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There is limited evidence regarding the association between right ventricular-to-pulmonary artery (RV-PA) coupling and outcomes after transcatheter aortic valve replacement (TAVR). This study aimed to explore the evolution of RV-PA coupling in patients with severe aortic stenosis undergoing TAVR and its prognostic impact. A total of 900 patients who underwent TAVR in 2 tertiary centers and with echocardiographic analysis performed within 3 months before and after the procedure were included. RV-PA coupling was measured as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). RV-PA uncoupling was defined by TAPSE/PASP <0.55, whereas a TAPSE/PASP <0.32 identified a severe uncoupling. The primary endpoint was all-cause mortality. A total of 520 patients (58%) showed RV-PA uncoupling before TAVR, whereas post-TAVR RV-PA uncoupling was observed in 407 patients (45%). During a median follow-up of 40 months, 250 deaths (28%) occurred. Post-TAVR RV-PA uncoupling was independently associated with an increased risk of mortality (adjusted HR: 1.474; 95% CI: 1.115-1.948; P = 0.006), whereas pre-TAVR uncoupling did not. Among patients with post-TAVR RV-PA uncoupling, the presence of severe uncoupling identified a subgroup with the worst survival (P = 0.008). Patients with RV-PA coupling recovery after TAVR showed similar outcomes as compared with patients with normal coupling. Conversely, the presence of either persistent or new-onset RV-PA uncoupling following TAVR was associated with an increased mortality risk. Post-TAVR RV-PA uncoupling is an independent predictor of long-term mortality, irrespective of coupling before intervention. Assessment of TAPSE/PASP response after TAVR may be helpful to improve risk stratification. [Display omitted] [ABSTRACT FROM AUTHOR]

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Abstract: Background: Previous studies demonstrated that patients with PIA have a smaller infarct and better in-hospital outcome after acute myocardial infarction, than those without angina. This protective effects has been attributed to ischemic preconditioning (PC), to earlier reperfusion after fibrinolysis or its better collateral circulation development. In this study we aimed at assessing platelet reactivity in patients with history of pre-infarction angina (PIA) in the acute phase of ST segment elevation myocardial infarction (STEMI) and 1month later. Methods: 85 consecutive patients (63±10.5years, 60 male) with a first STEMI treated by primary percutaneous coronary intervention (PCI) were studied at admission and 1month later. Platelet reactivity was evaluated by flow cyometry with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate. Results: MPAs and expression of platelet receptors CD41 and PAC-1 were significantly lower in patients with than patients without PIA, both with and without ADP stimulation. After 1month, all cytometry variables both with and without ADP stimulation were similar in the two groups. Conclusions: This study shows, for the first time, that patients with a first STEMI who experience PIA show a lower platelet reactivity as compared with those without history of PIA. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the 30-day and long-term clinical outcomes of patients with carotid obstructive disease (COD) and concomitant coronary artery disease (CAD) undergoing a combined percutaneous revascularization, in 4 high-volume centers skilled for the treatment of multilevel vascular disease. Background: The optimal management of patients with COD and concomitant CAD remains controversial. A variety of therapeutic strategies, including coronary artery bypass grafting, alone or in combination with carotid artery revascularization, have been reported. Methods: Between January 2006 and April 2010, 239 consecutive patients with COD (symptomatic carotid stenosis in 20.5%) and concomitant CAD were treated with staged or simultaneous carotid artery stenting and percutaneous coronary intervention, and enrolled in this prospective registry. The primary endpoint was the incidence of major cardiac and cerebrovascular events, including any death, myocardial infarction, or stroke occurring between the first revascularization procedure and 30 days after treatment of the second vascular territory affected. Results: The incidence of the primary endpoint at 30 days was 4.2% (95% confidence interval [CI]: 2.02 to 7.56). The rate of death, myocardial infarction, and stroke at long-term follow-up (median 520 days) was 4.2%, 2.1%, and 3.8%, respectively. At long-term follow-up, patients with previous cardiovascular disease had significantly higher rates of major cardiac and cerebrovascular events than did patients with a first clinical episode (17% vs. 6%, hazard ratio: 3.34; 95% CI: 1.46 to 7.63; p = 0.004). Conclusions: In patients with COD and concomitant CAD, a combined percutaneous treatment compares favorably with previous surgical or hybrid experiences. Such strategy may be particularly suited to complex patients at high surgical risk. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: We previously showed that platelet reactivity at rest is increased in patients with cardiac syndrome X (CSX), but that exercise reduces platelet reactivity in these patients. Adenosine was suggested to be involved in this phenomenon. In this study we investigated the effect of adenosine on adenosine diphosphate (ADP) and thrombin-induced platelet reactivity in CSX patients. Materials and methods: We studied 15 CSX patients and a control group of 15 healthy subjects. Formation of monocyte-platelet (MONO-PLT) aggregates in vitro was assessed by flow cytometry: 1) at baseline; 2) after ADP (10-7 M) stimulation alone; 3) after ADP stimulation in presence of adenosine (10-5 M); 4) after thrombin (10-11 M) stimulation alone; 5) after thrombin stimulation in presence of adenosine. Results: In non stimulated samples there were no relevant differences between the two groups in cytometry variables. Compared to controls, ADP induced a higher increase in MONO-PLT aggregates in CSX patients (P<0.01), which was significantly inhibited by adenosine (P<0.01). Thrombin also induced a greater increase in MONO-PLT aggregates in CSX patients (P<0.001), which was also significantly blunted by adenosine. Similar trends were observed for platelet CD41 (glycoprotein IIb-IIIa) receptor and for monocyte receptors CD142 ad CD162 in MONO-PLT aggregates. Conclusions: In CSX patients platelet reactivity is increased at rest, compared to healthy controls. Pre-incubation with adenosine reduces the agonist-induced platelet hyper-reactivity in these patients, suggesting that adenosine may be involved in the reduction of platelet reactivity observed in CSX patients after exercise in our previous study. [Copyright &y& Elsevier]

Abstract: Introduction: In previous studies we have consistently shown a significant increase of platelet reactivity after exercise in patients with obstructive coronary artery disease (CAD). We also observed a significant individual variability in the response to exercise of platelet reactivity in these patients. Whether exercise-induced changes in platelet reactivity correlate with changes in platelet membrane receptors in patients with CAD is unknown. Methods: We studied 26 patients with stable CAD and 10 matched healthy controls who underwent a symptom-limited treadmill exercise stress test. Venous blood samples were collected at rest and within 5 min of peak exercise. Platelet reactivity was measured by the PFA-100 method as time to occlude (closure time, CT) a ring coated with collagen/adenosine diphosphate (C/ADP). Platelet expression of glycoprotein (GP) IIb/IIIa, in both global (CD41) and active form (PAC-1), and P-selectin (CD62P) and formation of leukocyte–platelet aggregates were assessed by flow cytometry. Results: After exercise CT did not change in controls (85.4±12 to 84.0±9 s, p =0.37), whereas it decreased in CAD patients (98.8±24 to 91.4±25 s, p <0.001). After exercise, CD41 and PAC-1 platelet expression increased significantly in CAD patients (p =0.04 for both), but not in controls (p =0.39 and p =0.98, respectively). To evaluate the relationship between the response to exercise of platelet reactivity and of platelet receptor expression, CAD patients were divided into two groups: CAD group 1 (16 patients, decrease in CT >5 s after exercise) and CAD group 2 (10 patients no increase in platelet reactivity after exercise). CD41 and PAC-1 expression increased in CAD group 1 (p =0.008 and p =0.026, respectively) but not in CAD group 2 (p =0.39 and p =0.50, respectively). No significant differences were observed between the 2 groups for changes in CD62P and leukocyte–platelet aggregates. Conclusions: Our data show that, in patients with stable CAD, an increased platelet reactivity to C/ADP stimulation after exercise, as assessed by the PFA-100 method, is specifically associated with an increased expression of platelet GP IIb/IIIa receptor. [Copyright &y& Elsevier]

Vascular complications (VCs) still represent one of the principal concerns of trans-femoral trans-catheter aortic valve replacement (TF-TAVR). New-generation devices can minimize such complications but the arterial access management is left to the operator's choice. This study aims to describe the rate of VCs in a contemporary cohort of patients undergoing TAVR with new-generation devices and to determine whether an ultrasound-guided (USG) vs. a fluoroscopy-guided (FG) femoral access management has an impact on their prevention. This is a prospective, observational, multicenter study. Consecutive patients undergoing TAVR with new-generation devices were analyzed from January 2022 to October 2022 in five tertiary care centers. Femoral accesses were managed according to the operator's preferences. All the patients underwent a pre-discharge peripheral ultrasound control. VCs and bleedings were the main endpoints of interest. A total of 458 consecutive patients were enrolled (274 in the USG group and 184 in the FG group). VCs occurred in 6.5 % of the patients (5.2 % minor and 1.3 % major). There was no difference between the USG and the FG groups in terms of any VCs (7.3 % vs. 5.4 %; p = 0.4), or any VARC-3 bleedings (6.9 % vs 6 %, p = 0.9). At logistic regression analysis, the two guidance strategies did not result as predictors of VCs (odds Ratio 0.8, 95 % Confidence Interval 0.46–1.4; P = 0.4). In a contemporary cohort of patients undergoing TAVR with new-generation devices, the occurrence of VCs is low and mostly represented by minor VCs. USG and FG modalities did not affect the rate of VCs. Central Illustration – Ultrasound-guided vs. Fluoroscopy-guided puncture in contemporary TF-TAVR procedures. Abbreviations : FG: fluoroscopy-guided; TF-TAVR: trans-femoral trans-catheter aortic valve replacement; USG: ultrasound-guided. [Display omitted] • TAVR with new-generation devices are associated with a low incidence of VCs • Most of the occurred VCs are minor • The modality to obtain the main access (USG vs FG) seems not to affect the rate of VCs [ABSTRACT FROM AUTHOR]

Coronary artery obstruction (CAO) during transcatheter-aortic-valve replacement (TAVR) represents a main concern for TAVR safety in patients with low coronary take-off. To date, "snorkel" (also called chimney) technique, consisting of stent implantation from the coronary ostium to the aorta within the space between the valve frame and the aortic wall, is the most adopted strategy to prevent CAO. This technique is associated with the creation of complex valve/stent configuration that can hinder repeat coronary interventions. Due to this concern, we set up an original sequence for coronary protection aiming to ensure a more physiological TAVR frame/stent configuration. According to this technique, TAVR prosthesis is released with a "protection" system consisting of guiding catheter (GC), wire and stent inside the coronary artery with high CAO risk. In the case of CAO occurrence, the stent is released according to the snorkel technique. In the absence of complete CAO, a new GC is advanced inside the implanted TAVR prosthesis and the stent is deployed from the coronary artery up to the prosthesis. We herein report two cases of very high CAO risk where this technique was successfully used during last-generation self-expandable prostheses implantation (in a native aortic valve and in one prosthetic aortic valve). In conclusion, this "orthotopic snorkel-stenting in TAVR" (OST) technique represents a novel option for treating impeding CAO during TAVR. As compared with the "classic" snorkel technique, it allows avoiding stent implantation in some patients (who do not experience CAO) and may provide a more predictable and physiologic TAVR prosthesis/stent configuration in the case of stent implantation need. [ABSTRACT FROM AUTHOR]

Background: Optical-coherence-tomography (OCT) is an emerging invasive coronary imaging with still undefined clinical value. Recent data have underlined daily impact of such technique in several clinical settings such as acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) guidance. We aimed at assessing the trends and outcomes of OCT use in a high-volume percutaneous coronary interventions (PCI)-center.Methods: Over 6 years, 1025 coronary artery segments in 877 patients underwent OCT evaluation. Clinical and procedural characteristics were prospectively collected. Clinical setting for OCT was: "Diagnostic OCT" (OCT for lesion evaluation after coronary angiography without further PCI); "PCI-guidance OCT" (OCT as a guidance for complex PCI, both by intention or after diagnostic OCT). Primary study end-point was the occurrence of target-vessel-failure (TVF) during the follow-up.Results: Overall, OCT was successful in 99.1% of attempted lesions. Only one complication (coronary dissection requiring urgent PCI) occurred during OCT. After a follow-up of 695 ± 562 days, TVF occurred in 8.2% of cases. Despite similar baseline characteristics, TVF-free survival curves were different in the two populations (5.4% after diagnostic OCT and 9.9% after PCI-guidance OCT). Minimal-lumen-area (MLA) of target lesion was independently associated with TVF (HR 0.7, 95% CI 0.6-0.8). This was mainly driven by a significant impact of MLA in patients not revascularized (HR 0.6, 95% CI 0.4-0.9). TVF did not change according to the study period despite the selection of patients with increasing complexity.Conclusions: OCT has a good safety profile across a broad spectrum of patients encountered in daily practice. The easy-to-assess MLA parameter may help stratify prognosis of patients undergoing OCT. These data call for further evaluations of OCT clinical impact.Summary: OCT is a light-based imaging tool which had subvert the quite ordinary world of coronary imaging and the present study evaluates OCT use in a high-volume center. Our results suggest that application of OCT in "real world" patients presenting higher risk has a good safety profile. Several factors could predict a worse long-term outcome in patients undergoing OCT evaluation, mostly related to more complex clinical conditions. These findings could encourage even low-to intermediate volume centers to improve their OCT use in daily practice. [ABSTRACT FROM AUTHOR]

Background: Coronary vasomotor abnormalities are important causes of myocardial ischemia in patients with nonobstructive coronary artery disease (NOCAD). However, the role of air pollution in determining coronary vasomotor disorders has never been investigated.Objectives: We aimed to evaluate the association between long-term exposure to particulate matter 2.5 (PM2.5) and 10 (PM10), and coronary vasomotor disorders in NOCAD patients.Methods: Patients with myocardial ischemia and NOCAD undergoing coronary angiography and intracoronary provocation test with acetylcholine were prospectively studied. Both patients with chronic myocardial ischemia and nonobstructive coronary arteries and myocardial infarction with nonobstructive coronary arteries (MINOCA) were enrolled. Based on each case's home address, exposure to PM2.5 and PM10 was assessed.Results: We included 287 patients (median age, 62.0 years [IQR: 52.0-70.0 years], 149 [51.9%] males); there were 161 (56.1%) myocardial ischemia and nonobstructive coronary arteries and 126 (43.9%) MINOCA cases. One hundred seventy-six patients (61.3%) had positive provocation test. Exposure to PM2.5 and PM10 was higher in patients with a positive provocation test (P < 0.001). At multivariate logistic regression analysis, PM2.5 and PM10 were independent predictors of a positive provocation test (P = 0.001 and P = 0.029, respectively). Interestingly, among these patients, PM2.5 and PM10 were both independent predictors of MINOCA (P < 0.001 and P = 0.001, respectively) as clinical presentation, whereas PM2.5 was independently associated with the occurrence of epicardial spasm as opposed to microvascular spasm (P = 0.001).Conclusions: Higher exposure to PM2.5 and PM10 in patients with myocardial ischemia and NOCAD is associated with coronary vasomotor abnormalities. In particular, PM2.5 is an independent risk factor for the occurrence of epicardial spasm and MINOCA as clinical presentation. [ABSTRACT FROM AUTHOR]

Contrast fractional flow reserve (cFFR) is a relatively new tool for the assessment of intermediate coronary artery stenosis and represents a reliable surrogate of FFR with the advantage of potentially simplifying functional evaluation. We aimed to compare the incidence of major adverse cardiac events (MACE) in patients undergoing functional evaluation with both FFR and cFFR based on the results of the two indexes. We retrospectively analyzed outcomes in 488 patients who underwent functional evaluation with FFR and cFFR. Patients were divided into four groups using the cutoff values of 0.80 for FFR and 0.85 for cFFR: −/− (n = 298), +/+ (n = 134), −/+(n = 31) and +/− (n = 25). All patients were treated according to FFR value. MACE rate was assessed in each group, including death, myocardial infarction and urgent target vessel revascularization (TVR). Mean follow-up time was 22 ± 15 months. Incidence of MACE at follow-up was 8.3% in FFR−/cFFR−, 14.0% in FFR+/cFFR+, 16.0% in FFR−/cFFR+ and 8.0% in FFR+/cFFR− without a significant difference amongst the 4 groups (p = 0.2). Nevertheless, a significant difference in the rate of TVR comparing FFR−/cFFR− (n = 17) and FFR−/cFFR+ (n = 5) was found at 24 months (5.7% vs 16.0%; p = 0.027). cFFR is accurate in predicting FFR and consequently reliable in guiding coronary revascularization. In the rare case of discordance, while FFR+/cFFR- patients show a prognosis similar to FFR-/cFFR- patients, FFR-/cFFR+ patients show a prognosis similar to FFR+/cFFR+ patients. • cFFR is a new tool in the assessment of intermediate coronary stenosis. • cFFR is accurate in predicting FFR and reliable in guiding revascularization. • In case of discordance, no significant difference in outcome choosing cFFR. • In patients with FFR > 0.80 and cFFR ≤ 0.85 TVR is higher. • cFFR could be a more sensitive index. [ABSTRACT FROM AUTHOR]

• Semi-automatic segmentation of pre- and post-operative OCT images. • 3D modelling of an ulcerated coronary artery lesion from OCT and angiography. • Pre- and post-operative patient-specific CFD model of an ulcerated coronary artery. The rupture of a vulnerable plaque, known as ulceration, is the most common cause of myocardial infarction. It can be recognized by angiographic features, such as prolonged intraluminal filling and delayed clearance of the contrast liquid. The diagnosis of such an event is an open challenge due to the limited angiographic resolution and acquisition frequency. The treatment of ulcerated plaques is an open discussion, due to the high heterogeneity and the lack of evidences that support particular strategies. Therefore, the therapeutic decision should follow a detailed investigation with angiography and intravascular imaging, such as optical coherence tomography (OCT), to locate the lesion, besides its geometric features and the lumen occlusion severity. The aim of this study is the application of a framework for the in-silico analysis of the disrupted hemodynamics due to an ulcerated lesion. The study employed a validated OCT-based reconstruction methodology and computational fluid dynamics (CFD) simulations for the computation of local hemodynamic quantities, such as wall shear stress. The reported findings, such as disrupted pre-operative flow conditions, proved the applicability of the developed framework for CFD analyses on complicated patient-specific anatomies that feature ulcerated plaques. The prediction of lesion expansion and the clinical decision making can benefit from a reliable computation of wall shear stress distributions that result from the peculiar anatomy of the lesion. The application of intravascular OCT imaging, high fidelity 3D reconstructions and CFD simulations might guide the treatment of such pathology. [ABSTRACT FROM AUTHOR]

Dual quantitative coronary angiography (QCA) has been recently tested for assessment of intracoronary thrombus volume in experimental models. The present study aimed to validate dual QCA in vivo for the assessment of thrombus burden by exploring the correlations between dual QCA-thrombus volume and optical coherence tomography (OCT)-derived indices of thrombotic burden. Fifty-one patients with ACS and angiographic evidence of thrombus undergoing OCT of the culprit lesion before stenting were included. Dual QCA-thrombus volume was calculated as difference between edge-detection and video-densitometry area functions along the target segment. Culprit lesion was categorized using the Ambrose's and AHA/ACC angiographic classifications. Thrombus volume (mean thrombus area × thrombus length), thrombus burden [(mean thrombus area/mean lumen area) x100] and Prati thrombus score (number of quadrants with thrombus) were measured by OCT, and the presence of plaque rupture (PR) or intact fibrous cap (IFC) was assessed. Dual QCA-thrombus volume correlated significantly with OCT-thrombus volume (R = 0.791), thrombus burden (R = 0.767) and Prati thrombus score (R = 0.600) (all p < 0.001). Dual-QCA thrombus volume was significantly higher in patients with PR compared with those with IFC (3.48 mm3 [1.45–11.26] vs. 1.69 mm3 [0.09–5.02], p = 0.013). Compared with IFC, PR showed higher prevalence of eccentric type II Ambrose lesion (41.7% vs. 7.4%, p = 0.004), complex B2/C lesion (87.5% vs. 55.6%, p = 0.012), and heavy calcification (29.2% vs. 3.7%, p = 0.013). Dual QCA analysis appears to be a promising tool for quantification of intracoronary thrombus in vivo. This novel methodology may be useful to guide intracoronary thrombus removal during percutaneous coronary intervention and to aid prognostic stratification in patients with ACS. Unlabelled Image • Dual quantitative coronary angiography (QCA) has been tested for the assessment of thrombus volume in experimental models. • In this in vivo study, dual QCA-thrombus volume was correlated with optical coherence tomography indices of thrombus burden. • A combination of angiographic features may enable the discrimination of patients with plaque rupture and intact fibrous cap. • Dual QCA may be useful to guide thrombus removal and aid prognostic stratification in patients with acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Abstract Background Fractional Flow Reserve (FFR) in Stable Ischemic Heart Disease (SIHD) is universally accepted, while in Acute Coronary Syndromes (ACS) is less established. Aims of this retrospective study were: to compare in patients undergoing FFR assessment the prognostic impact of ACS vs SIHD, to evaluate the clinical relevance of the modality of utilization and timing of FFR assessment and to assess the different outcomes associated with an FFR> or ≤0.80. Methods Major cardiac adverse events were assessed at a follow up of 16.4 ± 10.5 months in 543 patients with SIHD and 231 with ACS needing functional evaluation. FFR was used for lesions of ambiguous significance in the absence of a clear culprit vessel (first intention, FI) and for incidental lesions in the presence of a clear culprit vessel (second intention, SI). The decision to perform FFR and the identification of the stenosis needing functional assessment were left to the operator's discretion. Revascularization was performed when FFR was ≤0.80. Results SIHD and ACS patients were not significantly different for principal clinical characteristics. ACS patients had significantly more events than SIHD, due to an excess of death and myocardial infarction. This was confirmed when FFR was used as FI, in particular if FFR was >0.80. On the contrary, when FFR was used as SI, event rates were similar between ACS and SIHD patients, regardless of FFR value. Conclusions Our study shows that using FFR the risk of recurrent events in ACS is significantly higher than in SIHD. This different outcome is confined to those patients in whom FFR is utilized for lesions of ambiguous significance in the absence of a clear culprit vessel. Highlights • Role of Fractional Flow Reserve (FFR) in Acute Coronary Syndromes (ACS) is matter of debate. • Our study shows that using FFR the risk of recurrent events in ACS is significantly higher than in SIHD. • The different outcome is confined to patients in whom FFR is utilized in absence of a clear culprit vessel. [ABSTRACT FROM AUTHOR]

Abstract 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+CD28null T-cells, lower regulatory T-cells (Treg) and increased CD4+CD28null/Treg ratio. We sought to investigate the correlation between CD4+CD28null T-cells, Treg, CD4+CD28null/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+CD28null and Treg (defined as CD4+CD25highCD127lowFoxp3+ T-cells) by flow-cytometry. Results CD4+CD28null 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+CD28null/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+CD28null/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+CD28null 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. Highlights • Plaque rupture at OCT evaluation is associated to a specific adaptive immune system signature. • A deeper perturbation of adaptive immunity might be involved in fibrous cap thinning. • Molecular and morphological plaque phenotyping might be a new frontier for personalized medicine. [ABSTRACT FROM AUTHOR]

Abstract Background Percutaneous ventricular-assistance by Impella (IMP) represents an emerging strategy to manage patients with reduced left-ventricular (LV) ejection-fraction (EF) undergoing percutaneous-coronary-intervention (PCI). The hemodynamic behave during IMP-protected PCI has been scarcely investigated. Methods We reviewed the IMP console's function and hemodynamic data (which are continuously recorded during assistance) in a consecutive series of 37 patients who underwent elective IMP-protected PCI in two high-volume centers. All patients had multivessel disease and impaired LVEF. Coronary artery disease burden was graded using the British-Cardiovascular-Intervention-Society jeopardy-score (BCIS-JS) score. IMP motor speed and pressure signals (systolic blood pressure, SBP, and mean blood pressure, MBP) were analyzed. Primary hemodynamic end-points were "critical systolic blood pressure (SBP) drop" (SBP decrease ≥ 20 mm Hg reaching ≤90 mm Hg values) and "critical mean blood pressure (MBP) drop" (MBP decrease reaching ≤60 mm Hg). Results Over mean assistance duration of 254 ± 549 min, no IMP motor drop occurred. During PCI, SBP and MBP significantly decreased but all patients had SBP values >78 mm Hg. Critical SBP and MBP drops occurred in 10.8% of patients. Among all baseline and procedural characteristics, BCIS-JS was the only significant predictor of SBP drop (p = 0.001) while BCIS-JS and LV end-diastolic volume significantly predicted MBP drop (p = 0.001 for both). Conclusions In patients with reduced EF undergoing IMP-protected PCI, a significant pressure decrease occurs during PCI but pressure is systematically maintained at levels warranting vital organ perfusion. Critical pressure drops during PCI occur in some patients with higher jeopardized myocardium and left ventricular diastolic volumes. Highlights • During high-risk PCI no Impella malfunctioning occurred. • Throughout the procedure systolic and mean blood pressure significantly decreased. • Some patients experienced a major pressure drop. • Coronary anatomy complexity and left ventricle dimension could predict major pressure drop. [ABSTRACT FROM AUTHOR]

The clinical challenge of percutaneous coronary interventions (PCI) is highly dependent on the recognition of the coronary anatomy of each individual. The classic imaging modality used for PCI is angiography, but advanced imaging techniques that are routinely performed during PCI, like optical coherence tomography (OCT), may provide detailed knowledge of the pre-intervention vessel anatomy as well as the post-procedural assessment of the specific stent-to-vessel interactions. Computational fluid dynamics (CFD) is an emerging investigational tool in the setting of optimization of PCI results. In this study, an OCT-based reconstruction method was developed for the execution of CFD simulations of patient-specific coronary artery models which include the actual geometry of the implanted stent. The method was applied to a rigid phantom resembling a stented segment of the left anterior descending coronary artery. The segmentation algorithm was validated against manual segmentation. A strong correlation was found between automatic and manual segmentation of lumen in terms of area values. Similarity indices resulted >96% for the lumen segmentation and >77% for the stent strut segmentation. The 3D reconstruction achieved for the stented phantom was also assessed with the geometry provided by X-ray computed micro tomography scan, used as ground truth, and showed the incidence of distortion from catheter-based imaging techniques. The 3D reconstruction was successfully used to perform CFD analyses, demonstrating a great potential for patient-specific investigations. In conclusion, OCT may represent a reliable source for patient-specific CFD analyses which may be optimized using dedicated automatic segmentation algorithms. [ABSTRACT FROM AUTHOR]

Background Diffuse coronary artery disease treatment still remains a challenge for interventional cardiologists and cardiac surgeons. There are few data on full metal jacket (FMJ) stenting, especially with new-generation drug-eluting stents. We aimed to assess the efficacy and safety of FMJ with new-generation Zotarolimus-eluting stents (n-ZES). Methods and results All patients who underwent FMJ with n-ZES (≥ 60 mm stent length) in eleven Italian interventional centers participating in the Clinical Service® project were included in this analysis. The project population consisted of 120 patients and 122 lesions. Mean age was 67 ± 10 years and 95 (79.2%) patients were male. A chronic total occlusion was present in 34 lesions (27.9%). The number of stents implanted per lesion was 2.9 ± 0.8, and the diameter of the stents was 3.0 ± 0.5 mm. Predilation and post-dilatation were performed in 107 (87.7%) and 92 (75.4%) patients, respectively. At 41 ± 21 month follow-up there were 2 patients with subacute definite stent thrombosis, 6 patients (5.0%) had cardiac death and 5 patients (4.2%) had non-fatal myocardial infarction. Seven patients (5.8%) underwent clinically-driven target lesion revascularization. Fourteen patients (11.7%) had at least one major adverse cardiac event. Conclusion The treatment of diffuse coronary artery disease with FMJ stenting with n-ZES appears to be effective and safe. Late and very-late ST does not seem to be an issue and the rate of restenosis and of major cardiac adverse events after more than 3-year follow-up is rather low. [ABSTRACT FROM AUTHOR]

In this study, we aim to assess whether remote ischemic preconditioning (RIPC) reduces platelet activation during coronary angiography (CA) and/or percutaneous coronary interventions. We studied 30 patients who underwent CA because of a suspect of stable angina. Patients were randomized to RIPC (3 short episodes of forearm ischemia) or sham RIPC (controls) before the procedure. Blood samples were collected at baseline, at the end of the procedure, and 24 hours later. Monocyte-platelet aggregate (MPA) formation and platelet CD41 in the MPA gate and CD41 and CD62 expression in the platelet gate were assessed by flow cytometry, in the absence and in the presence of adenosine diphosphate (ADP) stimulation. A significant increase in platelet activation occurred during the invasive procedure in controls, which persisted at 24 hours. However, compared with controls, RIPC group showed no or a lower increase in platelet variables, including MPA formation (p <0.0001) and CD41 (p = 0.002) in the MPA gate and CD41 (p <0.0001) and CD62 (p = 0.002) in the platelet gate. ADP increased platelet activation at baseline, but did not further increase platelet reactivity during the invasive procedure in either groups. Percutaneous coronary interventions, performed in 10 patients (6 in the RIPC group and 4 in controls), did not have any further significant effect on platelet activation and reactivity compared with CA alone. In conclusion, RIPC reduces platelet activation occurring during CA. In contrast, no effects were observed on platelet response to ADP stimulation, probably related to the administration of an ADP antagonist in all patients. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to evaluate whether a strategy with a 600-mg clopidogrel load and a short-term, high-dose atorvastatin reload would improve outcomes in clopidogrel-naïve, statin-treated patients undergoing protected carotid stenting.Background: Optimal clopidogrel loading dose during carotid stenting has not been investigated; in addition, statin neuroprotection in this setting has not been described.Methods: A total of 156 patients were randomized using a 2 × 2 factorial design to receive either a 600-mg (n = 78) or 300-mg (n = 78) clopidogrel load given 6 h before intervention and either a atorvastatin reload (n = 76; 80 mg + 40 mg initiating 12 h before the procedure) or no statin reload (n = 80). The primary endpoint was the 30-day incidence of transient ischemic attack/stroke or new ischemic lesions on cerebral diffusion-weighted magnetic resonance imaging performed at 24 to 48 h.Results: Occurrence of the primary outcome measure was significantly lower in the 600-mg clopidogrel arm (18% vs. 35.9% in the 300-mg group; p = 0.019) and in the atorvastatin reload arm (18.4% vs. 35.0% in the no statin reload group; p = 0.031). High-dose clopidogrel also significantly reduced the transient ischemic attack/stroke rate at 30 days (0% vs. 9%, p = 0.02, secondary endpoint), without an increase in bleeding risk.Conclusions: In patients undergoing carotid stenting, a strategy using both a 600-mg clopidogrel load and a short-term reload with high-dose atorvastatin protects against early ischemic cerebral events. These results, obtained along with routine mechanical neuroprotection, provide new evidence of the optimization of drug therapy before percutaneous carotid intervention. (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting [ARMYDA-9 CAROTID]; NCT01572623). [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Platelets play a crucial role in the pathogenesis of acute coronary syndromes. Accordingly, previous studies showed increased platelet reactivity on admission in these patients. In this study we assessed platelet reactivity at short-medium term follow-up in patients with ST-segment elevation acute myocardial infarction (STEMI). Materials and methods: Fifty-nine patients (58±11years, 45 men), treated with primary angioplasty, were studied 1month after STEMI. Thirty-five patients were retested at 6months. Twenty matched patients with stable coronary artery disease served as controls. Platelet reactivity was assessed by flow cyometry at rest and at peak exercise, with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate. Results: Compared to controls, basal MPAs and CD41 in the MPA gate were higher in STEMI patients both at 1month (p=0.001 and p=0.002, respectively) and at 6months (p=0.03 and p=0.01, respectively). Basal CD41 and PAC-1 expression was also higher in STEMI patients at the two assessments compared to controls (P<0.001 for both). Exercise induced a similar increase in platelet reactivity in patients and controls. ADP induced a higher increase in CD41 platelet expression in STEMI patients compared to controls both at 1 and 6months (P<0.001). Conclusion: Platelet reactivity is increased in the first 6months after STEMI. The persistence of increased platelet reactivity in this time period may play a role in the early recurrence of coronary events after STEMI. [Copyright &y& Elsevier]

Abstract: Introduction: Previous studies showed differences in platelet reactivity in response to exercise in patients with syndrome X (SX) and those with obstructive coronary artery disease (CAD). In this study, we investigated whether similar differences could be detectable in response to a mental stressful stimulus. Materials and methods: We studied 30 SX patients (60±8 years, 8 men), 20 patients with stable angina and angiographically documented CAD (SA, 66±8 years, 14 men), and 11 patients with unstable angina (UA, 67±8 years, 6 men). A control group of 22 healthy controls (50±7 years, 5 men) was also studied. All subjects underwent a mathematical mental stress test (MST) consisting of rapid consecutive subtractions of number 7 for a period of 5 min. A venous blood sample was collected at baseline and immediately after MST. Platelet reactivity was measured on flowing blood as time necessary to occlude a ring coated with collagen–adenosine diphosphate (ADP; closure time, CT), using the platelet function analyzer (PFA-100) system. Results: At rest, CT was lower in UA patients (87±19 s) compared to controls (109±24 s, p=0.02) and SA patients (105±37 s, p=0.055), and also tended to be lower in SX patients (96±18 s) compared to controls (p=0.07). The CT response to MST differed significantly among groups (p=0.0009). At peak MST, CT did not change in controls (110±27 s, p=0.88), whereas it decreased in SA patients (96±29 s, p=0.003) and tended to decrease in UA patients (82±15 s, p=0.25). In contrast, a significant increase in CT with MST was shown in SX patients (103±21 s, p=0.007). Conclusions: Platelet reactivity is increased by MST in patients with CAD, whereas it paradoxically decreases in SX patients, which may constitute a protective effect against stress-induced events in these patients. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "EuroSCORE II versus additive and logistic EuroSCORE in patients undergoing percutaneous coronary intervention" by D. Capodanno and colleagues in the 2013 issue.