lesions (HALE-BOPP) study is an investigator-initiated, multicentre, international prospective study enrolling patients who underwent FFR measurement on at least one vessel. In accordance with the decision-making workflow and treatment, the vessels were classified in three subgroups: (i) angio-revascularized, (ii) FFR-revascularized, (iii) FFR-deferred. The primary endpoint was the occurrence of target vessel failure (TVF, cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization). The analysis was carried out at vessel- and patient-level. Results: 1305 patients with 2422 diseased vessels fulfilled the criteria for the present analysis. Wire-related pitfalls and transient adenosine-related side effects occurred in 0.8% (95% CI: 0.4%-1.4%) and 3.3% (95% CI: 2.5%-4.3%) of cases, respectively. In FFR-deferred vessels, the overall incidence rate of TVF was 0.024 (95% CI: 0.019-0.031) lesion/year. After a median follow-up of 3.6 years, the occurrence of TVF was 6%, 7% and 11.7% in FFR-deferred, FFR-revascularized and angio-revascularized vessels, respectively. Compared to angio-revascularized vessels, FFR-guided vessels (both FFR-revascularized and FFR-deferred vessels) showed a lower TVF incidence rate lesion/year (0.029, 95% CI: 0.024-0.034 vs. 0.049, 95% CI: 0.040-0.061 respectively, p = 0.0001). The result was consistent after correction for confounding factors and across subgroups of clinical interest. The patient-level analysis confirmed the lower occurrence of TVF in negative-FFR vs. positive-FFR subgroups. Conclusions: In a large prospective observational study, an FFR-based strategy for the deferral of coronary lesions is a reliable and safe tool, associated with good outcomes. Clinical Trial Registration: NCT03079739.

Optical coherence tomography-derived predictors of stent expansion in calcified lesions.

BACKGROUND: Severe coronary artery calcification is associated with stent underexpansion and subsequent stent failure. AIMS: We aimed to identify optical coherence tomography (OCT)-derived predictors of absolute (minimal stent area [MSA]) and relative stent expansion in calcified lesions. METHODS: This retrospective cohort study included patients who underwent percutaneous coronary intervention (PCI) with OCT assessment before and after stent implantation between May 2008 and April 2022. Pre-PCI OCT was used to assess calcium burden and post-PCI OCT was used to assess absolute and relative stent expansion. RESULTS: A total of 361 lesions in 336 patients were analyzed. Target lesion calcification (defined as OCT-detected maximum calcium angle ≥ 30°) was present in 242 (67.0%) lesions. Following PCI, median MSA was 5.37 mm2 in calcified lesions and 6.24 mm2 in noncalcified lesions (p < 0.001). Median stent expansion was 78% in calcified lesions and 83% in noncalcified lesions (p = 0.325). In the subset of calcified lesions, average stent diameter, preprocedural minimal lumen area, and total calcium length were independent predictors of MSA in multivariable analysis (mean difference 2.69 mm2 /mm2 , 0.52 mm2 /mm, and -0.28 mm2 /5 mm, respectively, all p < 0.001). Total stent length was the only independent predictor of relative stent expansion (mean difference -0.465% per mm, p < 0.001). Calcium angle, thickness, and the presence of nodular calcification were not significantly associated with MSA or stent expansion in multivariable analyses. CONCLUSION: Calcium length appeared to be the most important OCT-derived predictor of MSA, whereas stent expansion was mainly determined by total stent length.

Culprit lesion plaque characterization and thrombus grading by high-definition intravascular ultrasound in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Dedicated prospective studies investigating high-definition intravascular ultrasound (HD-IVUS)-guided primary percutaneous coronary intervention (PCI) are lacking. The aim of this study was to qualify and quantify culprit lesion plaque characteristics and thrombus using HD-IVUS in patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: The SPECTRUM study is a prospective, single-center, observational cohort study investigating the impact of HD-IVUS-guided primary PCI in 200 STEMI patients (NCT05007535). The first 100 study patients with a de novo culprit lesion and a per-protocol mandated preintervention pullback directly after vessel wiring were subject to a predefined imaging analysis. Culprit lesion plaque characteristics and different thrombus types were assessed. An IVUS-derived thrombus score, including a 1-point adjudication for a long total thrombus length, long occlusive thrombus length, and large maximum thrombus angle, was developed to differentiate between low (0-1 points) and high (2-3 points) thrombus burden. Optimal cut-off values were obtained using receiver operating characteristic curves. RESULTS: The mean age was 63.5 (±12.1) years and 69 (69.0%) patients were male. The median culprit lesion length was 33.5 (22.8-38.9) mm. Plaque rupture and convex calcium were appreciated in 48 (48.0%) and 10 (10.0%) patients, respectively. Thrombus was observed in 91 (91.0%) patients (acute thrombus 3.3%; subacute thrombus 100.0%; organized thrombus 22.0%). High IVUS-derived thrombus burden was present in 37/91 (40.7%) patients and was associated with higher rates of impaired final thrombolysis in myocardial infarction flow (grade 0-2) (27.0% vs. 1.9%, p < 0.001). CONCLUSIONS: HD-IVUS in patients presenting with STEMI allows detailed culprit lesion plaque characterization and thrombus grading that may guide tailored PCI.

Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

Diagnostic accuracy of angiography-based vessel fractional flow reserve after chronic coronary total occlusion recanalization.

BACKGROUND: Angiography-based vessel fractional flow reserve (vFFR) demonstrated a strong correlation with invasive fractional flow reserve (FFR) in both a pre- and post-percutaneous coronary intervention (PCI) setting. However, the role of vFFR and its correlation with post-PCI FFR in chronic coronary occlusions (CTO) has not been evaluated yet. We sought to investigate the diagnostic performance of post-PCI vFFR with post-PCI FFR as a reference in patients undergoing successful CTO PCI. METHODS: Between March 2016 and April 2020, a total of 80 patients from the FFR-SEARCH (prospective registry) and FFR REACT (randomized controlled trial) studies underwent successful CTO recanalization with post-PCI FFR measurements. RESULTS: A total of 50 patients (median age 66 (interquartile range [IQR]: 56-74) years, 76% were male) were eligible for the analysis. Median post-PCI FFR was 0.89 (IQR: 0.84-0.94), while median post-PCI vFFR was 0.91 (IQR: 0.85-0.94) (p 0.10). Suboptimal physiological results, defined as FFR and vFFR <0.90, were identified in 26 (52%) and in 21 (42%) patients, respectively. A strong correlation (r = 0.82) was found between vFFR and FFR with a mean bias of 0.013 ± 0.051. Receiver-operating characteristics curve analysis revealed an excellent accuracy of vFFR in predicting FFR <0.90 (area under the curve: 0.97; 95% confidence interval: 0.93-1.00). CONCLUSION: Post-PCI vFFR shows a good correlation with post-PCI FFR and a high diagnostic accuracy for post-PCI FFR ≤0.90 in patients undergoing successful PCI of a CTO lesion.

Angio-Based Fractional Flow Reserve, Functional Pattern of Coronary Artery Disease, and Prediction of Percutaneous Coronary Intervention Result: a Proof-of-Concept Study.

PURPOSE: Wire-based coronary physiology pullback performed before percutaneous coronary intervention (PCI) discriminates coronary artery disease (CAD) distribution and extent, and is able to predict functional PCI result. No research investigated if quantitative flow ratio (QFR)-based physiology assessment is able to provide similar information. METHODS: In 111 patients (120 vessels) treated with PCI, QFR was measured both before and after PCI. Pre-PCI QFR trace was used to discriminate functional patterns of CAD (focal, serial lesions, diffuse disease, combination). Functional CAD patterns were identified analyzing changes in the QFR virtual pullback trace (qualitative method) or after computation of the QFR virtual pullback index (QVPindex) (quantitative method). QVPindex calculation was based on the maximal QFR drop over 20 mm and the length of epicardial coronary segment with QFR most relevant drop. Then, the ability of the different functional patterns of CAD to predict post-PCI QFR value was tested. RESULTS: By qualitative method, 51 (43%), 20 (17%), 15 (12%), and 34 (28%) vessels were classified as focal, serial focal lesions, diffuse disease, and combination, respectively. QVPindex values >0.71 and ≤0.51 predicted focal and diffuse patterns, respectively. Suboptimal PCI result (post-PCI QFR value ≤0.89) was present in 22 (18%) vessels. Its occurrence differed across functional patterns of CAD (focal 8% vs. serial lesions 15% vs. diffuse disease 33% vs. combination 29%, p=0.03). Similarly, QVPindex was correlated with post-PCI QFR value (r=0.62, 95% CI 0.50-0.72). CONCLUSION: Our results suggest that functional patterns of CAD based on pre-PCI QFR trace can predict the functional outcome after PCI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02811796. Date of registration: June 23, 2016.

Angiography-Based Fractional Flow Reserve: State of the Art.

PURPOSE OF REVIEW: Three-dimensional quantitative coronary angiography-based methods of fractional flow reserve (FFR) derivation have emerged as an appealing alternative to conventional pressure-wire-based physiological lesion assessment and have the potential to further extend the use of physiology in general. Here, we summarize the current evidence related to angiography-based FFR and perspectives on future developments. RECENT FINDINGS: Growing evidence suggests good diagnostic performance of angiography-based FFR measurements, both in chronic and acute coronary syndromes, as well as in specific lesion subsets, such as long and calcified lesions, left main coronary stenosis, and bifurcations. More recently, promising results on the superiority of angiography-based FFR as compared to angiography-guided PCI have been published. Currently available angiography -FFR indices proved to be an excellent alternative to invasive pressure wire-based FFR. Dedicated prospective outcome data comparing these indices to routine guideline recommended PCI including the use of FFR are eagerly awaited.

Comparison of quantitative flow ratio, Pd/Pa and diastolic hyperemia-free ratio versus fractional flow reserve in non-culprit lesion of patients with non ST-segment elevation myocardial infarction.

OBJECTIVES: To investigate the correlation between quantitative flow ratio (QFR), Pd/Pa, diastolic hyperemia-free ratio (DFR) and fractional flow reserve (FFR, gold standard) in non-culprit lesion (NCL) of patients with non ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: The non-hyperemic pressure ratio (NHPR) and the angiography-based indexes have been developed to overcome the limitation of the use of the FFR. METHODS: Between January and December 2019, 184 NCL from 116 NSTEMI patients underwent physiologic assessment and were included in the study. NCLs were investigated with QFR, Pd/Pa, DFR, and FFR. Mean values of QFR, Pd/Pa, DFR and FFR were 0.85 ± 0.10, 0.92 ± 0.07, 0.93 ± 0.05 and 0.84 ± 0.07, respectively. RESULTS: DFR and FFR showed a good correlation (r = 0.76). Bland and Altman plot showed a mean difference of 0.080. DFR Diagnostic accuracy was 88%. The area under the ROC curve (AUC) for DFR was 0.946 (95%CI 0.90-0.97, p = .0001). Similar findings were reported for Pd/Pa (r = 0.73; mean difference 0.095, diagnostic accuracy 84%, AUC 0.909 [95%CI 0.85-0.94, p = .0001]) and QFR (r = 0.68; mean difference 0.01; diagnostic accuracy 88%, AUC 0.964 [95% CI 0.91-0.98, p = .0001]). FFR, QFR, Pd/Pa and DFR identified 31%, 32%, 30% and 32% potentially flow-limiting lesions, respectively. CONCLUSIONS: In NSTEMI patients, QFR, Pd/Pa and DFR showed equivalence as compared to gold standard FFR in the discrimination of non-culprit lesions requiring revascularization.

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

BACKGROUND: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. METHODS: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

Ticagrelor Increases SIRT1 and HES1 mRNA Levels in Peripheral Blood Cells from Patients with Stable Coronary Artery Disease and Chronic Obstructive Pulmonary Disease.

Ticagrelor is a powerful P2Y12 inhibitor with pleiotropic effects in the cardiovascular system. Consistently, we have reported that in patients with stable coronary artery disease (CAD) and concomitant chronic obstructive pulmonary disease (COPD) who underwent percutaneous coronary intervention (PCI), 1-month treatment with ticagrelor was superior in improving biological markers of endothelial function, compared with clopidogrel. The objective of this study was to investigate the mechanisms underlying these beneficial effects of ticagrelor by conducting molecular analyses of RNA isolated from peripheral blood cells of these patients. We determined mRNAs levels of markers of inflammation and oxidative stress, such as RORγt (T helper 17 cells marker), FoxP3 (regulatory T cells marker), NLRP3, ICAM1, SIRT1, Notch ligands JAG1 and DLL4, and HES1, a Notch target gene. We found that 1-month treatment with ticagrelor, but not clopidogrel, led to increased levels of SIRT1 and HES1 mRNAs. In patients treated with ticagrelor or clopidogrel, we observed a negative correlation among changes in both SIRT1 and HES1 mRNA and serum levels of Epidermal Growth Factor (EGF), a marker of endothelial dysfunction found to be reduced by ticagrelor treatment in our previous study. In conclusion, we report that in stable CAD/COPD patients ticagrelor positively regulates HES1 and SIRT1, two genes playing a protective role in the context of inflammation and oxidative stress. Our observations confirm and expand previous studies showing that the beneficial effects of ticagrelor in stable CAD/COPD patients may be, at least in part, mediated by its capacity to reduce systemic inflammation and oxidative stress.

Systematic Review Article: New Drug Strategies for Treating Resistant Hypertension-the Importance of a Mechanistic, Personalized Approach.

Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events. Hypertension guidelines proposed a triple combination therapy based on renin angiotensin system blocking agent, a thiazide or thiazide-like diuretic, and a dihydropyridinic calcium-channel blocker, to almost all patients with RHT, who should also receive either a beta-blocker or a mineralocorticoid receptor antagonist, or both, depending on concomitant conditions and contraindications. Several other drugs may be attempted, when elevated BP levels persist in these RHT patients, although their added efficacy in lowering BP levels on top of optimal medical therapy is uncertain. Also, renal denervation has demonstrated to be a valid therapeutic alternative in RHT patients. More recently, novel drug classes and molecules have been tested in phase 2 randomised controlled clinical trials in patients with RHT on top of optimal medical therapy with at least 2-3 antihypertensive drugs. These novel drugs, which are orally administered and are able to antagonize different pathophysiological pathways, are represented by non-steroid mineralocorticorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin receptor antagonists, all of which have proven to reduce seated office and 24-h ambulatory systolic/diastolic BP levels. The main findings of randomized clinical trials performed with these drugs  as well as their potential indications for the clinical management of RHT patients are summarised in this systematic review article.

Intravascular Imaging-Derived Physiology-Basic Principles and Clinical Application.

Intravascular imaging-derived physiology is emerging as a promising tool allowing simultaneous anatomic and functional lesion assessment. Recently, several optical coherence tomography-based and intravascular ultrasound-based fractional flow reserve (FFR) indices have been developed that compute FFR through computational fluid dynamics, fluid dynamics equations, or machine-learning methods. This review aims to provide an overview of the currently available intravascular imaging-based physiologic indices, their diagnostic performance, and clinical application.

Vessel fractional flow reserve-based non-culprit lesion reclassification in patients with ST-segment elevation myocardial infarction: Impact on treatment strategy and clinical outcome (FAST STEMI I study).

BACKGROUND: Complete revascularization in patients with ST-segment elevation myocardial (STEMI) improves clinical outcome. Vessel fractional flow reserve (vFFR) has been validated as a non-invasive physiological technology to evaluate hemodynamic lesion significance without need for a dedicated pressure wire or hyperemic agent. This study aimed to assess discordance between vFFR reclassification and treatment strategy in intermediate non-culprit lesions of STEMI patients and to assess the clinical impact of this discordance. METHODS: This was a single-center, retrospective cohort study. From January 2018 to December 2019, consecutive eligible STEMI patients were screened based on the presence of a non-culprit vessel with an intermediate lesion (30-80% angiographic stenosis) feasible for offline vFFR analysis. The primary outcome was the percentage of non-culprit vessels with discordance between vFFR and actual treatment strategy. The secondary outcome was two-year vessel-oriented composite endpoint (VOCE), a composite of vessel-related cardiovascular death, vessel-related myocardial infarction, and target vessel revascularization. RESULTS: A total of 441 patients (598 non-culprit vessels) met the inclusion criteria. Median vFFR was 0.85 (0.73-0.91). Revascularization was performed in 34.4% of vessels. Discordance between vFFR and actual treatment strategy occurred in 126 (21.1%) vessels. Freedom from VOCE was higher for concordant vessels (97.5%) as compared to discordant vessels (90.6%)(p = 0.003), particularly due to higher adverse event rates in discordant vessels with a vFFR ≤0.80 but deferred revascularization. CONCLUSIONS: In STEMI patients with multivessel disease, discordance between vFFR reclassification and treatment strategy was observed in 21.1% of non-culprit vessels with an intermediate lesion and was associated with increased vessel-related adverse events.

Association Between 3D-Angiography Based Fractional Flow Reserve and Non-Invasive Myocardial Ischemia Testing: The FAST ISCHEMIA Study.

BACKGROUND: In order to facilitate fractional flow reserve (FFR)-guided lesion assessment, several 3-dimensional (3D)-angiography-based physiological indices have been recently validated. Thus far, limited data are available on the association of these indices with conventional forms of ischemia testing. AIM: The aim of the study was to determine the association between 3D-angiography-based vessel-FFR (vFFR) and myocardial ischemia as assessed by exercise electrocardiography (ECG) testing, dobutamine stress echocardiography, single photon emission computed tomography myocardial perfusion imaging (SPECTMPI), and stress cardiovascular magnetic resonance imaging (stress CMR). METHODS: FAST ISCHEMIA is a retrospective, single-center cohort study including patients who underwent non-invasive myocardial ischemia testing and subsequent coronary angiography (≤3 months). A total of 145 patients (340 vessels) were analyzed. The overall patient-based sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of vFFR ≤0.80 in any vessel for ischemia was 64% (95% confidence interval [CI], 53-74), 71% (95% CI, 54-84), 83% (95% CI, 72-91), 46% (95% CI, 33-60), 2.16 (95% CI, 1.25-3.74), and 0.52 (95% CI, 0.36-0.74), respectively. Multivariable logistic regression showed that vFFR ≤0.80 was significantly associated with ischemia on a patient level (odds ratio, 8.13; 95% CI, 2.51-30.06; P<.001) and on a vascular territory level (odds ratio, 2.75; 95% CI, 1.17-6.44; P<.01). CONCLUSION: Our study suggests that vFFR ≤0.80 has a modest association with non-invasive myocardial ischemia testing using either exercise ECG or stress imaging modalities. After correcting for independent confounders, vFFR was independently associated with ischemia on a non-invasive myocardial ischemia detection test.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Non-ST-Elevation Coronary Syndromes and Multivessel Disease: A Systematic Review and Meta-Analysis.

There is lack of evidence regarding the optimal revascularization strategy in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD). This systematic review and meta-analysis compares the clinical impact of percutaneous coronary intervention (PCI) with that of coronary artery bypass graft surgery (CABG) in this subset of patients. EMBASE, MEDLINE, and Web of Knowledge were searched for studies including patients with NSTE-ACS and MVD who underwent PCI or CABG up to September 1, 2021. The primary end point of the meta-analysis was all-cause mortality at 1 year. The secondary end points were myocardial infarction (MI), stroke, or repeat revascularization at 1 year. The analysis was conducted using the Mantel-Haenszel random-effects model to calculate the odds ratio (OR) with 95% confidence interval (CI). Four prospective observational studies met the inclusion criteria, including 1,542 patients who underwent CABG and 1,630 patients who underwent PCI. No significant differences were found in terms of all-cause mortality (OR 0.91, 95% CI 0.68 to 1.21, p = 0.51), MI (OR 0.78, 95% CI 0.40 to 1.51, p = 0.46), or stroke (OR 1.54, 95% CI 0.55 to 4.35, p = 0.42) between PCI and CABG. Repeat revascularization was significantly lower in the CABG group (OR 0.21, 95% CI 0.13 to 0.34, p <0.00001). In patients presenting with NSTE-ACS and MVD, 1-year mortality, MI, and stroke were similar between patients treated with either PCI or CABG, but the repeat revascularization rate was higher after PCI.

Long Stent Implantation on the Left Anterior Descending Coronary Artery at a Follow-Up of More Than Five Years.

BACKGROUND: Stent implantation represents the standard of care in coronary intervention. While a short stent implanted on a focal lesion located on the left anterior descending artery (LAD) seems a reasonable alternative to an internal mammary implant, the same for long stents is still debated. METHODS: We reported the long-term data of 531 consecutive patients who underwent Percutaneous Coronary Intervention (PCI) with long stents in two highly specialized centres. The main inclusion criteria were the implantation of stents longer than 30 mm on the LAD and a minimum follow-up (FU) of five years. The primary endpoint was mortality, and the secondary endpoints were any myocardial infarction (MI), target vessel and lesion revascularization (TVR and TLR, respectively), and stent thrombosis (ST) observed as definite, probable, or possible. RESULTS: In this selected population with characteristics of complex PCI (99.1%), the long-term follow-up (mean 92.18 ± 35.5 months) estimates of all-cause death, cardiovascular death, and any myocardial infarction were 18.3%, 10.5%, and 9.3%, respectively. Both all-cause and cardiovascular deaths are significantly associated with three-vessel disease (HR 6.8; confidence of interval (CI) 95% 3.844-11.934; p < 0.001, and HR 4.7; CI 95% 2.265-9.835; p < 0.001, respectively). Target lesion (TLR) and target vessel revascularization (TVR) are associated with the presence of three-lesion disease on the LAD (HR 3.4; CI 95% 1.984-5.781; p < 0.001; HR 3.9 CI 95% 2.323-6.442; p < 0.001, respectively). Re-PCI for any cause occurred in 31.5% of patients and shows an increased risk for three-lesion stenting (HR 4.3; CI 95% 2.873-6.376; p < 0.001) and the treatment of bifurcation with two stents (HR 1.6; 95% CI 1.051-2.414; p = 0.028). Stent thrombosis rate at the 5-year FU was 4.4% (1.3% definite; 0.9% probable; 2.1% possible), including a 1.7% rate of very-late thrombosis. The stent length superior to 40 mm was not associated with poor outcomes (all-cause death p = 0.349; cardiovascular death p = 0.855; MI p = 0.691; re-PCI p = 0.234; TLR p = 0.805; TVR p = 0.087; ST p = 0.189). CONCLUSION: At an FU of longer than five years, patients treated with stents longer than 30 mm in their LAD showed acceptable procedural results but poor outcomes.

Validation of Segmental Post-PCI Physiological Gradients With IVUS-Detected Focal Lesions and Stent Underexpansion.

BACKGROUND: Segmental postpercutaneous coronary intervention (PCI) pressure gradients may detect residual disease and potential targets for optimization. However, universal definitions of relevant segmental gradients are lacking. OBJECTIVES: This study sought to evaluate the diagnostic performance of post-PCI fractional flow reserve (FFR), distal coronary pressure-to-aortic pressure ratio (Pd/Pa), and diastolic pressure ratio (dPR) gradients to detect residual focal lesions and stent underexpansion as observed by intravascular ultrasound (IVUS). METHODS: Patients from the IVUS-guided optimization arm of the FFR REACT (FFR-guided PCI Optimization Directed by High-Definition IVUS Versus Standard of Care) trial with complete IVUS and FFR pullback data were included. Patients with angiographically successful PCI and post-PCI FFR <0.90 underwent FFR, Pd/Pa, and IVUS pullbacks. dPR was calculated offline using dedicated software. Segmental pressure gradients (distal, in stent, and proximal) in segments ≥5 mm were evaluated against IVUS-detected residual disease (distal or proximal focal lesions and stent underexpansion). RESULTS: A total of 139 vessels were included (mean post-PCI FFR: 0.83 ± 0.05, range 0.56-0.89). Focal distal and proximal lesions were detected by IVUS in 23 (17.4%) of 132 and 14 (12.6%) of 111 vessels, respectively, whereas stent underexpansion was present in 86 (61.9%) vessels. Diagnostic ability of segmental FFR gradients to predict IVUS-detected distal and proximal lesions was moderate-to-good (area under the curve [AUC]: 0.69 and 0.84, respectively) and poor to moderate for segmental Pd/Pa and dPR gradients (AUC ranging from 0.58 to 0.69). In-stent gradients had no discriminative ability to detect stent underexpansion (FFR AUC: 0.52; Pd/Pa AUC: 0.54; dPR AUC: 0.55). CONCLUSIONS: In patients with post-PCI FFR <0.90, segmental post-PCI pressure gradients have moderate discriminative ability to identify IVUS-detected focal lesions but no discriminative ability to identify IVUS-detected stent underexpansion.

Predictors of discordance between fractional flow reserve (FFR) and diastolic pressure ratio (dPR) in intermediate coronary lesions.

Background: Recently, non-hyperemic pressure ratios (NHPRs) have been validated as a reliable alternative to fractional flow reserve (FFR). However, a discordance between FFR and NHPRs is observed in 20-25% of cases. The aim of this study is to evaluate predictors of discordance between FFR and diastolic Pressure ratio (dPR). Methods: PREDICT is a retrospective, single center, investigator-initiated study including 813 patients (1092vessels) who underwent FFR assessment of intermediate coronary lesions (angiographic 30%-80% stenosis). dPR was calculated using individual pressure waveforms and dedicated software. Clinical, angiographic and hemodynamic variables were compared between patients with concordant and discordant FFR and dPR values. Results: Median age was 65 (IQR:59-73) years and 70% were male. Hemodynamically significant lesions, as defined by FFR ≤ 0.80, and dPR ≤ 0.89, were identified in 29.6% and 30.3% of cases, respectively. Overall, FFR and dPR values were discordant in 22.1% patients (17.4% of the vessels). Discordance was related to FFR+/dPR- and FFR-/dPR + in 11.8% and 10.3% of patients, respectively.In case of FFR-dPR discordance, a higher prevalence of left anterior descending arteries lesions was observed (70.5% vs. 53.1%, p < 0.001) and mean values of both FFR and dPR were significantly lower (FFR 0.81 ± 0.05 vs 0.85 ± 0.08, p < 0.001, and dPR 0.89 ± 0.04 vs 0.92 ± 0.08,p < 0.001) as compared to vessels with FFR and dPR concordance. Following multivariable adjustment, dPR delta (defined as the absolute difference between measured dPR to the cut-off value of 0.89) turned out to be the only independent predictor of discordance (OR = 0.74, 95% CI 0.68-0.79, p < 0.001). Conclusion: Our study suggests that FFR-to-dPR discordance occurs in approximately one-fifth of patients. Absolute dPR delta appears to be the only independent predictor of discordance.

Symptoms-to-emergency-call timing delay in acute coronary syndrome before and during COVID-19: independent predictors and their impact on mortality.

BACKGROUND: The COVID-19 pandemic severely impacted global health. The aim of this study was to compare predictors of symptoms-to-emergency-call timing delay in acute coronary syndrome (ACS) and their impact on mortality before and during the COVID-19 outbreak. METHODS: We collected sociodemographic, clinical data, procedural features, preadmission and intra-hospital outcomes of consecutive patients admitted for ACS in seventeen Italian centers from March to April 2018, 2019, and 2020. RESULTS: In 2020, a 32.92% reduction in ACS admissions was observed compared to 2018 and 2019. Unstable angina, typical and atypical symptoms, and intermittent angina were identified as significant predictors of symptoms-to-emergency-call timing delay before and during the COVID-19 pandemic (P<0.005 for all the items). Differently from 2018-2019, during the pandemic, hypertension and dyspnea (P=0.002 versus P=0.490 and P=0.001 vs. P=0.761 for 2018-2019 and 2020, respectively) did not result as predictors of delay in symptoms-to-emergency-call timing. Among these predictors, only the atypical symptoms (HR 3.36; 95% CI: 1.172-9.667, P=0.024) in 2020 and the dyspnea (HR 2.64; 95% CI: 1.345-5.190, P=0.005) in 2018-2019 resulted significantly associated with higher mortality. Finally, the family attendance at the onset of the symptoms resulted in a reduction in symptoms-to-emergency-call timing (in 2020 P<0.001; CI: -1710.73; -493.19) and in a trend of reduced mortality (HR 0.31; 95% CI: 0.089-1.079, P=0.066) in 2020. CONCLUSIONS: During the COVID-19 outbreak, atypical symptoms and family attendance at ACS onset were identified, respectively, as adverse and favorable predictors of symptoms-to-emergency-call timing delay and mortality.