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Background: The FORZA trial (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) prospectively compared the use of fractional flow reserve (FFR) or optical coherence tomography (OCT) for treatment decisions and percutaneous coronary intervention (PCI) optimization in patients with angiographically intermediate coronary lesions. Murray law-based quantitative-flow-ratio (μQFR) is a novel noninvasive method for the computation of FFR. In the present study, we evaluated the clinical impact of μQFR, FFR, or OCT guidance in FORZA trial lesions at 3-year follow-up., Methods: μQFR was assessed at baseline and, in the case of a decision to intervene, after (FFR- or OCT-guided) PCI. The baseline μQFR was considered the final μQFR for deferred lesions, and post-PCI μQFR value was taken as final for stented lesions. The primary end point was target vessel failure ([TVF]; cardiac death, target-vessel-related myocardial infarction, and target-vessel-revascularization) at a 3-year follow-up., Results: A total of 419 vessels (199 OCT-guided and 220 FFR-guided) were included in the FORZA trial. μQFR was evaluated in 256 deferred lesions and 159 treated lesions (98 OCT-guided PCI and 61 FFR-guided PCI). In treated lesions, post-PCI μQFR was higher in OCT-group compared with FFR-group (median, 0.93 versus 0.91; P =0.023), and the post-PCI μQFR improvement was greater in FFR-group (0.14 versus 0.08; P <0.0001). At 3-year follow-up, OCT- and FFR-guided treatment decisions resulted in comparable TVF rate (6.7% versus 7.9%; P =0.617). Final μQFR was the only predictor of TVF. μQFR ≤0.89 was associated with 3× increase in TVF (11.6% versus 3.7%; P =0.004). PCI was a predictor of higher final μQFR (odds ratio, 0.22 [95% CI, 0.14-0.34]; P <0.001)., Conclusions: In vessels with angiographically intermediate coronary lesions, OCT-guided PCI resulted in comparable clinical outcomes as FFR-guided PCI. μQFR estimated at the end of diagnostic or interventional procedure predicted 3-year TVF., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01824030., Competing Interests: Disclosures Dr Wijns reports institutional research grants and past honoraria from MicroPort; senior advisor of Rede Optimus Research, Corrib Core Laboratory and co-founder of Argonauts, an innovation facilitator. Dr Tu is a co-founder of Pulse Medical and reports research grant and consultancy from Pulse Medical. Drs Burzotta, Trani, and Aurigemma received speaker’s fees from Abbott, Medtronic, Abiomed and Terumo. Dr Leone received speaking honoraria from St. Jude Medical/Abbott, Medtronic, Abiomed and from Bracco Imaging. The other authors report nop conflicts.

Background Myocardial bridging (MB) may represent a cause of myocardial ischemia in patients with non-obstructive coronary artery disease (NOCAD). Herein, we assessed the interplay between MB and coronary vasomotor disorders, also evaluating their prognostic relevance in patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) or stable NOCAD. Methods and Results We prospectively enrolled patients with NOCAD undergoing intracoronary acetylcholine provocative test. The incidence of major adverse cardiac events, defined as the composite of cardiac death, non-fatal myocardial infarction, and rehospitalization for unstable angina, was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires summary score. We enrolled 310 patients (mean age, 60.6±11.9; 136 [43.9%] men; 169 [54.5%] stable NOCAD and 141 [45.5%] MINOCA). MB was found in 53 (17.1%) patients. MB and a positive acetylcholine test coexisted more frequently in patients with MINOCA versus stable NOCAD. MB was an independent predictor of positive acetylcholine test and MINOCA. At follow-up (median, 22 months; interquartile range, 13-32), patients with MB had a higher rate of major adverse cardiac events, mainly driven by a higher rate of hospitalization attributable to angina, and a lower Seattle Angina Questionnaires summary score (all P <0.001) compared with patients without MB. In particular, the group of patients with MB and a positive acetylcholine test had the worst prognosis. Conclusions Among patients with NOCAD, coronary spasm associated with MB may predict a worse clinical presentation with MINOCA and a higher rate of hospitalization attributable to angina at long-term follow-up with a low rate of hard events.

Objective: The objective is to analyze the acute and midterm angiographic outcome of percutaneous treatment of left main coronary stem (LM-PCI) guided by optical coherence tomography (OCT)., Background: LM-PCI is a complex procedure, and several anatomical factors may impair its outcome. Intravascular imaging is emerging as a useful tool to guide the procedure., Methods: We conducted a retrospective analysis of patients undergoing LM-PCI at three European centers between 2014 and 2017 with a control angiography at 6-12 months. Patients were divided into two groups: OCT-guidance (pre- and post-PCI) and control group (standard angiographic guidance with/out intravascular ultrasound [IVUS]). A blinded core lab analyzed all angiographic images. Primary endpoint was late lumen loss (LLL) after 6 months., Results: A total of 112 patients entered the study, 55 in the OCT group and 57 in the control group (10 IVUS). Baseline and procedural characteristics were similar between groups. Overall, reference vessel diameter of the LM was 3.98 ± 0.65 mm. OCT guidance detected four cases of stent underexpansion (7.2%) and six cases of acute malapposition (10.9%). After a median of 207 ± 23 days, LLL of LM tended to be lower in the OCT group (0.12 ± 0.41 vs. 0.26 ± 0.52 mm, p = .10), and was significantly reduced in the distal portion of the main vessel (0.03 ± 0.45 vs. 0.24 ± 0.53 mm, p = .025). Percent diameter stenosis was also lower (14 ± 9 vs. 19 ± 16%, p = .05). Adverse event rates were similar in the two groups., Conclusions: In this study, systematic OCT guidance during LM-PCI allowed a timely detection and correction of acute stent underexpansion and malapposition, and was associated with signs of improved angiographic outcome at midterm, compared to standard practice., (© 2019 Wiley Periodicals, Inc.)

Background: Coronary vasomotor dysfunction represents an important mechanism responsible for myocardial ischaemia in patients with non-obstructive coronary artery disease (CAD). The use of invasive provocative tests allows identifying patients with epicardial or microvascular spasm. Of note, clinical characteristics associated with the occurrence of epicardial or microvascular spasm have still not completely clarified., Methods and Results: We prospectively enrolled consecutive patients undergoing coronary angiography for suspected myocardial ischaemia/necrosis with evidence of non-obstructive CAD and undergoing intracoronary provocative test for suspected vasomotor dysfunction. Patients with a positive provocative test were enrolled. Clinical, echocardiographic and angiographic characteristics of patients were evaluated according to the pattern of vasomotor dysfunction (epicardial vs. microvascular spasm). We included 120 patients [68 patients with stable angina and 52 patients with myocardial infarction and non-obstructive coronary arteries (MINOCA)]. In particular, 77 (64.2%) patients had a provocative test positive for epicardial spasm and 43 (35.8%) patients for microvascular spasm. Patients with epicardial spasm were more frequently males, smokers, had higher rates of diffuse coronary atherosclerosis at angiography and more frequently presented with MINOCA. On the other hand, patients with microvascular spasm presented more frequently diastolic dysfunction. At multivariate logistic regression analysis male sex, smoking, and diffuse coronary atherosclerosis were independent predictors for the occurrence of epicardial spasm., Conclusions: Our study showed that specific clinical features are associated with different responses to intracoronary provocative test. Epicardial spasm is more frequent in males and in MINOCA patients, whereas microvascular spasm is more frequent in patients with stable angina and is associated with diastolic dysfunction.

Objectives: The aim of this study was to investigate the safety and efficacy of coronary protection by preventive coronary wiring and stenting across the coronary ostia in patients at high risk for coronary obstruction after transcatheter aortic valve replacement (TAVR)., Background: Coronary obstruction following TAVR is a life-threatening complication with high procedural and short-term mortality., Methods: Data were collected retrospectively from a multicenter international registry between April 2011 and February 2019., Results: Among 236 patients undergoing coronary protection with preventive coronary wiring, 143 had eventually stents implanted across the coronary ostia after valve deployment. At 3-year follow-up, rates of cardiac death were 7.8% in patients receiving stents and 15.7% in those not receiving stents (adjusted hazard ratio: 0.42; 95% confidence interval: 0.14 to 1.28; p = 0.13). There were 2 definite stent thromboses (0.9%) in patients receiving stents, both occurring after TAVR in "valve-in-valve" procedures. In patients not receiving stents, there were 4 delayed coronary occlusions (DCOs) (4.3%), occurring from 5 min to 6 h after wire removal. Three cases occurred in valve-in-valve procedures and 1 in a native aortic valve procedure. Distance between the virtual transcatheter valve and the protected coronary ostia <4 mm was present in 75.0% of patients with DCO compared with 30.4% of patients without DCO (p = 0.19)., Conclusions: In patients undergoing TAVR at high risk for coronary obstruction, preventive stent implantation across the coronary ostia is associated with good mid-term survival rates and low rates of stent thrombosis. Patients undergoing coronary protection with wire only have a considerable risk for DCO., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The CLIMA study, on the relationship between coronary plaque morphology of the left anterior descending artery and twelve months clinical outcome, was designed to explore the predictive value of multiple high-risk plaque features in the same coronary lesion [minimum lumen area (MLA), fibrous cap thickness (FCT), lipid arc circumferential extension, and presence of optical coherence tomography (OCT)-defined macrophages] as detected by OCT. Composite of cardiac death and target segment myocardial infarction was the primary clinical endpoint., Methods and Results: From January 2013 to December 2016, 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending coronary artery in the context of clinically indicated coronary angiogram were prospectively enrolled at 11 independent centres (clinicaltrial.gov identifier NCT02883088). At 1-year, the primary clinical endpoint was observed in 37 patients (3.7%). In a total of 1776 lipid plaques, presence of MLA <3.5 mm2 [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.1-4.0], FCT <75 µm (HR 4.7, 95% CI 2.4-9.0), lipid arc circumferential extension >180° (HR 2.4, 95% CI 1.2-4.8), and OCT-defined macrophages (HR 2.7, 95% CI 1.2-6.1) were all associated with increased risk of the primary endpoint. The pre-specified combination of plaque features (simultaneous presence of the four OCT criteria in the same plaque) was observed in 18.9% of patients experiencing the primary endpoint and was an independent predictor of events (HR 7.54, 95% CI 3.1-18.6)., Conclusion: The simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The reliability of fractional flow reserve (FFR) in aortic stenosis (AS) has been questioned because of the uncertain response to vasodilators. A retrospective multicenter cohort of 114 AS patients who underwent coronary physiology assessment was compared with 154 controls before and after propensity matching adjustment. The difference between resting distal coronary vs aortic pressure ratio (Pd/Pa) and FFR (ΔPd/Pa-FFR) was tested against the severity of AS. ΔPd/Pa-FFR was not influenced by the severity of AS in terms of aortic valve area (r = - 0.02, p = 0.83) and gradient (r = - 0.05, p = 0.64) or by the left ventricle hypertrophy (r = - 0.03, p = 0.88). Conversely, ΔPd/Pa-FFR was influenced by the presence of diabetes (r = - 0.24, p = 0.005), peripheral vascular disease (r = - 0.16, p = 0.047), and chronic kidney disease (r = - 0.19, p = 0.03). No significant difference was observed in the ΔPd/Pa-FFR between patients with AS and matched controls. Further studies are warranted to validate the FFR-guided revascularization in patients with AS.

Aim: To assess the impact of lesion predilation with kissing inflation using under-sized balloons (pre-kissing [PK]) on the procedural outcome of percutaneous intervention (PCI) on coronary bifurcation lesions (CBLs)., Methods: Patients who underwent PCI with second-generation drug-eluting stenting on a complex CBL (Medina 1,1,1 or 1,0,1 or 0,1,1) were selected. The study population was divided according to the lesion preparation into the PK group and the control group. To adjust for higher anatomic complexity of PK patients, a 2:1 propensity-matched (PM)-control group was selected. The PCI procedural details were assessed to evaluate occurrence of "side-branch trouble" (primary procedural endpoint) after main-vessel (MV) stenting. Angiographic characteristics, including side-branch TIMI flow during PCI, were also systematically evaluated., Results: A total of 538 patients were identified, with 66 patients in the PK group, 472 patients in the control group, and 126 patients in the PM-control group. Side-branch trouble was less common in side-branch PK patients vs the PM-control patients (7.5% vs 18.0%, respectively; P=.03). In multivariable analysis, the absence of PK independently predicted side-branch trouble. Among selected patients with a long side-branch lesion (122 patients), the PK technique improved post-MV stenting side-branch TIMI flow., Conclusions: Use of PK with under-sized balloons may facilitate side-branch management after MV stenting in patients with complex CBL undergoing provisional stenting.

Background: A sizeable proportion of patients with Acute Coronary Syndromes (ACS) shows a unique adaptive immune system profile, associated to a worse outcome, characterized by higher CD4 + CD28 null T-cells, lower regulatory T-cells (Treg) and increased CD4 + CD28 null /Treg ratio. We sought to investigate the correlation between CD4 + CD28 null T-cells, Treg, CD4 + CD28 null /Treg ratio and plaque phenotype as assessed by Optical Coherence Tomography (OCT)., Methods: Peripheral blood mononuclear cells (PBMC) were collected from 30 Non-ST Elevation Myocardial Infarction (NSTEMI) patients, sub-grouped according to OCT analysis of culprit lesions into two cohorts: Ruptured Fibrous Cap (NSTEMI-RFC, n = 12) and Intact Fibrous Cap (NSTEMI-IFC, n = 18). Stable Angina patients (SA, n = 18) were used as controls. We examined the frequency of CD4 + CD28 null and Treg (defined as CD4 + CD25 high CD127 low Foxp3 + T-cells) by flow-cytometry., Results: CD4 + CD28 null frequency (median, range) was significantly higher in NSTEMI-RFC patients (17.3%, 12.5-33.8) as compared with NSTEMI-IFC (3.8%, 0.3-14.1) and SA (3%, 0.6-17.7) (P < 0.001 for all comparisons). We also found a higher CD4 + CD28 null /Treg ratio in NSTEMI-RFC patients (6.6%, 3.7-13.9) than in NSTEMI-IFC (1.6%, 0.3-5.2) and SA (1.2%, 0.3-8.7) (P < 0.001 for all comparisons). Finally, there was an inverse correlation between CD4 + CD28 null /Treg ratio and cap-thickness (R = -0.44; P = 0.002)., Conclusion: Patients with NSTEMI presenting with RFC as culprit lesion at OCT evaluation have a specific perturbation of adaptive immunity, mostly involving CD4 + CD28 null T- cells and Tregs, as compared with patients with IFC and SA. This specific imbalance of T-cells might play a key role in fibrous cap thinning, predisposing atherosclerotic plaque to rupture., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The nonculprit lesion (NCL) management in ST-segment-elevation myocardial infarction patients with multivessel disease is debated. We sought to assess whether quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, may be reliable in this scenario., Methods and Results: The present proof-of-concept study is based on a 3-step process: (1) identification of the QFR reproducibility in NCLs assessment (cohort A, n=31); (2) prospective validation of QFR diagnostic accuracy in respect to fractional flow reserve (cohort B, n=45); and (3) investigation of long-term clinical outcomes of NCLs stratified according to QFR (cohort C, n=110). A blinded core laboratory computed QFR values for all NCLs. Cohort A showed a good correlation and agreement between QFR values at index (acute) and at staged (subacute, 3-4 days later) procedures ( r =0.98; 95% confidence interval, 0.96-0.99; mean difference, 0.004 [-0.027 to 0.34]). The inter-rater agreement was κ=0.9. In cohort B, fractional flow reserve and QFR identified 16 (33%) and 17 (35%) NCLs potentially flow limiting. Sensitivity, specificity, negative, and positive predictive values were 88%, 97%, 94%, and 94%. The area under the receiver operating characteristics curve was 0.96 (95% confidence interval, 0.89-0.99). Finally, in cohort C, we identified 110 ST-segment-elevation myocardial infarction patients where at least 1 NCL was left untreated. Patients with NCLs showing a QFR value ≤0.80 were at higher risk of adverse events (hazard ratio, 2.3; 95% confidence interval, 1.2-4.5; P =0.01)., Conclusions: In a limited and selected study population, our study showed that QFR computation may be a safe and reliable tool to guide coronary revascularization of NCLs in ST-segment-elevation myocardial infarction patients., (© 2018 American Heart Association, Inc.)

Background: Patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES) on unprotected left main (ULM) represent a complex subset. The role of routine coronary angiography at follow up in this subset remains debated., Methods: At the documented center, all patients undergoing successful PCI on ULM lesions performing angiographic follow-up is suggested, but adherence to such a recommendation is inhomogeneous. Consecutive patients undergoing DES PCI on ULM were enrolled and experienced no adverse events during the first 6 months. Patients were then allocated to two groups: those undergoing routine control angiography (CA) and those undergoing clinical follow-up (CF). Primary endpoint was major adverse cardiac events (MACE) defined as cardiac death, myocardial infarction and urgent repeat target vessel revascularization., Results: A total of 190 patients underwent successful DES implantation on ULM and the study population was without early events. CA was performed at 6 months after the index procedure in 91 (48%) patients. After 35 ± 21 months, MACE rates were significantly more common in the CF group as compared with the CA group (16.2% vs. 4.3%, p = 0.009). At multivariable analysis, CA was associated with reduced MACE risk (HR 0.13, 95% CI 0.1-0.7, p = 0.028). Of note, this was mainly driven by higher cardiac death rate in those undergoing CF than in those undergoing CA (p = 0.01)., Conclusions: CA after complex PCI, such as ULM PCI, is associated with reduced MACE. Such an observation calls for appropriately designed randomized trials.

Background: The cause for discrepancy in the clinical presentation and outcome of coronary artery disease (CAD) between men and women is not established. Different prevalences of risk factors or specific sex-related atherosclerotic aspects have been advocated as possible explanations. We investigated coronary plaque morphology looking at possible differences in plaque vulnerability between men and women with stable CAD., Patients and Methods: We retrospectively collected and analyzed clinical data and coronary plaque morphology by frequency-domain optical coherence tomography in men and women with stable CAD., Results: A total of 181 (139 were in men and 42 in women) plaques from 138 patients were analyzed. The mean age was similar between men and women. Besides an overall absence of significant differences in the vast majority of risk factors and comorbidities, men had a higher prevalence of active smoking (19 vs. 2%, P=0.006), previous myocardial infarction (17 vs. 2%, P=0.01), and previous percutaneous coronary interventions (42 vs. 17%, P=0.003). Frequency-domain optical coherence tomography in women showed significantly more plaque-vulnerability features as testified by higher percent of lipid-rich plaques (55 vs. 36%, P=0.03), macrophages (21 vs. 5%, P=0.003), and microvessels (24 vs. 8%, P=0.01). Multivariate analysis showed that female sex was associated independently with lipid-rich plaques (P=0.034) and macrophages (P=0.001). In the analysis restricted to the more severe lesions that were revascularized, women continued to be characterized by more adverse morphological features, such as macrophages (30 vs. 7%, P=0.004) and lipid-rich plaques (63 vs. 39%, P=0.045)., Conclusion: Women with stable CAD may be characterized by plaques that have increased prevalence of vulnerability compared with men. These findings support the hypothesis of sex-specific differences in the development of atherosclerosis.

Aims: Microvascular obstruction (MVO) is associated with a worse prognosis in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI). However, data about incidence, clinical outcome and correlates of MVO in latecomers after STEMI are still lacking., Methods: We prospectively enrolled consecutive patients that were latecomers after STEMI (symptoms onset >12h) undergoing PCI. We performed an angiographic analysis to assess the occurrence of MVO [defined as TIMI flow grade ≤2 or 3 with a myocardial blush grade <2]. Moreover, we performed a clinical and echocardiographic follow-up to assess the occurrence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction and rehospitalization for heart failure, and to evaluate left ventricle remodelling., Results: Seventy-eight patients were enrolled [mean age 67.58±11.72years, 57 (73%) male; mean time of symptom onset 23.14±16.06h] with a mean follow-up time of 29.7±14.1months. MVO occurred in 39 (50%) patients. Patients with MVO had a higher rate of MACE [18 (46%) vs. 3 (8%), p<0.001] and LV remodelling [25 (64%) vs. 6 (15%), p<0.001] compared with patients without MVO. By multivariable Cox regression MVO and left anterior descending artery were independent predictors of MACE., Conclusions: Latecomers after STEMI have a high risk to develop MVO that is related to an adverse prognosis. Appropriate management and follow-up strategies should be implemented in such high-risk patients group., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Clinical consequences of optical coherence tomographic (OCT) high-definition visualization of plaque/stent structures in acute patients remain undefined. In this retrospective substudy, we assessed the prognostic impact of postprocedural culprit lesion OCT findings in patients with acute coronary syndrome undergoing percutaneous coronary intervention., Methods and Results: In the CLI-OPCI (Centro per la Lotta Contro L'Infarto-Optimization of Percutaneous Coronary Intervention) database collecting cases from 5 independent OCT-experienced centers, we retrospectively analyzed postprocedural OCT findings in acute coronary syndrome patients and explored its possible impact (specifically that of residual intrastent plaque/thrombus protrusion) on outcome. From 2009 to 2013, 507 patients (588 lesions) were evaluated. Patients experiencing device-oriented cardiovascular events showed more frequently the features of suboptimal stent implantation defined as the presence of significant residual intrastent plaque/thrombus protrusion (hazard ratio [HR], 2.35; P<0.01), in-stent minimum lumen area (MLA) <4.5 mm 2 (HR, 2.72; P<0.01), dissection >200 µm at distal stent edge (HR, 3.84; P<0.01), and reference lumen area <4.5 mm 2 at either distal (HR, 6.07; P<0.001) or proximal (HR, 8.50; P<0.001) stent edges. Postprocedural OCT assessment of treated culprit lesion revealed at least one of these parameters in 55.2% of cases, with an associated increased risk of device-oriented cardiovascular events during follow-up (17.9% versus 4.8%; P<0.001). Both the presence of at least one of these parameters (HR, 3.69; P=0.002) and the residual intrastent plaque/thrombus protrusion (HR, 2.83; P=0.008) were confirmed as independent predictors of device-oriented cardiovascular events., Conclusions: In this retrospective study of acute coronary syndrome patients undergoing percutaneous coronary intervention, a composite of OCT-defined suboptimal stent implantation characteristics at the culprit lesion and residual intrastent plaque/thrombus protrusion was associated with adverse outcome., (© 2016 American Heart Association, Inc.)

Aim: To assess the "real world" clinical outcome of patients with bifurcated lesions undergoing percutaneous coronary intervention with implantation of second and third generations of zotarolimus-eluting stent., Methods and Results: Nine Italian centres participated in a prospective multicentre clinical project evaluating the outcome of patients receiving zotarolimus-eluting Resolute stent and Resolute Integrity stents. Patients with bifurcated lesions entered this evaluation. Clinical characteristics and angiographic and procedural details were prospectively recorded. Clinical outcome was prospectively assessed to evaluate the occurrence of major adverse cardiac events (MACE). A total of 577 patients were enrolled. The target lesion was distal left main in 11.1% and left anterior descending artery in 52.8%, and 30.3% of lesions were Medina 1,1,1. At a mean follow-up time of 27.0 ± 13.5 months, the survival free from MACE was 91.8%. Survival free from MACE was similar in patients grouped according to different bifurcated lesion complexity. On the contrary, patients receiving a single stent had better survival free from MACE as compared with those with double stent (P = 0.005). At multivariable analysis, double stenting (but not bifurcated lesion complexity) was found to be a significant predictor of MACE (hazard ratio, 2.52; 95% confidence interval, 1.28-4.94; P = 0.007). Of note, patients receiving the second stent as a bail-out had worse survival free from MACE compared with those who received it as a planned technique (P = 0.045)., Conclusion: The treatment of patients with bifurcated lesions with second and third generation zotarolimus-eluting stents is associated with good long-term clinical outcomes. Clinical outcome seems to be independent of lesion complexity, but may be influenced by the stenting technique (single or double stenting as well as elective or bail-out double stenting). © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objectives: The goal of this study was to assess the clinical impact of optical coherence tomography (OCT) findings during percutaneous coronary intervention (PCI)., Background: OCT provides unprecedented high-definition visualization of plaque/stent structures during PCI; however, the impact of OCT findings on outcome remains undefined., Methods: In the context of the multicenter CLI-OPCI (Centro per la Lotta contro l'Infarto-Optimisation of Percutaneous Coronary Intervention) registry, we retrospectively analyzed patients undergoing end-procedural OCT assessment and compared the findings with clinical outcomes., Results: A total of 1,002 lesions (832 patients) were assessed. Appropriate OCT assessment was obtained in 98.2% of cases and revealed suboptimal stent implantation in 31.0% of lesions, with increased incidence in patients experiencing major adverse cardiac events (MACE) during follow-up (59.2% vs. 26.9%; p < 0.001). In particular, in-stent minimum lumen area <4.5 mm(2) (hazards ratio [HR]: 1.64; p = 0.040), dissection >200 μm at the distal stent edge (HR: 2.54; p = 0.004), and reference lumen area <4.5 mm(2) at either distal (HR: 4.65; p < 0.001) or proximal (HR: 5.73; p < 0.001) stent edges were independent predictors of MACE. Conversely, in-stent minimum lumen area/mean reference lumen area <70% (HR: 1.21; p = 0.45), stent malapposition >200 μm (HR: 1.15; p = 0.52), intrastent plaque/thrombus protrusion >500 μm (HR: 1.00; p = 0.99), and dissection >200 μm at the proximal stent edge (HR: 0.83; p = 0.65) were not associated with worse outcomes. Using multivariable Cox hazard analysis, the presence of at least 1 significant criterion for suboptimal OCT stent deployment was confirmed as an independent predictor of MACE (HR: 3.53; 95% confidence interval: 2.2 to 5.8; p < 0.001)., Conclusions: Suboptimal stent deployment defined according to specific quantitative OCT criteria was associated with an increased risk of MACE during follow-up., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the immediate and long-term outcomes of transradial (TR) percutaneous coronary intervention (PCI) to unprotected left main stem (ULMS) bifurcation and to assess the main aspects affecting access-site choice in this specific PCI setting., Background: TR-PCI to the ULMS is feasible, but data specifically comparing TR and transfemoral (TF) approaches in ULMS-bifurcation PCI are limited., Methods: We set up a two-center (Rome, Italy and Oxford, United Kingdom) retrospective registry aimed at comparing the immediate and 1-year outcomes of consecutive patients who underwent ULMS-bifurcation PCI with drug-eluting stent implantation from 2005 to 2013 using the TF or TR approach. Clinical endpoints were: total mortality; major adverse cardiac and cerebrovascular event (MACCE) rate; and net adverse clinical event (NACE) rate., Results: A total of 467 patients undergoing ULMS-bifurcation PCI were enrolled (221 TF and 244 TR). TR approach was increasingly adopted over time for both simple and complex procedures. No significant differences were observed between the TR and TF groups in terms of 1-year mortality (10.7% vs 9.8%; P=.79) and MACCE (18.2% vs 15.2%; P=.44). TR patients, as compared with TF, had significantly fewer access-site complications (2.0% vs 6.3% in TF; P=.02), resulting in a significant reduction of NACE rate (6.9% vs 15.7;%; P=.01)., Conclusion: In patients undergoing ULMS-bifurcation PCI, the selection of TR instead of TF approach is associated with similar early and long-term ischemic complications and with a significant reduction of access-site complications, resulting in lower NACE rate.

Plaque rupture (PR) and superimposed thrombosis have been shown as the most frequent underlying substrate in acute coronary syndromes (ACS). Coronary angiography is a luminogram not able to define in vivo features of the culprit plaques. The aim of the study was to use optical coherence tomography (OCT) to investigate the pathology underlying complex (CL) and non-complex angiographic lesions (NCL). We retrospectively enrolled 107 ACS patients admitted to our institution; 83 with non-ST elevation ACS (NSTE-ACS) and 24 with ST-elevation myocardial infarction. Coronary angiography was performed and culprit lesions were classified according to Ambrose criteria into NCL (n = 47) and CL (n = 60). OCT imaging was then performed to better identify plaque morphology; either PR or intact fibrous cap, the presence of superimposed thrombosis, lipid rich plaque, and thin cap fibroatheroma (TCFA). OCT analysis showed that 58 lesions (54.2%) were classified as PR and 48 lesions (44.9%) were associated with thrombi. Lipid rich plaques were identified in 62 lesions (57.9%). PR, intracoronary thrombi, lipid rich plaques and TCFA were more frequent in CL compared with NCL (71.7 vs 31.9%, 63.3 vs 21.3%, 71.7 vs 40.4% and 46.7 vs 21.3% respectively), but PR with superimposed thrombus may be also detected in NCL. OCT demonstrates PR and thrombosis in the majority of ACS patients presenting with CL. However, one-third of NCL show PR by OCT, suggesting that additional intracoronary imaging by OCT may better identify the underlying mechanism of coronary instability than coronary angiography alone.

Background: Endothelialisation is a crucial event after percutaneous coronary intervention (PCI). Endothelial progenitor cells (EPCs) are bone marrow derived elements with reparative properties. We aimed to assess the relationship between circulating EPC levels and stent neointimal hyperplasia (NIH) using frequency domain optical coherence tomography (FD-OCT)., Methods: Patients undergoing elective PCI to native vessels and randomised to bare metal stent (BMS) alone versus BMS plus drug coated balloon (DCB) were included. At six months, angiographic follow-up and FD-OCT were performed to measure percentage neointimal hyperplasia volume obstruction (%NIHV), and percentage of uncovered stent struts (%US). Venous blood samples were obtained before the procedure and at six months to detect CD34+CD45dimKDR+ EPC levels., Results: Twenty patients were enrolled. A significant relationship was observed between baseline EPC levels and %NIHV (R: 0.63, p: 0.03) and %US (R: -0.56, p: 0.01) at follow-up. Both EPC levels and DCB use were independently related to %NIHV (β: 0.55; p < 0.001 and β: -0.51; p: 0.001, respectively), while only EPC levels were independently associated to %US (β: -0.52; p: 0.01). Higher %NIHV (p: 0.004) and lower %US (p: 0.005) were observed in patients with stable or increasing EPC level., Conclusion: Our study shows a relationship between EPC levels and stent strut coverage, supporting a dual role for these cells in favouring stent endothelialisation but also NIH growth., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to assess the feasibility of unprotected non-ostial left main (LM) imaging by frequency domain optical coherence tomography (FD-OCT)., Methods and Results: We conducted a retrospective analysis of OCT studies performed to image lesions located in the non-ostial LM. OCT studies were analysed off-line to detect the number of artefact frames in the different LM/bifurcation segments. OCT cross-sectional images were used to assess area measures. OCT longitudinal reconstructions were used to obtain the LM length. Standard quantitative coronary angiography (QCA) was used as the reference methodology. A total of 54 patients with non-ostial LM disease entered the study. The mean number of LM artefact frames was 8±10, corresponding to 19% of the total number of LM frames analysed. The percentages of artefact frames differed significantly according to the segment analysed: 43.3% proximal LM, 11.4% mid LM and 2.1% distal LM, 2.0% ostial left anterior descending artery and 0% ostial left circumflex artery (p<0.0001). All LM OCT measurements were significantly correlated with QCA measurements., Conclusions: The results of the present study show that FD-OCT assessment of non-ostial LM disease is feasible and may provide high-quality imaging. OCT assessment of distal LM is more efficient than that of the proximal LM segment.

We describe our solution to the unusual situation of an inflated, large coronary stent (3.5 mm diameter) which became dislodged from the ostium of the right coronary artery after deployment during a transradial procedure. We discussed tips for retrieval from the radial artery while preserving the access for completion of the procedure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Our study aimed to elucidate mechanisms underlying discordance between fractional flow reserve (FFR) and hyperemic stenosis resistance (hSR) in some patient subsets. To do this, we enrolled 30 consecutive patients with stable angina or non-ST elevation myocardial infarction (non-STEMI) and with a nonculprit intermediate coronary lesion (40% to 70%) by coronary angiography. We measured aortic pressure, flow velocity, and pressure distal to lesion simultaneously at basal level and during adenosine-induced (fixed intracoronary dose of 120 μg) hyperemia using a dual-sensor-equipped guidewire. Microvascular resistance (MR; pressure distal to lesion/flow velocity, mm Hg/cm/s) and variation (Δ) in MR levels were calculated both at baseline and after hyperemia, whereas FFR (cutoff <0.80) and hSR [(aortic pressure - pressure distal to lesion)/flow velocity, cutoff >0.80 mm Hg/cm/s] were assessed after intracoronary adenosine. Twenty-three patients (76.7%) showed concordance and 7 patients (23.3%) showed discordance between FFR and hSR (all cases with FFR >0.80 and hSR >0.80). Discordant patients presented more frequently with non-STEMI (85.7% vs 39.1%, p = 0.04), significantly higher C-reactive protein serum levels (median [interquartile range] 5.9 [5.1 to 6.8] vs 4.9 [3.7 to 6.2] mg/L, p = 0.007), and lower ΔMR (p = 0.03) values compared with concordant patients. In conclusion, patients with non-STEMI and those with increased C-reactive protein levels show a lower reduction in MR after intracoronary adenosine-induced hyperemia, leading to FFR underestimation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Bifurcations represent challenging lesions which may benefit from improved understanding of stent-related vessel complications. Since optical coherence tomography (OCT) allows us to detect post-stenting vessel injuries, we sought to assess the geographic pattern of stent-related complications occurring during provisional stenting of bifurcated lesions., Methods and Results: Fifty-one patients with bifurcated lesions treated by provisional stenting and undergoing intra-procedural OCT assessment were enrolled. OCT images were acquired with the aim of guiding the percutaneous coronary intervention but were re-analysed off-line for the present study. The stented bifurcation was divided into four segments [three in the main vessel (MV) and one in the side branch (SB)]. The following acute post-stenting vessel injuries/complications at the different bifurcation segments were evaluated: (i) stent under-expansion, (ii) stent malapposition, (iii) stent edge dissection, (iv) side-branch ostium dissection, (v) tissue prolapse, (vi) intracoronary thrombus, and (vii) in-stent dissection. A total of 55 bifurcation lesions undergoing provisional stenting were analysed. At least one OCT complication was detectable in all cases. Across different bifurcation sites, significant differences in the occurrence of stent complications were observed. In particular, stent malapposition was more common at the proximal MV segment (P < 0.001), while tissue prolapse was more common at the distal MV segment (P < 0.001)., Conclusion: In bifurcated interventions, OCT often detects vessel injuries/stent complications, which tend to have a specific geographical distribution. In particular, stent malapposition is more common at the proximal MV and tissue prolapse at the distal MV segment.

Background: The management of patients with angiographically intermediate coronary lesions is a major clinical issue. Fractional flow reserve provides validated functional insights while optical coherence tomography provides high resolution anatomic imaging. Both techniques may be applied to guide management in case of angiographically intermediate coronary lesions. Moreover, these techniques may be used to optimize the result of percutaneous coronary intervention. We aim to compare the clinical and economic impact of fractional flow reserve versus optical coherence tomography guidance in patients with angiographically intermediate coronary lesions., Methods/design: Patients with at least one angiographically intermediate coronary lesion will be randomized (ratio 1:1) to fractional flow reserve or optical coherence tomography guidance. In the fractional flow reserve arm, percutaneous coronary intervention will be performed if fractional flow reserve value is ≤0.80, and will be conducted with the aim of achieving a post-percutaneous coronary intervention fractional flow reserve target value of ≥0.90. In the optical coherence tomography arm, percutaneous coronary intervention will be performed if percentage of area stenosis (AS%) is ≥75% or 50 to 75% with minimal lumen area <2.5 mm2, or if a major plaque ulceration is detected. In case of percutaneous coronary intervention, optical coherence tomography will guide the procedure in order to minimize under-expansion, malapposition, and edge dissections.Cost load and clinical outcome will be prospectively assessed at one and thirteen months. The assessed clinical outcome measures will be: major cardiovascular events and occurrence of significant angina defined as a Seattle Angina Questionnaire score <90 in the angina frequency scale., Discussion: The FORZA trial will provide useful guidance for the management of patients with coronary artery disease by prospectively assessing the use of two techniques representing the gold standard for functional and anatomical definition of coronary plaques., Trial Registration: Clinicaltrials.gov NCT01824030.

Aims: Angiographic guidance for percutaneous coronary intervention (PCI) has substantial limitations. The superior spatial resolution of optical coherence tomography (OCT) could translate into meaningful clinical benefits. We aimed to compare angiographic guidance alone versus angiographic plus OCT guidance for PCI., Methods and Results: Patients undergoing PCI with angiographic plus OCT guidance (OCT group) were compared with matched patients undergoing PCI with angiographic only guidance (Angio group) within 30 days. The primary endpoint was the one-year rate of cardiac death or myocardial infarction (MI). A total of 670 patients were included, 335 in the OCT group and 335 in the Angio group. OCT disclosed adverse features requiring further interventions in 34.7%. Unadjusted analyses showed that the OCT group had a significantly lower one-year risk of cardiac death (1.2% vs. 4.5%, p=0.010), cardiac death or MI (6.6% vs. 13.0%, p=0.006), and the composite of cardiac death, MI, or repeat revascularisation (9.6% vs. 14.8%, p=0.044). Angiographic plus OCT guidance was associated with a significantly lower risk of cardiac death or MI even at extensive multivariable analysis adjusting for baseline and procedural differences between the groups (OR=0.49 [0.25-0.96], p=0.037) and at propensity-score adjusted analyses., Conclusions: This observational study, the first ever formally to appraise OCT guidance for PCI decision-making, suggests that the use of OCT can improve clinical outcomes of patients undergoing PCI.

Angiographic evaluation of intermediate left main coronary artery stenosis (LMS) is often limited. Three-dimensional (3D) quantitative coronary angiography has recently developed to overcome 2-dimensional (2D) quantitative coronary angiographic (QCA) limitations. In patients with angiographically intermediate LMS, we investigated whether 3D quantitative coronary angiography was superior to 2D quantitative coronary angiography in predicting the presence of a significant LMS, defined as a minimum luminal area <6 mm(2) at intravascular ultrasound (IVUS). 2D and 3D quantitative coronary angiography were compared in their measurements of minimum luminal area, percent area stenosis, minimum luminal diameter, and percent diameter stenosis and in their prediction of an IVUS minimum luminal area <6 mm(2). In total 58 target lesions were interrogated, 25 (43%) of which had an IVUS minimum luminal area <6 mm(2). Correlation between 3D-QCA minimum luminal area and IVUS minimum luminal area was stronger than the correlation between 2D-QCA minimum luminal area (or minimum luminal diameter) and IVUS minimum luminal area (R = 0.67, p = 0.0001, and R = 0.40, p = 0.001, respectively, p = 0.04 for comparison). To predict IVUS minimum luminal area <6 mm(2), the most accurate 2D-QCA measurement was minimum luminal diameter (area under curve 0.81, cutoff 2.2 mm, p = 0.0001), and the most accurate 3D-QCA measurement was minimum luminal area (area under curve 0.86, cutoff 5.6 mm(2), p = 0.0001). 2D-QCA percent diameter stenosis did not significantly predict IVUS minimum luminal area <6 mm(2) (area under curve 0.56, cutoff 38%, p = 0.45). In conclusion, the accuracy of quantitative coronary angiography in predicting LM IVUS minimum luminal area <6 mm(2) is limited. When IVUS is not available or contraindicated, 3D quantitative coronary angiography may assist in the evaluation of intermediate LMS. Among 2D-QCA parameters, minimum luminal diameter is more accurate than percent diameter stenosis in predicting significant LMS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Neointimal hyperplasia plays a pivotal role in the pathogenesis of in-stent restenosis in patients undergoing percutaneous coronary interventions. Drug-eluting balloons are a promising tool to prevent restenosis after coronary angioplasty. Moreover, an increased knowledge of the pathophysiology of restenosis my help improve therapeutic strategies., Methods/design: We present the design of an open-label, randomized three-arm clinical trial aimed to assess whether a strategy of bare-metal stent implantation with additional use of drug-eluting balloons, either before (pre-dilation) or after stenting (post-dilation), reduces the primary endpoint of in-stent neointimal hyperplasia area as compared with a strategy of bare-metal stent implantation alone. This primary endpoint will be assessed by optical coherence tomography at follow-up. Secondary endpoints will be the percentage of uncovered struts, and the percentage of struts with incomplete apposition. An ancillary study investigating the relation between systemic levels of endothelial progenitors cells and neointimal hyperplasia, and the interaction between endothelial progenitors cell levels and drug-eluting balloons has been planned. Thirty consecutive patients undergoing percutaneous coronary intervention will be randomized with a 1:1:1 design to bare-metal stent implantation alone (n = 10); bare-metal stent implantation after pre-dilation with a drug-eluting balloon (n = 10); or bare-metal stent implantation followed by post-dilation with a drug-eluting balloon (n = 10). Six-month follow-up coronary angiography with optical coherence tomography imaging of the stented segment will be performed in all patients. Blood samples for the assessment of endothelial progenitors cell levels will be collected on admission and at 6 months., Discussion: Experimental and early clinical data showed that inhibition of neointimal hyperplasia may be obtained by local administration of antiproliferative drugs loaded on the surface of angioplasty balloons. The INtimal hyPerplasia evAluated by oCT in de novo COROnary lesions treated by drug-eluting balloon and bare-metal stent (IN-PACT CORO) trial was conceived to test the superiority of a strategy of bare-metal stent implantation with additional drug-eluting balloon use (either before or after stenting) versus a strategy of bare-metal stent implantation alone for the reduction of neointimal hyperplasia. We also planned an ancillary study to assess the role of endothelial progenitors cells in the pathophysiology of neointimal hyperplasia., Trial Registration: Clinicaltrials.gov NCT01057563.

Background: In the treatment of coronary bifurcation lesions (CBL), with drug eluting stents (DES), we sought to compare angiographic and clinical outcomes of a simple strategy of stenting main vessel only with balloon dilatation of the side branch with a complex strategy of stenting both branches., Methods: We performed a meta-analysis of six studies, randomized (three) or prospective observational (three), including 963 patients, that directly compared the simple strategy to the complex strategy, in the treatment of CBL with DES., Results: Final minimal lumen diameter (MLD) of the side branch was significantly smaller in the simple strategy group [WMD -0.50 mm, 95% CI (-0.76, -0.24), p<0.00001]. The risk of main vessel restenosis [RR 0.66, 95% CI (0.38-1.17), p=0.16], side branch restenosis [RR 0.62, 95% CI (0.24-1.56), p=0.31], follow up death [RR 0.60, 95% CI (0.19-1.86), p=0.38], follow up myocardial infarction [RR 0.71, 95% CI (0.46-1.10), p=0.13], or target vessel revascularization [RR 0.90, 95% CI (0.56-1.46), p=0.67] was similar between the two strategies. The simple strategy showed a trend to a lower risk of early myocardial infarction [RR 0.65, 95% CI (0.41-1.05), p=0.08]., Conclusion: In the treatment of unselected CBL with DES, the complex strategy does not penalize angiographic and clinical outcomes compared to the simple strategy. Further randomized studies are needed to assess the benefit of simple or complex strategy in the treatment of specific subsets of bifurcated lesions., (Copyright 2008 Elsevier Ireland Ltd. All rights reserved.)

Objective: The role of oxidised low-density lipoprotein (ox-LDL) in plaque destabilisation is controversial; therefore we aimed at comparing plaque and plasma ox-LDL content in stable and unstable ischaemic syndromes. We also assessed the correlation between plaque or plasma ox-LDL and angiographic complex stenosis morphology., Methods: Ten consecutive patients with chronic stable angina (SA) and 10 consecutive patients with unstable angina (UA) were studied. Plaque sections obtained by directional coronary atherectomy were immunostained with the monoclonal antibody mAb-4E6, which recognises several oxidation epitopes on LDL (mAb-4E6 ox-LDL), and with the monoclonal antibody mAb-1H11 (mAb-1H11 ox-LDL), which recognises malondialdehyde-modified LDL. An mAb-4E6-based competition ELISA was used for quantification of ox-LDL in plasma. C-reactive protein serum levels were measured by a high-sensitivity nephelometric assay. An angiographic analysis was performed to assess severity and extent of coronary atherosclerotic disease and stenosis morphology., Results: Percent plaque area occupied by mAb-4E6 ox-LDL or mAb-1H11 ox-LDL was similar in patients with SA or UA (22.4 +/- 13.1 vs. 21.1 +/- 19.7%, P = 0.8 and 19.3 +/- 10.4 vs. 16.8 +/- 16.9%, P = 0.6, respectively), whereas ox-LDL plasma levels were significantly higher in patients with UA than in patients with SA (2.4 +/- 1.1 vs. 0.9 +/- 0.6 mg/dl; P = 0.03). Furthermore, a significant correlation was found between plasma levels of ox-LDL and the number of angiographically complex lesions (P = 0.03) or C-reactive protein serum levels (P = 0.04)., Conclusions: Neither plaque mAb-4E6 ox-LDL nor plaque mAb-1H11 ox-LDL seem to be a major trigger of coronary plaque instability. However, circulating ox-LDL might be involved in plaque vulnerability and coronary artery disease activity.

Background: The main limitation of myocardial single photon emission computed tomography (SPECT) in detecting hibernating myocardium is the poor delivery of radiotracers in hypoperfused areas supplied by severely stenotic coronary arteries. Increasing local availability of radiotracers by intracoronary injection might represent an attractive solution. The hypothesis that the intracoronary administration of sestamibi could improve myocardial SPECT accuracy in detecting hibernating myocardium was addressed in this pilot study., Methods and Results: Seven patients with prior myocardial infarction and severe stenosis of the infarct-related artery underwent myocardial SPECT after intracoronary injection of technetium 99m sestamibi immediately before percutaneous transluminal coronary angioplasty (PTCA). Wall motion and perfusion were evaluated, before and 1 month after PTCA, by 2-dimensional echocardiography and rest-redistribution thallium 201 SPECT. A "low-flow area" was identified on the pre-PTCA Tl-201 SPECT image as the area with less than 50% of maximum radiotracer uptake. Changes in wall motion and perfusion in the low-flow area were compared with results of intracoronary sestamibi imaging. On a pixel-by-pixel analysis, intracoronary sestamibi predicted perfusion recovery within the low-flow area with a 91% sensitivity, a 78% specificity, and an 82% overall accuracy. Only in the 5 patients with an extent of sestamibi uptake greater than one third of the low-flow area was an improved regional and global left ventricular wall motion observed after PTCA (wall motion score index decreased from 1.95 +/- 0.28 to 1.60 +/- 0.34, P =.007; left ventricular ejection fraction increased from 42% +/- 7% to 49% +/- 7%, P =.001; asynergic segments in the low-flow area decreased from 3.6 +/- 0.9 to 1.8 +/- 1.5, P =.021)., Conclusions: In patients with prior myocardial infarction and severe stenosis of the infarct-related artery, sestamibi uptake after intracoronary administration identified viable myocardium that was undetected after rest-redistribution thallium SPECT but capable of clinically significant contractile improvement after revascularization.