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(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Chronic coronary total occlusions (CTO) are considered an emerging predictor of ventricular arrhythmias (VAs), but currently there are few data on arrhythmic outcomes in patients affected by CTO undergoing radiofrequency catheter ablation of VAs. This study sought to evaluate the impact of unrevascularized CTO on the recurrence of VAs after catheter ablation. This was a single-center retrospective study enrolling 120 patients between 2015 and 2020. All patients were admitted for ventricular tachycardia (VT) or high premature ventricular contractions burden (>25% detected by Holter ECG), without evidence of acute coronary syndrome; they underwent coronary angiography, electrophysiology (EP) study, and three-dimensional electroanatomic mapping (3D-EAM) followed by VAs ablation. Twenty-eight patients (23%) of 120 patients showed CTO at coronary angiography. At baseline, the CTO group presented with higher prevalence of hypertension, chronic renal disease, systolic ventricular dysfunction, secondary prevention ICD implantation, and higher rate of LAVA by 3D-EAM compared with the non-CTO group. At a median follow-up of 15 months (range 1–96 months) after catheter ablation, the only independent predictor of VAs recurrence was the presence of moderate to severe left ventricular (LV) dysfunction. Therefore, the presence of CTO does not predict VAs recurrence after catheter ablation, which is instead predicted by LV dysfunction. [ABSTRACT FROM AUTHOR]

• Functional evaluation plays a key role to identify the mechanisms underlying myocardial ischemia also in patients with non-obstructive CAD. • Treatment of myocardial ischemia should be targeted to the underlying pathogenic mechanism, and for these reasons the use of an invasive functional approach may have important therapeutic implications. • Invasive functional assessment has important therapeutic and prognostic implications in patients with both acute and chronic coronary syndromes. [ABSTRACT FROM AUTHOR]

Macrophages play a key role in coronary plaque destabilization. In-vitro human monocyte-derived macrophages (MDMs) are used to study macrophages infiltrating tissue. Optical coherence tomography (OCT) provides an in-vivo insight of the coronary arteries. We compared the MDMs morpho-phenotype and culprit plaque features at OCT in acute coronary syndrome (ACS) patients according to the underlying plaque pathobiology. Sixty-six patients undergoing coronary angiography and pre-angioplasty OCT of the culprit vessel were allocated to three groups according to mechanism of ACS at OCT and C-reactive protein levels (cut-off: 2 mg/Ll): 1) plaque rupture with systemic inflammation; 2) plaque rupture without systemic inflammation, 3) plaque with intact fibrous cap. A blood sample was collected to obtain MDMs, categorized as having "round" or "spindle" morphology. Thirty-two patients (48.5%) were assigned to Group 1, 10 (15.2%) to Group 2 and 24 (36.4%) to Group 3. The "round" MDMs were significantly more frequent in Group 1 (39.25 ± 4.98%) than in Group 2 (23.89 ± 3.10%) and Group 3 (23.02 ± 7.89%), p = 0.008. MDMs in Group 1 as compared to Groups 2 and 3 showed lower efferocytosis (8.74 ± 1.38 vs 9.74 ± 2.15 vs 11.41 ± 2.41; p = 0.012), higher tissue factor levels (369.84 ± 101.13 vs 301.89 ± 59.78 vs 231.74 ± 111.47; p = 0.001) and higher heme oxygenase-1 expression (678.78 ± 145.43 vs 419.12 ± 74.44 vs 409.78 ± 64.33; p = 0.008). MDMs of ACS patients show morpho-phenotypic heterogeneity with prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation. Such MDMs subpopulation may take part to the cellular pathways leading to fibrous cap rupture with the subsequent thrombus formation. • Monocyte-derived macrophages to study macrophages infiltrating coronary plaques. • Optical Coherence Tomography to identify the mechanism of plaque destabilization. • Pro-thrombotic, oxidative macrophages are prevalent in ruptures with inflammation. [ABSTRACT FROM AUTHOR]

Patients with acute coronary syndrome (ACS) associated to high C-reactive protein (CRP) levels exhibit a higher risk of future acute ischemic events. Yet, the positive predictive value of CRP is too low to guide a specific treatment. Our study aims to identify a high-risk patient subset who might mostly benefit from anti-inflammatory treatment on the basis of the combination of optical coherence tomography (OCT) assessment of the culprit vessel and CRP serum levels. Patients admitted for ACS and undergoing pre-interventional OCT assessment of the culprit vessel were selected from "Agostino Gemelli" Hospital OCT Registry. The primary end-point was recurrent ACS (re-ACS). CRP levels ≥2 mg/L were considered abnormal. The overall study population consisted of 178 patients. Among these, 156 patients were included in the primary end-point analysis. The re-ACS rate was 23% at 3-year follow-up. High CRP (2.587, 95% CI:1.345–10.325, p = 0.031), plaque rupture (3.985, 95% CI:1.698–8.754, p = 0.009), macrophage infiltration (3.145, 95% CI:1.458–9.587, p = 0.012) and multifocal atherosclerosis (2.734, 95% CI:1.748–11.875, p = 0.042) were independent predictors of re-ACS. All patients (14/14) with high CRP and with all OCT high-risk features had re-ACS. At the other extreme, only 4 of the 82 patients with low CRP levels and lack of high-risk features at OCT examination exhibited re-ACS at follow-up. The combination of systemic evidence of inflammation and OCT findings in the culprit plaque identifies very high-risk ACS. Future studies are warranted to confirm these findings and to test an anti-inflammatory treatment in this patient subset. • High CRP and OCT features of the culprit vessel predict recurrent coronary events. • Patients with high-risk OCT features and high CRP experienced a recurrent ACS. • Our findings may contribute to individualize the secondary prevention of ACS. [ABSTRACT FROM AUTHOR]

Gender differences in the pathophysiology of atherosclerosis, cardiovascular risk factors, and diagnosis of coronary artery disease and valvular heart disease are well known. Such differences have also been outlined in the management and outcomes after acute coronary syndromes and valvular repair. Regarding the atherosclerotic process, pathological experimental studies suggest that plaque composition and burden may differ by gender. Female gender is associated with worse outcomes in the case of ischemic heart disease and, compared with men, women are less likely to undergo interventional cardiac procedures and sustain worse outcomes. In the setting of valvular heart disease (VHD), transcatheter aortic valve implantation (TAVI) and percutaneous edge-to-edge mitral valve repair are now well-established procedures with high success rates. In women with moderate to severe aortic stenosis, subgroup analyses in TAVI trials have demonstrated gender-related differences suggesting female gender as beneficial in terms of short-, mid-, and long-term outcomes. Similarly, several studies reported different procedural challenges and outcomes in males and females following surgical and percutaneous mitral valve repair. These diverse findings emphasize the necessity to provide gender-specific analyses of interventional methods. This review highlights gender differences in the epidemiology, pathophysiology, treatment options and clinical outcomes of the conditions mentioned above. • Gender differences in the pathophysiology and clinical presentation of coronary and valvular heart disease have been shown. • In the case of ischemic heart disease, females are less likely to receive timely and evidence-based treatment than males. • In female gender, percutaneous valvular interventions have shown similar (or even better) short- and long-term outcomes. • Further studies are necessary to investigate and solve open gender-related issues in contemporary interventional cardiology. [ABSTRACT FROM AUTHOR]

Introduction: Patients with atrial fibrillation (AF) receiving non-vitamin K oral anticoagulants (NOAC) have a slower decline in renal function than those taking warfarin. Moreover, a warfarin-related nephropathy has been described. Aim: We assessed variation of estimated glomerular filtration rate (eGFR) and occurrence of contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in patients with AF taking warfarin compared with NOAC. Material and methods: We retrospectively enrolled consecutive patients taking oral anticoagulation for AF undergoing PCI. The primary endpoint was variation in eGFR and serum creatinine levels within 48-72 h after PCI. The secondary endpoint was occurrence of CIN, defined as a ≥ 25% relative increase, or a ≥ 0.5 mg/dl absolute increase, in serum creatinine levels within 48-72 h. Results: We enrolled 420 patients (mean age: 75.0 ±5.5 years, 272 (64.7%) male), 124 (29.5%) treated with NOAC and 296 (70.5%) with warfarin. NOAC patients showed a reduced decline in renal function (eGFR change: -2.8 ±7.9 ml/min/1.73 m2 vs. -4.5 ±6.5 ml/min/1.73 m2, respectively, p = 0.02) and a smaller increase in serum creatinine levels (0.026 ±0.112 vs. 0.055 ±0.132, p = 0.032) after PCI compared with warfarin. In the multivariate linear regression model independent predictors of eGFR changes were diabetes, baseline eGFR ≤ 60 ml/min/1.73 m2 and warfarin use. Occurrence of CIN did not differ between NOAC and warfarin patients (13 (10.5%) vs. 46 (15.5%), p = 0.22). Conclusions: Patients with AF taking NOAC have a reduced decline in renal function after PCI compared with warfarin. The NOAC may be a reasonable option for patients with a high risk of developing CIN. [ABSTRACT FROM AUTHOR]

Abstract Background Over the last decade, the intra-coronary imaging (ICI) has emerged to guide percutaneous coronary intervention (PCI), thus overcoming the limitations of "luminology" offered by angiography. Methods In this review, we aim at purely focusing on the clinical implications of the employment of ICI in the routine practice, thus providing suggestions for future applications. In particular, we will describe the principal contributions and implications of ICI in the following different clinical settings: 1) assessment of clinical and imaging outcomes of PCI; 2) guiding PCI before and after stent implantation; 3) identification of mechanisms of stent failure. Results Several studies showed the capability of ICI in assessing the clinical and imaging outcomes of PCI. In particular, they have compared the ICI-guided PCI with the angiography-guided procedures, emphasizing the advantages of using imaging. Indeed, ICI can characterize the coronary plaque, provide a precise estimation of the coronary stenosis, select the appropriate method of intervention, and optimize stent deployment and lesion coverage. Finally, ICI has been shown to be useful to point out the mechanisms of stent failure. Conclusions. ICI can facilitate decision-making in patients with unclear angiographic findings, guide-selected interventions and optimize the final PCI results in complex lesions or. in high-risk patients. Finally, by the identification of specific mechanisms of stent failure, the ICI can allow to adopt a tailored therapy for the singles cases. Highlights • Intra-coronary imaging (ICI) allows to assess clinical and imaging outcomes; • ICI allows to characterize the coronary plaque; • ICI allows to optimize stent deployment; • ICI allows to identify the mechanisms of stent failure. [ABSTRACT FROM AUTHOR]

Inflammation is an important player both for the initiation and progression of coronary artery disease and for coronary plaque instability. Moreover, inflammation contributes to stent thrombosis and in-stent restenosis after percutaneous coronary intervention. In the past several decades, most studies evaluated the involvement of cellular effectors of classic inflammatory responses, such as monocytes/macrophages, neutrophils, and T cells. Yet, besides classic inflammation, mounting evidence derived from both experimental and clinical studies suggests an important, often unrecognized, role for effector cells of allergic inflammation in both the pathogenesis of coronary artery disease and adverse events following stent implantation. In this review, we discuss the role of effector cells of allergic inflammation in the setting of coronary artery disease progression and instability, and in the occurrence of adverse events following stent implantation, as well. Moreover, we discuss possible therapeutic approaches targeting different specific pathways of allergic inflammatory activation. [ABSTRACT FROM AUTHOR]

Persistence or recurrence of angina after successful percutaneous coronary intervention (PCI) represent an important clinical issue involving from one fifth to one third of patients undergoing myocardial revascularization at one-year follow-up. A systematic approach to this syndrome is strongly needed. Precision medicine is particularly important in addressing angina after successful PCI because of the multiple underlying causes. Restenosis or coronary atherosclerosis progression explain symptom recurrence after successful PCI in some patients, while functional causes, including vasomotor abnormalities of epicardial coronary arteries and/or coronary microvascular dysfunction, explain symptoms in the remaining patients. In this review, we summarize the mechanisms of persistent or recurrent angina after PCI, proposing a diagnostic algorithm and a systematic therapeutic approach. [ABSTRACT FROM AUTHOR]

Patients with an acute coronary syndrome (ACS) due to plaque rupture had a worse prognosis when compared with those without plaque rupture with a higher rate of target vessel revascularization and readmission for unstable angina, suggesting that both stent failure and disease progression occur more frequently. However, it is not known whether recurrent episodes of coronary instability in the same patient are caused by the same pathogenetic mechanism. Thus, we sought to investigate the mechanisms of coronary instability imaged by optical coherence tomography in patients with recurrent ACS events. The present case series, with 4 patients having recurrent ACS, shows that the same mechanism of coronary instability is present during both first and recurrent instability. This hypothesis-generating finding may support further studies targeted at assessing the mechanisms of coronary instability recurrence and how to tailor preventive measures to the underlying mechanism of instability. [ABSTRACT FROM AUTHOR]

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 > 12 h) 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 ± 11.72 years, 57 (73%) male; mean time of symptom onset 23.14 ± 16.06 h] with a mean follow-up time of 29.7 ± 14.1 months. 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. [ABSTRACT FROM AUTHOR]

Ivabradine is a heart rate reducing agent that exhibits anti-ischemic effects through the inhibition of funny electrical current in the sinus node resulting in heart rate reduction, thus enabling longer diastolic perfusion time, and reduced myocardial oxygen consumption without detrimental changes in arterial blood pressure, coronary vasomotion, and ventricular contractility. The current guideline-based clinical use of Ivabradine is reserved for patients with stable angina pectoris who cannot tolerate or whose symptoms are inadequately controlled with beta blockers. In patients with chronic heart failure and reduced ejection fraction, Ivabradine has demonstrated beneficial effects in improving clinical outcomes when added to conventional therapy. However, the role of Ivabradine in acute coronary syndromes has not been established. Based on the results from some relevant preclinical studies and a limited amount of clinical data that were reported recently, the role of Ivabradine in acute ischemic events warrants further investigation. The aim of this review is to provide an overview of the available literature on the potential role of Ivabradine in the clinical context of acute coronary syndromes. [ABSTRACT FROM AUTHOR]

Background: Bioresorbable coronary stents have been introduced into clinical practice to improve the outcomes of patients treated with percutaneous coronary intervention. The everolimus-eluting bioresorbable vascular scaffold (BVS) is the most studied of these stent platforms; however, recent trials comparing BVS with everolimus-eluting metallic stents (EES) raised concerns about BVS safety. We aimed to assess the efficacy and safety of BVS versus EES in patients undergoing percutaneous coronary intervention.Methods: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials, scientific sessions abstracts, and relevant Web sites for randomized trials with a follow-up of ≥2 years investigating percutaneous coronary interventions with BVS versus EES. The primary outcomes of our analysis were definite/probable stent thrombosis (ST) and target lesion failure (TLF; device-oriented composite end point of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization [TLR]). Secondary outcomes were target vessel myocardial infarction, TLR, and cardiac death. We calculated the risk estimates for main outcomes according to a fixed-effect model.Results: We included 7 trials comprising data for 5583 patients randomized to receive either a BVS (n=3261) or an EES (n=2322). Median follow-up was 24 months (range, 24-36 months). Patients treated with BVS had a higher risk of definite/probable ST compared with patients treated with EES (odds ratio, 3.33; 95% confidence interval, 1.97-5.62; P<0.00001). In particular, patients with BVS had a higher risk of subacute, late, and very late ST, whereas the risk of acute ST was similar. Patients treated with BVS compared with EES had a higher risk at 2 years of TLF (odds ratio, 1.47; 95% confidence interval, 1.14-1.90; P=0.003), driven mainly by an increased risk of target vessel myocardial infarction (odds ratio, 1.73; 95% confidence interval, 1.31-2.28; P=0.0001; I2=0%) and of TLR (odds ratio, 1.27; 95% confidence interval, 1.00-1.62; P=0.05). Of importance, the risk of TLF and TLR for patients with BVS was higher between 1 and 2 years, whereas there was no difference in the first year. Risk of cardiac death was similar between the 2 groups.Conclusions: Our meta-analysis of randomized trials with a follow-up of ≥2 years demonstrated a higher risk of ST and of TLF in patients treated with BVS compared with EES. Of note, BVS had a higher risk of subacute, late, and very late ST, whereas the risk of TLF and TLR was higher between 1 and 2 years. [ABSTRACT FROM AUTHOR]

Objectives: To compare angiographic and optical coherence tomography (OCT) data pertinent to thrombi, along with the histologic characteristics of aspirated thrombi in patients presenting with ST elevation myocardial infarction (STEMI) with or without inflammation, as assessed by C-reactive protein (CRP) and myeloperoxidase (MPO). Methods: In the OCTAVIA (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty) study, 140 patients with STEMI referred for primary percutaneous intervention were enrolled. The patients underwent OCT assessment of the culprit vessel, along with blood sampling of CRP and MPO, and histologic analysis of the thrombus. Results: Biomarkers were available for 129 patients, and histology and immunohistochemistry of the thrombi were available for 78 patients. Comparisons were made using the median thresholds of CRP and MPO (2.08 mg/L and 604.124 ng/mL, respectively). There was no correlation between CRP and MPO levels in the whole population (p = 0.685). Patients with high CRP levels had higher thrombus grades and more frequent TIMI flow 0/1 compared with those with low CRP levels (5 [1st quartile 3; 3rd quartile 5] vs. 3.5 mg/L [1; 5], p = 0.007, and 69.3 vs. 48.5%, p = 0.04, respectively). Patients with high MPO levels more commonly had early thrombi than had those with low MPO levels (42.5 vs. 20.0%, p = 0.04). Conclusions: CRP and MPO were not correlated in STEMI patients, possibly reflecting different pathogenic mechanisms, with CRP more related to thrombus burden and MPO to thrombus age. [ABSTRACT FROM AUTHOR]

Background: Natriuretic peptides are diagnostic/prognostic biomarkers in major cardiovascular diseases. We aimed at assessing the predictive role of N-terminal pro-A-type (NT-proANP) and pro-B-type (NT-proBNP) natriuretic peptides levels toward cardiovascular outcome in both stable and unstable coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in a non-primary PCI setting.Methods: A total of 395 patients undergoing PCI with stent implantation for either stable angina (SA) or non ST-elevation acute coronary syndrome (NSTE-ACS) were enrolled. Pre-procedural NT-proANP and NT-proBNP levels were measured. Occurrence of major adverse cardiac events (MACEs), composite of cardiac death, non-fatal myocardial infarction, and clinically driven target lesion revascularization (c-TLR), was the endpoint of the study. Follow up mean time was 48.53±14.69months.Results: MACEs occurred in forty-four patients (11%) during follow up. Both NT-proANP levels [3170 (2210-4630) vs 2283 (1314-3913) fmol/mL, p=0.004] and NT-proBNP levels [729 (356-1353) vs 511 (267-1006) fmol/mL, p=0.04] were significantly higher in patients with MACEs compared to patients without MACEs. Similar results were found when considering hard MACEs (myocardial infarction and cardiac death). NT-proANP levels were significantly higher in patients with c-TLR compared with patients without c-TLR [3705 (2766-5184) vs 2343 (1340-3960) fmol/mL, p=0.021]. At multivariate analysis, NT-proANP levels were a significant predictor of MACEs (HR 1.09, 95% CI 1.03-1.18, p=0.04). Kaplan-Meyer curves revealed that patients with elevated NT-proANP levels (>2.100fmol/mL) had a lower MACE free survival (p=0.003).Conclusions: Both NT-proANP and NT-proBNP levels were higher in CAD patients experiencing MACEs following PCI in a non-primary setting. Notably, only NT-proANP levels significantly affected prognosis after PCI. [ABSTRACT FROM AUTHOR]

Background Lipoprotein Lp(a) has been shown to be an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden in patients with ACS is largely unknown, as well as the association of Lp(a) with lipid rich plaques prone to rupture. Aim We aim at assessing CAD burden by coronary angiography and plaque features including thin cap fibroatheroma (TCFA) by optical coherence tomography (OCT) in consecutive patients presenting with acute coronary syndrome (ACS) and obstructive CAD along with serum Lp(a) levels. Methods This study comprises an angiographic and an OCT cohort. A total of 500 ACS patients (370 men, average age 66 ± 11) were enrolled for the angiographic cohort and 51 ACS patients (29 males, average age 65 ± 11) were enrolled for the OCT cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index. OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. Results In the angiographic cohort, at multivariate analysis, Lp(a) was a weak independent predictor of Sullivan score (p < 0.0001), stenosis score (p < 0.0001) and extent index (p < 0.0001). In the OCT cohort, patients with higher Lp(a) levels (≥30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (67% vs. 27%; P = 0.02), a wider lipid arc (135 ± 114 vs 59 ± 111; P = 0.03) and a higher prevalence of TCFA (38% vs. 10%; P = 0.04). Conclusions Among patients with ACS, raised Lp(a) levels are associated with an increased atherosclerotic burden and it identifies a subset of patients with features of high risk coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Restoring blood flow to ischemic but viable myocardium and reducing infarct size constitute the goals of reperfusion therapy with fibrinolytic drugs or primary percutaneous intervention in patients with ST-segment elevation myocardial infarction (STEMI). However, in a sizable proportion of patients, this intervention gains to reopen the obstructed epicardial coronary artery but does not achieve myocardial reperfusion because of coronary microvascular obstruction phenomenon (CMVO). In the last years, consistent evidence has pointed out how CMVO has a negative impact on outcome in patients with acute STEMI. Of note, most of the trials in this setting, mainly targeting reperfusion damage, have failed to show beneficial effects. In this article we provide a revision of mechanisms, diagnosis and prognosis of CMVO in acute STEMI, also pointing out the need of an integrated approach in order to prevent and treat CMVO in the different time windows of the acute event. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) is the unexpected death of an individual not attributable to an extracardiac cause, usually within 1 h of symptom onset (or within 24 h of last being seen in good health if the death is unwitnessed). SCD causes can be divided into structural, with coronary heart disease (CHD) as main player, and inherited arrhythmia syndromes, that account 1-- 2% of SCD in Western countries [[1]]. In conclusion, this study provides a relevant contribution in understanding SCD pathophysiological mechanisms, underlying the role of hypertension and inflammation. [Extracted from the article]

Aim : To assess eosinophil cationic protein (ECP) and C-reactive protein (CRP) serum levels at three time points according to different stent types. Methods : 54 patients (age 64 ± 10 years, male 78%), undergoing Bare Metal Stent (BMS) ( n = 11), mammalian Target Of Rapamycin (mTOR)-inhibitor DES ( n = 27) and mTOR-inhibitor bioabsorbable DES (BES) ( n = 16) implantation for stable angina (SA) or non-ST-elevation acute coronary syndromes (NSTE-ACS), were prospectively enrolled. ECP and CRP serum levels were assessed before revascularization, at 1-month and at 1-year after the procedure. Moreover, 21 patients found to have inducible ischemia or angina symptoms at 6 month-stress test underwent 1-year follow-up (FU) angiography. Results : Baseline and 1-month ECP levels were similar among the 3 groups, whilst 1-year ECP was significantly higher in m-TOR-DES [8.61 (6.55–19.77) μg/ml] compared with m-TOR-BES [2.03 (1.78–5.53) μg/ml] and BMS-treated patients [2.23 (1.45–8.95) μg/ml] ( p = 0.02), without significant difference between BES and BMS. CRP was similar among the 3 groups at all time points. 1-year ECP significantly correlated with late loss in patients undergoing FU angiography ( r = 0.64, p = 0.002), while CRP did not ( p = NS). Conclusions : Our finding suggests that mTOR-DES stent type is associated with an increase of ECP levels at 1-year, possibly reflecting a persistent eosinophil activation triggered by permanent polymer. [ABSTRACT FROM AUTHOR]

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 noneST 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 mg) hyperemia using a dual-sensoreequipped 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 L 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 adenosineeinduced hyperemia, leading to FFR underestimation. [ABSTRACT FROM AUTHOR]

Abstract: Post-mortem observations demonstrated that plaque fissure was the final event leading to coronary thrombosis and occlusion in about two-thirds of cases of sudden coronary death. Plaques prone to fissure have, therefore, been defined “vulnerable plaques” and are identified by specific anatomic features including thin inflamed fibrous cap, large lipidic core and positive remodeling. Accordingly, elegant imaging modalities have been developed in order to identify this “holy grail”. However, the results of prognostic studies based on the identification of vulnerable plaques have not been encouraging because of the low positive predictive value for major cardiovascular events. This observation is not surprising as the pathogenesis of acute coronary syndromes is complex and multifactorial. In this review we propose a pathogenetic classification of acute coronary syndromes in the attempt to identify homogeneous groups of patients with a common mechanism of coronary instability which can be identified by using specific biomarkers and imaging techniques, and become a specific therapeutic target. [Copyright &y& Elsevier]

Abstract: Summary: Drug eluting stents (DES) were introduced in clinical practice to overcome the problem of in-stent restenosis (ISR) that limited the overall efficacy of percutaneous coronary revascularization with bare metal stent (BMS). Long-term outcome data confirm a sustained benefit of DES as compared with BMS. However, this benefit is mainly evident in the first year of follow-up. Indeed, DES-related events may extend over this time, due to late events (late ISR and/or very late stent thrombosis). Prevention of late failure of DES may become a specific therapeutic target. [Copyright &y& Elsevier]

Background Parvovirus ( PV) B19 DNA is detected in endothelial cells and may cause endothelial dysfunction, which is involved in in-stent restenosis. We aimed at performing an exploratory analysis that evaluated if PVB19 DNA at the culprit coronary stenosis would be associated with an increased rate of major adverse cardiac events ( MACE) after coronary stenting. Materials and methods Consecutive patients undergoing stent implantation for stable or unstable coronary artery disease were enroled. Serology for PVB19 infection and presence of DNA for PVB19 on balloons used for predilatation were assessed in all patients. MACE rate, as a composite of cardiac death, myocardial infarction ( MI) or clinically driven target lesion revascularization ( TLR) was obtained at 24 month follow-up. Adjusted hazard ratio ( HR) with 95% confidence interval ( CI) was calculated for variables associated with MACE. Results One hundred and nine patients [age 66 ± 10, male sex 89 (82%)] were enroled. At 24-month follow-up, 18 patients experienced a MACE. Two patients (2%) experienced MI, while 16 patients (15%) experienced clinically driven TLR. At multiple Cox regression analysis, the presence of PVB19 DNA on the balloon and the use of bare-metal stents were independent predictors of MACE [ HR 3·30, 95% CI (1·12-10·08), P = 0·03 and HR 4·19, 95% CI (1·60-10·94), P = 0·003]. Conclusions PVB19 DNA detected on the balloon used for dilatation of coronary stenosis before stent implantation is associated with MACE rate at follow-up, mainly due to clinically driven TLR. The results of this exploratory analysis should be confirmed in a larger population. [ABSTRACT FROM AUTHOR]

Laser atherectomy might decrease procedural complications during percutaneous coronary intervention (PCI) of degenerated saphenous vein grafts (SVGs) in case of unstable or thrombotic lesions because of its ability to debulk and vaporize thrombus. We aimed at prospectively evaluating the safety and efficacy of excimer laser coronary angioplasty (ELCA) as a primary treatment strategy in consecutively unstable patients undergoing PCI of degenerated SVG lesions. Seventy-one consecutive patients with noneST elevation acute coronary syndrome (mean age 69 ± 10 years, 66 men [89%]) undergoing PCI of degenerated SVG were enrolled in a prospective case-control registry, using 2 different distal protection devices (DPDs; FilterWire EZ [Boston Scientific, Natick, Massachusetts; n = 24] and SpiderRX [Ev3, Plymouth, Minnesota; n = 23]) or ELCA (n = 24). Primary end points of the study were incidence of angiographic microvascular obstruction (Thrombolysis In Myocardial Infarction flow grade of <3 or Thrombolysis In Myocardial Infraction flow grade of 3 with myocardial blush grade 1 to 2) and incidence of type IVa myocardial infarction. Angiographic microvascular obstruction incidence tended to be less in ELCA-treated patients compared with DPD-treated patients (3 [13%] vs 15 [32%], p = 0.09). Type IVa myocardial infarction incidence was more in DPD-treated patients compared with ELCA-treated patients (23 [49%] vs 5 [21%], p = 0.04). In conclusion, in patients with noneST elevation acute coronary syndrome undergoing PCI of degenerated SVG, ELCA compared with DPD, is associated with a trend for better myocardial reperfusion and a lesser incidence of periprocedural necrosis. Controlled randomized trials are warranted to confirm these early observations. [ABSTRACT FROM AUTHOR]

The success rate of recanalization of coronary chronic total occlusion (CTO) has improved in recent years, but the clinical benefit associated with successful CTO recanalization in the drug-eluting stent (DES) era is not well known. A cohort of 317 consecutive patients (mean age 65 ± 10, 84% men) with CTOs (defined as Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 and duration >3 months) of native coronary vessels in which percutaneous coronary intervention was attempted was enrolled from June 2005 to March 2009. All successful procedures (196 patients) were performed by DES implantation. The incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and repeat revascularization) was assessed during a mean follow-up period of 3 years. MACE predictors were assessed in clinical, angiographic, and procedural data, including procedural success. Patients with successful percutaneous coronary intervention experienced a significantly lower MACE rate compared to those with failed procedures (17 [9%] vs 32 [26%], p = 0.008). Patients with multivessel disease experienced MACEs more frequently than those with single-vessel disease (45 [22%] vs 4 [4%], p = 0.002). On multiple Cox regression analysis, the presence of multivessel disease and CTO opening failure were independent predictors of MACEs (hazard ratio 2.31, 95% confidence interval 1.17 to 4.96, p = 0.01, and hazard ratio 1.81, 95% confidence interval 1.33 to 4.12, p = 0.02, respectively). The worst prognosis was confined to patients with multivessel disease and failed procedures (hazard ratio 2.73, 95% confidence interval 1.21 to 3.92, p = 0.03). In conclusion, successful recanalization of CTOs with DES translates into a reduction of the 3-year MACE rate compared to failed procedures, and the worst prognosis is observed in patients with failed procedures and multivessel disease, a notion that might be taken into account in the management of patients with coronary CTOs. [Copyright &y& Elsevier]

Abstract: Objective: Low density lipoproteins (LDL) with an electronegative charge [LDL(−)] may cause endothelial injury. We assessed the association between serum LDL(−) levels and coronary artery disease (CAD) severity. Methods: We prospectively enrolled patients with CAD angiographic evidence [stable angina (SA) or non-ST-elevation-acute coronary syndrome (NSTE-ACS)], or with normal coronary arteries (NCA). Baseline LDL(−) serum levels were measured in all patients. Angiographic CAD extent was assessed by using the Bogaty extent index, while CAD severity by evaluating the presence of multi-vessel disease. Results: Forty-seven patients (age 61 ± 9 years, male sex 60%) were enrolled (17 SA, 15 NSTE-ACS and 15 NCA patients). LDL(−) levels were significantly higher in SA [21% (18–34) p = 0.0001] and NSTE-ACS [22% (18–28), p = 0.0001] as compared to NCA [6% (5–8)], without significant differences between SA and NSTE-ACS (p = 0.92). Multi-vessel disease patients had higher LDL(−) levels as compared to single-vessel disease patients (p = 0.002) but similar total LDL levels (p = 0.66). LDL(−) significantly correlated with extent index (r = 0.38, p = 0.03), while total LDL did not (p = 0.24). Conclusion: LDL(−) serum levels are associated with CAD angiographic severity and extent. This exploratory analysis should prime further larger studies in order to assess LDL(−) proatherogenic role. [Copyright &y& Elsevier]

Angulated lesions have been shown to be associated with abrupt closure or periprocedural myocardial injury. In particular, when disease is present at the level of the angulated or bifurcated lesion, balloon dilatation may help in wire crossing but it may also cause branch occlusion. Several methods and devices have been described to manipulate coronary guidewires across angulated and bifurcated lesions. This case report describes a highly angulated coronary bifurcated lesion where, after the failure of multiple wires to cross the lesion toward the main branch, it was successfully crossed after excimer laser debulking, which facilitated the wire crossing into the main branch, without causing branch occlusion. (J Interven Cardiol 2011;24:514-517) [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2011; 41 (11): 1210-1219 Abstract Background In models of acute ischaemia, erythropoietin (EPO) administration has been found to attenuate vascular injury largely through reduced apoptosis, suppressed inflammation and increased nitric oxide availability. We studied the association between circulating endogenous EPO and no-reflow in patients with first ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods Blood sampling was performed before PPCI. Consecutive patients with ( n = 24) or without ( n = 24) evidence of angiographic no-reflow after PPCI were enrolled. Angiographic no-reflow was defined as Thrombolysis in Myocardial Infarction (TIMI) flow ≤ 2 or as TIMI flow = 3 but with myocardial blush grade < 2. We also assessed electrocardiographic (ECG) no-reflow as ≤ 50% resolution of maximal ST elevation 60 min after PPCI. Results Baseline characteristics did not correlate significantly with EPO concentrations. In contrast, both angiographic and ECG no-reflow correlated with lower EPO levels at univariate analysis [median (interquartile): 4·2 (0·6-9·5) vs. 12·2 (5·2-20·3) mIU mL−1, P = 0·001, and 4·0 (0·6-7·1) vs. 9·3 (1·0-12·6) mIU mL−1, P = 0·01, respectively]. At multivariable analysis, decreasing EPO tertiles and left anterior descending as the infarct-related artery were the only factors that predicted both angiographic and ECG no-reflow ( P = 0·017 and P = 0·02 for EPO; P < 0·005 and P > 0·05 for left anterior descending artery, respectively). Conclusions We found an independent, graded, inverse relation between endogenous EPO levels and angiographic and ECG no-reflow following PPCI. In animal models of ischaemia, EPO has been found to be protective. In humans, endogenous EPO may contribute to offset the mechanisms responsible for no-reflow. [ABSTRACT FROM AUTHOR]

Women affected by polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. We demonstrated that women with PCOS showed an expansion of CD4+CD28null T cells, an aggressive population of T lymphocytes that has been recently associated with recurrent coronary instability and type 2 diabetes mellitus. This sheds new light on possible mechanisms responsible for the higher rate of cardiovascular disease among women with PCOS. [ABSTRACT FROM AUTHOR]

Abstract: Objective: we assessed the association between baseline eosinophil cationic protein (ECP) levels, a sensitive marker of eosinophil activation, and clinical outcome in patients undergoing bare metal stent (BMS) implantation. Methods: basal ECP levels were measured in 110 patients (69±11 years, 88 men) undergoing BMS implantation. Major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, or clinically-driven target lesion revascularization, were registered at 24-month follow-up. Results: eighteen (16.4%) patients had MACEs and showed higher ECP levels compared with those without MACEs [20.1 (9.8–47.3) vs. 9.5 (5.0–27.2)g/L, p =0.02]. At follow-up, ECP level >11g/L was the only significant predictor of MACEs (HR 3.5, 95% CI 1.1–10.4, p =0.03). Conclusion: basal ECP levels are associated with MACEs after BMS implantation, suggesting that an allergic-mediated inflammation against the metal could explain some adverse reactions occurring after coronary stenting. [Copyright &y& Elsevier]

The main adverse reactions to coronary stents are in-stent restenosis (ISR) and stent thrombosis. Along with procedural factors, individual susceptibility to these events plays an important role. In particular, inflammatory status, as assessed by C-reactive protein levels, predicts the risk of ISR after bare-metal stent implantation, although it does not predict the risk of stent thrombosis. Conversely, C-reactive protein levels fail to predict the risk of ISR after drug-eluting stent (DES) implantation, although they appear to predict the risk of stent thrombosis. Of note, DES have abated ISR rates occurring in the classical 1-year window, but new concern is emerging regarding late restenosis and thrombosis. The pathogenesis of these late events seems to be related to delayed healing and allergic reactions to polymers, a process in which eosinophils seem to play an important role by enhancing restenosis and thrombosis. The identification of high-risk individuals based on biomarker assessment may be important for the management of patients receiving stent implantation. In this report, we review the evolving role of inflammatory biomarkers in predicting the risk of ISR and stent thrombosis. [ABSTRACT FROM AUTHOR]

Coronary thrombosis is the most frequent final event leading to an acute coronary syndrome. In approximately two-thirds of cases, the thrombus overlies a ruptured plaque, whereas in one-third of cases it overlies an intact plaque with superficial endothelial erosion, a finding showed initially by histopathological postmortem studies and more recently confirmed by in vivo optical coherence tomography imaging. Interestingly, recent observations suggest that mechanisms leading to plaque rupture or erosion are different. In fact, in a recent study, we showed that myeloperoxidase levels in peripheral blood and expression within thrombi overlying the culprit plaque are much higher in patients with plaque erosion than in those with plaque rupture. These observations suggest that innate immunity activation is likely to play a key role, in particular, in plaque erosion and might become a therapeutic target in this subset of patients. [ABSTRACT FROM AUTHOR]

No-reflow phenomenon occurs frequently during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and it has a strong negative impact on outcome. Prevention of no-reflow has to be defined as any attempt to prevent its occurrence prior to or during the recanalization procedure. Strategy of prevention may be pharmacological or device based. Among drugs, abciximab is indicated by European Society of Cardiology (ESC) guidelines for prevention of no-reflow (class of recommendation IIa and level of evidence B). Among devices used for preventing no-reflow, manual thrombus aspiration only has been associated with a reduction of no-reflow and lower mortality at follow-up and is currently indicated in the ESC guidelines (class IIa of recommendation and level B of evidence). Treatment of no-reflow has to be defined as any attempt to treat its occurrence after coronary recanalization. Strategy of treatment may be pharmacological or device based. Adenosine and verapamil are indicated by ESC guidelines for treatment of no-reflow (class of recommendation IIb and level of evidence B and C, respectively). Serial assessment of myocardial perfusion showed that in up to 50% of patients no-reflow is spontaneously reversible. This finding may open new scenarios, as mechanisms of reversibility may become future therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Coronary atherosclerosis is a chronic inflammatory disease, but different inflammatory biomarkers may reflect different phases of atherosclerotic plaque evolution. We aimed at assessing the role of eosinophil cationic protein (ECP), a sensitive marker of eosinophil activation, and C-reactive protein (CRP) in coronary artery disease (CAD). Methods and results: Consecutive anginal patients with angiographic evidence of CAD [stable angina (SA) or non-ST-elevation acute coronary syndrome (NSTE-ACS)], or with angiographically normal coronary arteries (NCA) were enrolled. The severity of CAD was graded according to Bogaty''s score and coronary lesion morphology was defined as smooth or complex. Baseline ECP and high sensitivity CRP were measured in all patients. Of 198 patients (64±10 years, male 74%), 91 had SA, 57 had NSTE-ACS and 50 had NCA. ECP levels were significantly higher in SA [30μg/L (13.8–46.9), p <0.001] and NSTE-ACS [21.8μg/L (5.5–46.3), p =0.016] compared to NCA [9.7μg/L (6.1–13.6)], without significant difference between SA and NSTE-ACS (p =0.45). CRP levels were significantly higher in NSTE-ACS [2.38mg/L (1.11–11.94)] compared to SA [1.48mg/L (0.82–2.83), p =0.03], and NCA [1.09mg/L (0.8–2.1), p <0.001], without significant difference between SA and NCA (p =0.20). The addition of ECP to main cardiovascular risk factors improved the area under the curve from 0.88 to 0.92, p =0.007 for the angiographic diagnosis of CAD; further addition of CRP increased the area to 0.94, p =0.014. At multiple linear regression analysis ECP levels independently predicted CAD severity (p =0.001), whereas CRP levels independently predicted lesion complexity (p =0.01). Conclusions: Our study shows that ECP is a marker of CAD and that different inflammatory biomarkers reflect different phases of atherosclerotic plaque evolution. [Copyright &y& Elsevier]

Myocardial no-reflow may negate the benefit of urgent coronary revascularization in patients with acute ST-elevation myocardial infarction (STEMI). Among its pathogenetic mechanisms, distal embolization is of prominent importance and several studies have shown that a high coronary thrombotic burden is associated with distal embolization. We aimed at assessing predictors of angiographic thrombus grade in patients undergoing primary percutaneous coronary intervention. Ninety-one patients (62 ± 12 years old, 79% men) presenting for a first STEMI and undergoing urgent coronary angiography within 12 hours from onset of symptoms were consecutively included in the study. Thrombus grade was evaluated by angiography according to the Gibson score and patients were allocated to the high thrombus grade (HTG; score 4 to 5) group or to the low thrombus grade (score 0 to 3) group. Variables predicting angiographic thrombus grade were assessed among clinical, angiographic, procedural, and laboratory data. Sixty-four patients (61 ± 12 years old, 78% men) presented with HTG, whereas 27 patients (63 ± 10 years old, 80% men) presented with low thrombus grade. Patients an HTG showed a significantly higher white blood cell count (12.5 ± 4.8 vs 10.5 ± 2.9, p = 0.015). Aspirin and β-blocker therapy before admission were less frequently taken in the HTG group (5% vs 26% and 7% vs 23%, respectively, p = 0.01 and p = 0.03). At multivariate analysis, lack of previous therapy with aspirin was the only independent predictor of an HTG (odds ratio 6.14, 95% confidence interval 1.09 to 34.67, p = 0.04). In conclusion, previous aspirin therapy is associated with a decrease in angiographic thrombus grade in patients with STEMI treated with primary percutaneous coronary intervention, thus further priming efforts for appropriate use of aspirin in primary prevention of a first STEMI. [Copyright &y& Elsevier]

Abstract: 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 &y& Elsevier]

In a variable proportion of patients presenting with ST-segment elevation myocardial infarction, ranging from 5% to 50%, primary percutaneous coronary intervention achieves epicardial coronary artery reperfusion but not myocardial reperfusion, a condition known as no-reflow. Of note, no-reflow is associated with a worse prognosis at follow-up. The phenomenon has a multifactorial pathogenesis including: distal embolization, ischemia-reperfusion injury, and individual predisposition of coronary microcirculation to injury. Moreover, it is spontaneously reversible in some patients, thus suggesting that it might be amenable to treatment also when we fail to prevent it. Several recent studies have shown that biomarkers and other easily available clinical parameters can predict the risk of no-reflow and can help in the assessment of the multiple mechanisms of the phenomenon. Several therapeutic strategies have been tested for the prevention and treatment of no-reflow. In particular, thrombus aspiration before stent implantation prevents distal embolization and has been recently shown to improve myocardial perfusion and clinical outcome as compared with the standard procedure. However, it is conceivable that the relevance of each pathogenetic component of no-reflow is different in different patients, thus explaining the occurrence of no-reflow despite the use of mechanical thrombus aspiration. Thus, in this review article, for the first time, we propose a personalized management of no-reflow on the basis of the assessment of the prevailing mechanisms of no-reflow operating in each patient. [Copyright &y& Elsevier]

Abstract: Background: Cytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori (H. pylori). The role of CagA antigen in coronary instability is unknown. We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue. Methods: In the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events. Results: The titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161±90RU/ml) compared to those with stable angina (83±59RU/ml p <0.02), NCA (47.3±29RU/ml p <0.01) and healthy controls (73±69 p <0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95% CI, 1.15–1.58, p =0.0003). Conclusions: Taken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques. [Copyright &y& Elsevier]

Abstract: Background: Previous studies have shown conflicting results about the relationship between baseline C-reactive protein (CRP) and restenosis after stenting with bare metal stent (BMS). Methods: We assessed the association between serum CRP and angiographic restenosis after BMS by meta-analysis. Studies that reported basal serum CRP levels, above a prespecified cutoff value, before BMS deployment were included. An inverse random weighted meta-analysis was performed by entering the logarithm of the odds ratio (OR) of angiographic restenosis with its standard error for each study. Results: Nine studies enrolling 2747 patients were selected. CRP threshold value was around 3 mg/l in three studies, 5 mg/l in four studies, and 6.98 and 10 mg/l in one study. Follow-up duration was 6.2±3.0 (mean±S.D.) months. Higher preprocedural CRP levels were a significant predictor of angiographic restenosis: OR 1.59, 95% confidence interval 1.21–2.07, P=.001. Heterogeneity was found: χ 2 14.47, P=.07; I 2=44.7%. Publication bias was also detected (P=.01, Egger''s test). A sensitivity analysis, after excluding each study in turn, confirmed the predictive value of higher CRP levels, in agreement with the results of the main analysis. Conclusions: Among patients with coronary artery disease, undergoing percutaneous coronary intervention with BMS, higher baseline CRP levels are associated with higher risk of angiographic restenosis. A targeted therapeutic approach to patients with high baseline CRP, based on statins, oral corticosteroids, or PPAR gamma agonists, or selective use of drug-eluting stents, aiming at abating the higher risk of in-stent restenosis should be considered. [Copyright &y& Elsevier]

Abstract: Objective: Cystatin C (Cys-C) is an accurate marker of renal function. Recent studies have shown that serum Cys-C levels predict the risk of cardiovascular events. The causes of this association, however, are largely unknown. Methods and results: Seventy consecutive patients (age 62±12, male sex 87%) undergoing coronary angiography because of typical chest pain and found to have coronary artery disease were included in the present study. Patients with abnormal creatinine-derived glomerular filtration rate (<90ml/min/1.73m2) were excluded in order to avoid the well-known effect of overt renal insufficiency on coronary atherosclerosis. Coronary angiography was evaluated by two expert angiographers who assessed disease severity and extent according to the Sullivan''s score and lesion morphology. In all patients, Cys-C and C-Reactive Protein (CRP) serum levels were measured on admission. Multivariable analysis was performed to assess independent predictors of angiographic measures. Diabetes was the only predictor of disease severity (p =0.005), while male sex (p =0.03), hypercholesterolemia (p =0.04), diabetes (p <0.0001) and Cys-C (p <0.0001) were independent predictors of disease extent. Independent predictors of smooth lesions were diabetes (p <0.001) and Cys-C (p =0.005). No correlation was found between Cys-C and CRP serum levels (p =0.6). Conclusion: Cys-C is associated with coronary atherosclerosis extent and a smooth lesion morphology. The long-term prognostic role of Cys-C might be accounted for by a greater atherosclerotic burden, a necessary substrate for plaque destabilization. [Copyright &y& Elsevier]

Abstract: Background: Previous studies have reported conflicting results on the association between C-reactive protein (CRP) and extent of atherosclerosis, suggesting that the association between CRP and outcome in patients with acute coronary syndromes is independent of coronary artery disease extent. We tested this hypothesis in a selected population of patients with unstable angina undergoing coronary angiography. Methods: Ninety-seven consecutive patients with unstable angina were enrolled in this single-centre study. All patients underwent coronary angiography. CRP was measured by an ultrasensitive nephelometric method. We also measured serum levels of soluble CD40 ligand by ELISA and plasma fibrinogen levels by use of the Clauss method. Atherosclerotic disease severity and extent were assessed by angiography using the Bogaty score. The extent index refers to the proportion of the coronary tree affected by detectable atheroma on angiography. The primary end-point at 6 months was a composite of: (a) death, (b) myocardial infarction, and (c) recurrence of unstable angina requiring hospitalization. Cardiac death was the secondary end-point. Results: No significant correlation was found between baseline CRP serum levels and angiographic measures of atherosclerotic disease severity and extent, whereas a trend for a significant correlation was found between soluble CD40 ligand and extent index (p =0.06). Diabetic patients exhibited a higher extent index compared to non-diabetic patients (0.94±0.1 versus 0.7±0.04, p =0.04). Predictors of primary end-point at both univariate and multivariate analysis were: extent index (p =0.04 and 0.04, respectively), CRP levels (p =0.05 and 0.02, respectively), and lack of revascularization (p =0.03 and 0.02, respectively). Fibrinogen levels were the only independent predictor of cardiac death at follow-up (p =0.04). Conclusion: In this study we demonstrate that in patients with unstable angina, CRP serum levels and coronary atherosclerosis are not correlated, but both are independently associated with a worse outcome at 6-month follow-up. [Copyright &y& Elsevier]

Objectives: This study sought to assess the effect of acute alcohol intake on ischemic preconditioning (IPC) in humans using the clinical model of 2 sequential balloon inflations during a percutaneous coronary intervention (PCI). Background: Ischemic preconditioning is the most potent form of endogenous myocardial protection from irreversible ischemic injury. Experimental observations suggest that acute ethanol administration might abolish IPC. Methods: We studied 30 consecutive patients (22 men, mean age 65 years) undergoing elective coronary angioplasty who were randomized to receive an oral dose of 40 g ethylic alcohol (administered as 149 ml of Gordon’s Gin) or 149 ml of water 30 min before PCI. Intracoronary electrocardiogram was continuously monitored to assess the greatest ST-segment elevation or depression from baseline. Results: In placebo-treated patients, the change of ST-segment shift during the second inflation was significantly smaller than that during the first inflation (19.3 ± 9.1 vs. 15.7 ± 8.7, p = 0.005). In contrast, in gin-treated patients, the change of ST-segment shift during the second inflation was significantly greater than that during the first inflation (18.7 ± 7.2 vs. 22 ± 10, p = 0.03). The group–inflation interaction for ST-segment changes was highly significant (p < 0.001). Conclusions: This randomized, prospective study in humans shows that administration of a moderate dose of ethanol abolishes IPC occurring during sequential episodes of myocardial ischemia and is associated with worsening ischemia. Based on our study, intake of moderate to high doses of alcoholic beverages should be avoided in patients at high risk of acute myocardial infarction. [Copyright &y& Elsevier]

Abstract: Background: Preprocedural C-reactive protein (CRP) serum levels have been shown to predict the recurrence of angina or major adverse cardiac events after percutaneous coronary intervention. Directional coronary atherectomy (DCA), by reducing residual plaque burden and restenosis, has been shown to improve clinical outcome after coronary stenting. Thus, we assessed the influence of preprocedural CRP serum levels on the recurrence of cardiac events after DCA followed by bare metal stent implantation. Methods: We enrolled 40 consecutive patients (34 males; 61±10 years old) with single-vessel disease who were undergoing DCA. In all patients, preprocedural CRP serum levels were measured by an ultrasensitive nephelometric method. The endpoint of the study was defined as the composite incidence of death, myocardial infarction, and recurrence of angina requiring repeat revascularization at 6-month follow-up. Results: CRP serum levels were a significant independent predictor of the composite endpoint at multiple regression analysis [odds ratio=1.69; 95% confidence interval (95% CI)=1.04–2.75; P=.033]. Patients with recurrence of cardiac events had CRP serum levels higher than those of patients not having events on follow-up [3.95 (2.2–5.7) vs. 2 (1.3–3.3); P=.05]. Conclusion: In conclusion, our study shows that baseline CRP serum levels predict cardiac events after coronary bare metal stenting despite plaque debulking with directional atherectomy. [Copyright &y& Elsevier]

Abstract: Background: Systemic inflammation is involved in several pathological cardiovascular processes. However, whether it plays a role in the no-reflow phenomenon occurring in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is unknown. Methods: We studies 60 consecutive patients (59.5±12 years, 82% males) with a first ST-segment elevation AMI, treated by primary or rescue PCI within 6 h of symptom onset. Angiographic indexes of no-reflow, evaluated at the end of the procedure, included coronary TIMI flow grading, corrected TIMI frame count (c-TFC) and myocardial blush grade (MBG). ECG indexes of no-reflow included the lack of ST segment resolution (defined as a reduction <50% of the measured ST-segment elevation at 90 min, compared to the admission ECG), as analyzed both in the single lead with the maximal ST elevation and in all leads showing ST elevation on admission. Patients were divided into two groups according to baseline high-sensitivity C-reactive protein (CRP) serum levels measured on admission: high CRP group (CRP>5 mg/L) and low CRP group (CRP<5 mg/L). Results: A similar prevalence of final TIMI flow<3 and MBG<3 was observed in patients with high and low CRP serum levels (30% vs. 12%, p =0.1, and 50% vs. 53%, p =1.0, respectively), and c-TFC was also similar in the two groups (26±4.5 vs. 24±6, p =0.5). Accordingly, the prevalence of lack of ST-segment resolution in the two groups was similar, both by the single-lead method (25% vs. 25%, p =1.0) and the multiple-lead method (29% vs. 19%, p =0.4). Conclusion: In this study we failed to demonstrate any significant association between CRP serum levels on admission and coronary no-reflow, as assessed by both angiographic and ECG parameters in AMI patients treated by successful primary or rescue PCI within 6 h of chest pain onset. [Copyright &y& Elsevier]