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Aim of the present study was to describe the left ventricular longitudinal strain (LS) in all myocardial layers in patients with severe aortic stenosis (AS), preserved left ventricular ejection fraction (LVEF) in different LV geometry and to compare LS analysis before and early after acute LV unloading provided by transcatheter aortic valve implantation (TAVI). 68 patients were enrolled. LS was measured from the endocardial layer (Endo-LS), epicardial layer (Epi-LS) and full thickness of myocardium (Transmural-LS) before and after TAVI. Patients were divided in two groups accordingly with relative wall thickness (RWT): concentric LV hypertrophy (cLVH) vs eccentric LV hypertrophy (eLVH). Less impaired values of LS at baseline were observed, in all layers, in patients with cLVHas compared to patients with eLVH (Endo-LS was - 13.2 ± 2 vs - 11.1±3 %, p = 0.041; Epi-LS was - 11.8 ± 1.8 vs - 9.9 ± 3 %, p = 0.043; Transmural-LS was - 12.3 ± 1.8 vs - 10.49 ± 3.3 %, p = 0.02, respectively). A significant improvement in endocardial LS (Endo-LS) after TAVI was detected only in cLVH(- 13 ± 2 vs - 14 ± 2, p = 0.011). Our findings documented that concentric LVH had better basal strain function and showed a better myocardial recovery after TAVI compared to eLVH.

Aims: In ST-segment-elevation myocardial infarction (STEMI), cardiovascular magnetic resonance (CMR) holds the potentiality to improve risk stratification in addition to Thrombolysis in Myocardial Infarction (TIMI) risk score. Nevertheless, the optimal timing for CMR after STEMI remains poorly defined. We aim at comparing the prognostic performance of three stratification strategies according to the timing of CMR after STEMI., Methods and Results: The population of this prospective registry-based study included 492 reperfused STEMI patients. All patients underwent post-reperfusion (median: 4 days post-STEMI) and follow-up (median: 4.8 months post-STEMI) CMR. Left ventricular (LV) volumes, function, infarct size, and microvascular obstruction extent were quantified. Primary endpoint was a composite of all-death and heart failure (HF) hospitalization. Baseline-to-follow-up percentage increase of LV end-diastolic (EDV; ΔLV-EDV) ≥20% or end-systolic volumes (ESV; ΔLV-ESV) ≥15% were tested against outcome. Three multivariate models were developed including TIMI risk score plus early post-STEMI (early-CMR) or follow-up CMR (deferred-CMR) or both CMRs parameters along with adverse LV remodelling (paired-CMRs). During a median follow-up of 8.3 years, the primary endpoint occurred in 84 patients (47 deaths; 37 HF hospitalizations). Early-CMR, deferred-CMR, and paired-CMR demonstrated similar predictive value for the primary endpoint (C-statistic: 0.726, 0.728, and 0.738, respectively; P = 0.663). ΔLV-EDV ≥20% or ΔLV-ESV ≥15% were unadjusted outcome predictors (hazard ratio: 2.020 and 2.032, respectively; P = 0.002 for both) but lost their predictive value when corrected for other covariates in paired-CMR model., Conclusion: In STEMI patients, early-, deferred-, or paired-CMR were equivalent stratification strategies for outcome prediction. Adverse LV remodelling parameters were not independent prognosticators., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: The aim of this study was to identify variables that are associated with the durability of percutaneous repair of secondary mitral regurgitation at 6-month follow-up., Methods and Results: Thirty-five consecutive patients with functional mitral regurgitation scheduled for MitraClip implant were enrolled. Left ventricular (LV) volumes and function and mitral valve characteristics were assessed before and immediately after MitraClip implantation using three-dimensional transesophageal echocardiography. Five patients with an unsuccessful procedure were excluded. The other patients were subdivided according to repair durability: group 1 with a durable repair (19 patients, 65%) and group 2 with significant mitral regurgitation recurrence (11 patients, 35%). At baseline, group 1 patients had smaller and more elliptical mitral valve annulus (1055 ± 241 vs. 1273 ± 359 mm, P = 0.02 and 125 ± 11 vs. 117 ± 16%, P = 0.02), a smaller left atrial volume (54.1 ± 26 vs. 71.5 ± 20 ml, P = 0.005) and lower systolic pulmonary artery pressure (38 ± 11 vs. 49 ± 12 mmHg, P = 0.03). Baseline LV end systolic volume had a linear correlation with the 3D annulus area (P = 0.048) and an inverse correlation with annulus ellipticity (P = 0.021). Group 1 patients showed an increase in annulus ellipticity after MitraClip (125 ± 17 vs. 141 ± 23%, P = 0.014)., Conclusion: Percutaneous mitral valve repair leads to a significant and stable mitral regurgitation reduction in a large number of patients. Annulus dimensions and remodeling as well as left atrial area and pulmonary hypertension seem to be associated with durability of the procedure.

Aims: The aim of this study was to describe incidence and determinants of left ventricular reverse remodelling (r-LVR) at 6 months follow-up after MitraClip implantation in patients with secondary severe mitral regurgitation (MR) and reduced left ventricular ejection fraction (LVEF)., Methods and Results: Forty-five patients, undergoing MitralClip implantation with low ejection fraction and high surgical risk were enrolled in this study. Three of them died before the scheduled 6 months follow-up period and one patient had cardiac surgery due to MitraClip detachment. All patients underwent transthoracic 2D and 3D echocardiography before and 6 months after the procedure. A significant MR severity reduction and an improvement in New York Heart Association (NYHA) class were detected in all patients. The study population was divided in two groups according to the presence of r-LVR (51%, n = 23 patients) or not (non-rLVR group, 18 patients). Non-significant differences in MR aetiology and number of clips implanted were found. Left ventricular reverse remodelling patients showed significant lower values of logistic EuroSCORE and STS score, left ventricular end-diastolic volume index (LVEDV/i), right ventricular end systolic area, and pulmonary artery systolic pressure (PASp) at baseline evaluation. At multivariable analysis, baseline PASp value resulted to be the only independent predictor of r-LVR [odds ratio 95% confidence interval 0.94 (0.89-0.99), P = 0.021]. In r-LVR patients, a significant improvement in LVEF and global longitudinal strain and a reduction in left atrial volume index were detected after 6 months, whereas in non-rLVR subgroup a significant increase in both LVEDV/i and left ventricular end-systolic volume index was observed at follow-up., Conclusion: Even if a reduction of MR was detected in all patients after MitralClip implant, our findings suggest that end-stage patients presenting with higher left ventricular volumes, logistic scores, and PASp may not benefit from the procedure at longer follow-up in terms of left ventricular function., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

MitraClip is a validated treatment for significant mitral regurgitation (MR) in high-risk patients. Aims of the study were to evaluate immediate changes in mitral valve (MV) geometry induced by MitraClip and correlations between baseline geometry and cardiac remodeling. Eighty patients who underwent MitraClip for primary (48%) or secondary (52%) MR were enrolled. Intraoperative transesophageal echocardiographic 3D images were acquired immediately before and after the procedure for MV annulus (MVA) morphology analysis. Transthoracic 3D echocardiography was performed preoperatively and at 6 months follow-up (6MFU). Patients were classified on the basis of MR reduction (ΔMR) at 6MFU as Optimal (ΔMR ≥ 2) or Suboptimal (ΔMR < 2). An optimal result was reached in 60 (75%) patients, whereas 20 subjects showed a ΔMR< 2 at 6MFU. The Optimal showed significantly smaller baseline MVA (antero-posterior diameter 4.05 ± 0.59 vs 4.43 ± 0.68 cm; anterolateral-posteromedial diameter 4.38 ± 0.56 vs 4.70 ± 0.73 cm; MVA circumference 14.1 ± 1.7 vs 15.1 ± 2.3 cm; and 3D area 14.8 ± 3.9 vs 17.4 ± 5.3 cm 2 ), lower sphericity index and nonplanar angle compared with Suboptimal. A value of antero-posterior diameter ≥4.44cm was identified (receiver-operating characteristic curve) as a possible cut-off for preoperative identification of Suboptimal patients. Postoperatively, MitraClip induced reduction of MVA flattening (nonplanar angle), sphericity index, and size (as expressed by antero-posterior diameter, MVA circumference and area). At 6MFU, the Optimal showed significant decrease in left ventricular volumes and pulmonary artery systolic pressure. In conclusion, MitraClip induces remarkable changes in MVA geometry and favorable left ventricular remodeling is detected in patients with optimal mid-term outcome; a preprocedural antero-posterior diameter <4.44cm seems to be a potential predictor of mid-term optimal result., (Copyright © 2018. Published by Elsevier Inc.)

Non-valvular atrial fibrillation (NVAF) increases the risk of stroke by three- to five-fold, especially in elderly patients, creating a huge burden on medical system as well as a negative impact on patients' lives. Balancing efficacy and bleeding risk is a challenge when considering anticoagulation therapy in elderly patients, because of their frequent high risk of both stroke and bleeding. Real world data reveal the underuse of anticoagulation in the elderly, especially due to physicians' fear of bleeding, often neglecting the thromboembolic risk. Care of elderly patients with NVAF is often complicated by factors including adherence, cognitive impairment, health literacy, risk of falling, adverse effects, involvement of caregivers, and patient-physician relationship. Therefore, shared decision making and conversations between clinicians and patients are crucial. In addition, elderly patients often suffer from multiple comorbidities, requiring multiple concomitant medications, with an increased risk of drug interactions. Four non-vitamin K antagonist oral anticoagulants, the so-called direct oral anticoagulants (DOACs) - dabigatran, rivaroxaban, apixaban and edoxaban - have been approved for reducing the risk of stroke and systemic embolism in patients with NVAF. Clinical trials and real-world data show the advantages of this class of drugs compared to conventional anticoagulation in the treatment of elderly patients with NVAF and identify subgroups of older patients who may be more suitable candidates for particular agents. However, there are conflicting opinions on the absolute benefit of DOACs use in elderly patients. A key factor to consider is that elderly patients frequently suffer from renal impairment and therefore dose adjustments according to creatinine clearance are mandatory for DOACs. As each DOAC comes with its own unique advantages and safety profile, a personalized case by case approach should be adopted to decide on the appropriate anticoagulation regimen for elderly patients after weighing the overall risks and benefits of therapy.

Objectives: This study sought to investigate whether early post-infarction cardiac magnetic resonance (CMR) parameters provide additional long-term prognostic value beyond traditional outcome predictors in ST-segment elevation myocardial infarction (STEMI) patients., Background: Long-term prognostic significance of CMR in STEMI patients has not been assessed yet., Methods: This was a longitudinal study from a multicenter registry that prospectively included STEMI patients undergoing CMR after infarction. Between May 2003 and August 2015, 810 revascularized STEMI patients were included. CMR was performed at a median of 4 days after STEMI. Infarct size, microvascular obstruction (MVO), and left ventricular (LV) volumes and function were measured. Primary endpoint was a composite of all death and decompensated heart failure (HF)., Results: During median follow-up of 5.5 years (range 1.0 to 13.1 years), primary endpoint occurred in 99 patients (39 deaths and 60 HF hospitalization). MVO was a strong predictor of the composite endpoint after correction for important clinical, CMR, and angiographic parameters, including age, LV systolic function, and infarct size. The independent prognostic value of MVO was confirmed in all multivariate models irrespective of whether it was included as a dichotomous (presence of MVO, hazard ratio [HR]: 1.985 to 1.995), continuous (MVO extent as % LV, HR: 1.095 to 1.097), or optimal cutoff value (MVO extent ≥2.6% of LV; HR: 3.185 to 3.199; p < 0.05 for all). MVO extent ≥2.6% of LV was a strong independent predictor of all death (HR: 2.055; 95% confidence interval: 1.076 to 3.925; p = 0.029) and HF hospitalization (HR: 5.999; 95% confidence interval: 3.251 to 11.069; p < 0.001). Finally, MVO extent ≥2.6% of LV provided incremental prognostic value over traditional outcome predictors (net reclassification improvement index: 0.16 to 0.30; p < 0.05 for all models)., Conclusions: Early post-infarction CMR-based MVO is a strong independent prognosticator in revascularized STEMI patients. Remarkably, MVO extent ≥2.6% of LV improved long-term risk stratification over traditional outcome predictors., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Contrast echocardiography is widely used in cardiology. It is applied to improve image quality, reader confidence and reproducibility both for assessing left ventricular (LV) structure and function at rest and for assessing global and regional function in stress echocardiography. The use of contrast in echocardiography has now extended beyond cardiac structure and function assessment to evaluation of perfusion both of the myocardium and of the intracardiac structures. Safety of contrast agents have now been addressed in large patient population and these studies clearly established its excellent safety profile. This document, based on clinical trials, randomized and multicentre studies and published clinical experience, has established clear recommendations for the use of contrast in various clinical conditions with evidence-based protocols., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aims: To investigate the influence of cardiovascular risk factors (CV-RFs) on infarct severity and post-infarction left ventricular (LV) remodelling in acutely reperfused ST-segment elevation myocardial infarction (STEMI) patients studied with cardiovascular magnetic resonance (CMR)., Methods and Results: Four-hundred seventy-one patients were included in the study. Baseline CMR was performed at 4 ± 1 days after STEMI to assess area-at-risk, infarct size (IS), myocardial salvage index (MSI), microvascular obstruction (MVO), intramyocardial haemorrhage (IMH), LV volumes, and function. Cardiovascular magnetic resonance was repeated 4 months after STEMI (n = 383) to assess adverse LV remodelling (increase of LV end-diastolic volume >20% between baseline and follow-up). Smoking was associated with IMH at baseline even after correction for other factors associated with ischaemia-reperfusion injury including MVO, IS, and MSI (OR: 2.17, 95% CI: 1.17-4.00, P = 0.01). Unexpectedly, smoking was an independent protective predictor against adverse LV remodelling (OR: 0.43, 95% CI: 0.24-0.77, P = 0.005), consistent with the 'smoker's paradox'. However, the presence of IMH at baseline abolished the paradoxical, beneficial effects of smoking with respect to IS, baseline LV function, and post-infarction LV remodelling. No association between other CV-RFs, infarct severity, or post-infarction LV remodelling was observed., Conclusion: In patients with reperfused STEMI, smoking is strongly and independently associated with IMH at baseline. Nonetheless, consistent with the 'smoker's paradox', smoking was an independent predictor of more favourable post-infarction LV remodelling. However, the paradoxical beneficial effects of smoking were lost in patients with IMH., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Thrombectomy during primary percutaneous coronary intervention (Th-PCI) improves myocardial reperfusion in the absence of significant changes, in the acute phase, in traditional two-dimensional (2D) echo indexes of left ventricular (LV) function. The aim of this study was to evaluate the potential of 2D speckle tracking echocardiography (2DSTE) analysis in assessing the efficacy of thrombectomy as compared to standard 2D echo and cardiac magnetic resonance (CMR) data., Methods: Two-dimensional speckle tracking echocardiography analysis was performed in 60 anterior ST-segment elevation myocardial infarction (STEMI) patients to assess global (GLS), segmental (SLS) and regional longitudinal strain (RLS). 2D echo and CMR were performed within 5 days after PCI. Patients were divided into 2 groups according to the different methods of reperfusion used: 28 pts Th-PCI and 32 pts standard PCI (S-PCI)., Results: Baseline clinical and angiographic characteristics, 2D echo, and DE-CMR data before and after PCI were similar in the 2 groups, except for microvascular obstruction (MVO), significantly lower (P = 0.001) in Th-PCI group. Conversely, GLS was significantly higher in Th-PCI group (P < 0.001), and in particular in the subset of patients without MVO (P = 0.012). RLS was also significantly higher in Th-PCI group (P = 0.001). GLS significantly correlates with infarct size, (R = 0.47; P = 0.03) and MVO (R = 0.69, P = 0.001). Finally, SLS was significantly lower in the DE segments (P < 0.001)., Conclusions: Patients treated with Th-PCI had a more preserved microvascular integrity resulting in a better myocardial longitudinal deformation. 2DSTE analysis adds significant information on the efficacy of thrombus aspiration as compared to standard echocardiography and it is closely related to the extent of microvascular damage., (© 2013, Wiley Periodicals, Inc.)

Purpose: The aim of this work was to compare the prevalence of right ventricle involvement in a population of patients with myocardial infarction as detected by cardiac magnetic resonance (CMR), clinical presentation, electrocardiographic (ECG) and echocardiographic criteria., Materials and Methods: A total of 97 consecutive patients, admitted to our institution for acute myocardial infarction, underwent a standard CMR examination within 5 days after the event. The presence of myocardial oedema and late enhancement of the right ventricle were compared to infarct location (anterior vs. inferior), clinical data, ECG, echocardiography results and other CMR findings. The results were analysed statistically using the Student's t test for independent samples and the K statistic., Results: Among the 97 patients included in the study, a diagnosis of right ventricular infarction was established in 12, 14 and 24 cases on the basis of the clinical data, the ECG and echocardiography, respectively. CMR demonstrated myocardial oedema and late enhancement of the right ventricle in 48 and 32 cases, respectively. The right ventricle was involved in 46 % of patients with inferior myocardial infarction (15/32) and in 30 % with anterior myocardial infarction (17/56), correlating to a worsening of both right and left ventricular performance (p = 0.001-0.05)., Conclusions: The right ventricle is frequently involved in myocardial infarction, correlating to a worse functional impairment of both ventricles and a worse prognosis. This finding, which is often underestimated by traditional cardiological tests, is well revealed by CMR, with potential clinical and therapeutic impact.

Aims: Previous studies have shown that prodromal angina (PA) occurs frequently in acute myocardial infarction (MI) patients. However, the potential benefits of PA on ischaemic myocardial damage remain unknown., Methods and Results: One-hundred and fifty-four patients with acute ST-segment elevation MI successfully treated with primary percutaneous coronary intervention (PPCI) were prospectively evaluated for new-onset PA in the week preceding infarction and other factors known to influence myocardial salvage. Cardiovascular magnetic resonance was performed 8 ± 3 days after MI for the assessment of area-at-risk (AAR), MI size, myocardial haemorrhage (MH), microvascular obstruction (MO), and myocardial salvage index (MSI). Patients with PA (n = 60) compared with those without PA (n = 94) showed similar AAR but significantly smaller MI size leading to larger MSI (0.53 ± 0.27 vs. 0.32 ± 0.26, P < 0.001). Additionally, patients with PA had lower incidence of MH (18 vs. 33%) and MO (22 vs. 46%) than non-PA patients (both P < 0.05). At univariate analysis, higher MSI was associated with new-onset PA, lower myocardial oxygen consumption before PPCI, shorter time-to-PPCI, and higher post-procedural TIMI flow-grade. Neither collateral circulation nor medications administered before PPCI were associated to MSI. After correction for other covariates by multivariate analysis, new-onset PA remained significantly associated with MSI (β-value: 0.352, P < 0.001)., Conclusion: In acute MI patients, new-onset PA is associated with higher MSI independent of others factors known to influence jeopardized myocardium, as well as with less microvascular damage.

Aims: There is conflicting evidence on the impact of gender on reperfusion after primary coronary angioplasty (PPCI), and on left ventricular (LV) remodelling (LVR). In a cohort of patients with reperfused ST elevation myocardial infarction (STEMI), gender-related differences on myocardial reperfusion, and sex-related differences on LVR were assessed by using a comprehensive cardiac magnetic resonance (CMR) approach., Methods and Results: In four tertiary referral centres, 283 (238 males and 45 females) consecutive STEMI patients, treated with PPCI within 12 h from symptoms onset underwent CMR 3 ± 2 days after STEMI and at 4-month follow-up. By CMR, the area at risk, infarct size (IS), microvascular obstruction (MVO), and myocardial salvage index (MSI) were assessed. Women were older than men (P = 0.014), more hypertensive (P < 0.001) and more frequently presented with pre-infarct angina (P = 0.018). An MSI extent was significantly higher (P = 0.013), IS was significantly smaller at both time points (acute P < 0.001, follow-up P < 0.001), and the MVO extent was significantly smaller (P < 0.001) in women. At multivariate analysis, Killip class and female sex were independently associated with a higher MSI (P = 0.02, P = 0.05, respectively). A similar incidence of LVR in both sexes was observed at follow-up (P = 0.808)., Conclusions: The better reperfusion pattern observed in women by CMR in our population of reperfused STEMI suggests sex-based differences exist. No gender differences were observed with respect to incidence of LV remodelling at the follow-up mainly occurring in the subset of patients with a larger IS.

Background: Despite several efforts using two-dimensional echocardiography and cardiac magnetic resonance in the diagnosis of left ventricular noncompaction (LVNC), there are no universally accepted diagnostic criteria. The aim of this study was to describe the extent of noncompacted myocardium using a new three-dimensional echocardiographic parameter., Methods: Seventeen patients with diagnoses of LVNC on the basis of two-dimensional echocardiographic and clinical criteria, 26 Olympic rowing athletes, and 49 healthy volunteers underwent three-dimensional echocardiography. By offline analysis, left ventricular volumes, mass, ejection fraction, and sphericity index were calculated. Trabeculated left ventricular volume (TLV) was calculated as the difference between left ventricular end-diastolic volume obtained including and excluding the trabeculae in the cavity contour. TLV was also normalized by left ventricular end-diastolic volume (TLV%)., Results: TLV and TLV% were significantly higher in patients with LVNC (33.7 ± 10.9 mL and 24 ± 7%) as opposed to controls (7.1 ± 2.2 mL, P < .001, and 6 ± 2%, P < .001, respectively) and athletes (8.0 ± 3.0 mL, P < .001, and 5 ± 2%, P < .001, respectively). In detail, on receiver operating characteristic curve analysis, optimal cutoff values of 15.8 mL for TLV and 12.8% for TLV% were determined for the identification of LVNC (area under the curve, 1.00; P < .001). Mild positive correlations of TLV and TLV% were found with sphericity index (r = 0.294, P = .004, and r = 0.301, P = .004, respectively), and mild negative correlations were found with ejection fraction (r = -0.454, P < .001, and r = -0.217, P = .038, respectively)., Conclusions: Because of high spatial resolution and accuracy in volumetric quantification, three-dimensional echocardiography allows accurate measurement of the extent of noncompacted myocardium and identification of patients with LVNC., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Intima-media thickness of the common carotid artery (CCA-IMT) is a validated marker of systemic atherosclerosis process. The aim of this study was to evaluate the association between coronary artery disease (CAD), left ventricular hypertrophy (LVH) and CCA-IMT, assessed by Radio Frequency-Quality Intima Media Thickness (RFQIMT) method, the next generation of IMT real-time measurement, based on the direct analysis of the radiofrequency signal and endowed with high accuracy and reproducibility in early detection of arterial wall thickness., Methods: 115 patients (76 men, mean age: 65.1 ± 12 years) referred to our department and shown significant (≥ 70% luminal obstruction) stenosis at least in one major epicardial coronary artery were studied. Coronary angiograms were divided for severity and extent of the disease: 79 patients (69%) had one, 24 patients (21%) two, 12 patients (10%) three major epicardial coronary arteries with ≥ 70% stenosis. All patients underwent echocardiography and carotid ultrasound examination, assessed by RF., Results: Dividing RFQIMT data in tertiles, dyslipidaemia (31 patients with IMT ≥ 1.20 mm vs 16 with IMT = 0.91-1.19 vs 25 with IMT ≤ 0.9, p = 0.004), LVMI (153.5 ± 20.6 g/m² in IMT ≥ 1.20 mm vs 131.2 ± 8.4 g/m² in IMT = 0.91-1.19 mm vs 114.3 ± 11.1 g/m² in IMT ≤ 0.9 mm, P < 0.001) and number of high stenosed coronary arteries (IMT ≥ 1.20 mm population more often showed three vessel diseases than IMT ≤ 0.90 mm one, P < 0.001) seemed to be significantly related to CCA-IMT increases. Furthermore, LVMI is positively related to IMT (r = 0.91; P < 0.001). In a multivariate regression model (R2 = 0.88), RFQIMT remained significantly associated with the dyslipidemia (regression coefficient ± standard error [SE]: 0.057 ± 0.023; p = 0.017), LVMI (regression coefficient ± SE: 0.01 ± 0.001; P < 0.0001) and number of damaged coronaries (regression coefficient ± SE: 0.0174 ± 0.028; P < 0.0001)., Conclusions: RFQIMT is a sophisticated method for carotid ultrasound evaluation. Its evaluation in patients with at least one important major epicardial coronary vessel stenosis would help the accuracy in the general assessment of the number of coronary lesions in these patients.

Aims: To assess the intricate relationship between myocardial infarction (MI) location and size and their reciprocal influences on post-infarction left ventricular (LV) remodelling., Methods and Results: A cohort of 260 reperfused ST-segment elevation MI patients was prospectively studied with cardiovascular magnetic resonance at 1 week (baseline) and 4 months (follow-up). Area at risk (AAR) and MI size were quantified by T2-weighted and late-gadolinium enhancement imaging, respectively. Adverse LV remodelling was defined as an increase in LV end-systolic volume ≥15% at follow-up. One hundred and twenty-seven (49%) patients had anterior MI and 133 (51%) patients had non-anterior MI. Although the degree of myocardial salvage was similar between groups (P = 0.74), anterior MI patients had larger AAR and MI size than non-anterior MI patients yielding worse regional and global LV function at baseline and follow-up. At univariable analysis, anterior MI was associated with increased risk of adverse LV remodelling (P = 0.017) and lower LV ejection fraction (EF) at follow-up (P = 0.001), but not when accounted for baseline MI size. Accordingly, at multivariable analysis, baseline MI size but not its location was an independent predictor of adverse LV remodelling (odds ratio = 1.061, P < 0.001) and EF at follow-up (β-coefficient = -0.255, P < 0.001)., Conclusion: Anterior MI patients experience more pronounced post-infarction LV remodelling and dysfunction than non-anterior MI patients due to a greater magnitude of irreversible ischaemic LV damage without any independent contribution of MI location.

Aims: Microvascular damage (MD) occurring soon after primary percutaneous coronary intervention (PPCI) may reverse or remain sustained within the first week after ST-elevation myocardial infarction (STEMI). We investigated the incidence, determinants, and long-term clinical relevance of MD reversal after PPCI., Methods and Results: Serial two-dimensional echocardiograms (2DE) and a myocardial contrast study were obtained within 24 h of PPCI (T1) and at pre-discharge (T2) in 110 successfully re-perfused STEMI patients. Six months 2DE and 2-year clinical follow-up were obtained. After PPCI myocardial re-perfusion was normal at T1 only in 40 patients (36%, 'normal reflow'), recovered at T2 in 33 (30%, 'reversible MD'), and remained abnormal in 37 (34%, 'sustained MD'). At follow-up, normal reflow and reversible MD were coupled with a significant reduction in the infarct area, decrease in cardiac volumes, and a slight non-significant improvement in systolic function. Conversely, in the sustained MD group, the infarct area did not change and cardiac volumes significantly increased with a parallel worsening in systolic function. By multivariate analysis, independent predictors of reversible MD were: absence of family history of coronary artery disease (CAD), younger age, shorter time to re-perfusion, and absence of diabetes. The 2-year combined events rate was significantly lower in reversible MD (log-rank test P= 0.03) compared with sustained MD patients., Conclusions: In STEMI patients treated according to the current guidelines, MD frequently occurs soon after re-perfusion but it is reversible in ~50% of cases and it is associated with a favourable functional and clinical outcome. Family history of CAD, aging, time to re-perfusion, and diabetes are independent predictors of MD reversibility.

Up till now ST-segment elevation myocardial infarction (STEMI) is an important clinical and epidemiological question because of its high incidence and death rate. In this light, intervention principles continue to be developed to reach a precise diagnosis and a fast transport of the patient towards adequate hospitals. As the only instrument able to modify the natural course of this disease is the early restoration of coronary flow in the myocardial ischemic area, we can understand that time to reperfusion is the driving parameter in defining sanitary and therapeutic ways aimed at facing up to this pathology in its acute phase and limiting the subsequent chronic disfunction. Recently, our group have published a paper demonstrating the fundamental importance of reperfusing the patient within 90 minutes from the onset of the AMI symptoms.The aim of this article is to give a state of art of the international literature about timing question in STEMI and to underline that from our results emerges the necessity of a critical revision of the actual guidelines in order to allow a real optimization and therapy of this pathology.

Erythropoietin (Epo) is a hematopoietic hormone produced mainly by the kidneys in response to hypoxia. Recent acquisitions in the fields of hematology, neurology, cardiology, and experimental medicine show cytoprotective, angiogenetic and antiinflammatory effects of Epo. Exogenous erythroPoietin in Acute Myocardial Infarction: New Outlook aNd Dose Association Study (EPAMINONDAS, EudraCTno. 200500485386) is one of four ongoing randomized controlled trials, each testing the effects of Epo in >or=100 patients with STEMI. EPAMINONDAS is a multicenter, prospective, double-blind, placebo-controlled, dose-finding study assessing intravenous moderate doses of human recombinant Epo (epoietin-alpha, 100 or 200 IU/kg/die) versus placebo, given on the first 3 days, in 102 patients with first ST-segment elevation myocardial infarction. Initial dosing is within 12 h of primary percutaneous coronary revascularization. The primary endpoint is infarct size, quantified by CK-MB time-concentration curve, left ventricular wall motion score index, and pattern of contrast-enhanced magnetic resonance imaging. Secondary endpoints are ischemic recurrences, ventricular remodelling, and safety events, assessed in-hospital and at 12 months' follow-up. The results of current phase II studies will help define the safety/efficacy profile of Epo for patients with STEMI.

This paper examines the evidence for contrast echocardiography, both for improving assessment of left ventricular structure and function compared with unenhanced echocardiography and for the identification of myocardial perfusion. Based on the evidence, recommendations are proposed for the clinical use of contrast echocardiography.

Aims: Few data are available on the extent and prognostic value of reverse left ventricular remodelling (r-LVR) after ST-elevation acute myocardial infarction (STEMI). We sought to evaluate incidence, major determinants, and long-term clinical significance of r-LVR in a group of STEMI patients treated with primary percutaneous coronary intervention (PPCI). In particular, the role of preserved microvascular flow within the infarct zone in inducing r-LVR has been investigated., Methods and Results: Serial echocardiograms (2DE) and myocardial contrast study were obtained within 24 h of coronary recanalization (T1) and at pre-discharge (T2) in 110 reperfused STEMI patients. Follow-up 2DE was scheduled after 6 months (T3). Two-year clinical follow-up was obtained. Reverse remodelling was defined as a reduction >10% in LV end-systolic volume (LVESV) at 6 months follow-up. r-LVR occurred in 39% of study population. At multivariable analysis, independent predictors of r-LVR were an effective microvascular reflow within the infarct zone, the in-hospital improvement of myocardial perfusion, an initial large LVESV, and a short time to reperfusion. Cox analysis identified r-LVR as the only independent predictor of 2-year event-free survival. Combined events rate was significantly higher among patients without compared to those with r-LVR (log-rank test P < 0.05)., Conclusion: r-LVR frequently occurs in STEMI patients treated with PPCI and it is an important predictor of favourable long-term outcome. A preserved microvascular perfusion within the infarct zone is the major determinant of r-LVR.

Aims: To determine if perfusion stress echocardiography (PSE) with Imagify (perflubutane polymer microspheres) is comparable to stress perfusion imaging using (99m)Tc single photon emission computed tomography (SPECT) for coronary artery disease (CAD) detection. PSE is a novel technique for evaluating myocardial perfusion. RAMP (real-time assessment of myocardial perfusion)-1 and -2 were international, Phase 3 trials that evaluated the ability of PSE with Imagify, to detect CAD., Methods and Results: Chronic, stable, chest pain patients (n=662) underwent Imagify PSE and gated SPECT imaging at rest and during dipyridamole stress. Independent blinded cardiologists [three PSE readers per trial, and four SPECT readers (one for RAMP-1, three for RAMP-2)] interpreted images. CAD was defined by quantitative coronary angiography or 90-day outcome with clinical review. Accuracy, sensitivity, and specificity were evaluated using non-inferiority analysis (one-sided alpha=0.025) compared with SPECT. SPECT results for RAMP-1 and -2 were: accuracy (70%, 67%), sensitivity (78%, 61%), and specificity (64%, 76%). Accuracy of all six PSE readers was non-inferior to SPECT (66-71%, P

Erythropoietin (Epo) is synthesized mainly under hypoxic conditions by renal and extrarenal tissues, including liver, spleen, brain, lung, bone marrow, and reproductive organs. Hypoxia abrogates the degradation of hypoxia-inducible factors (HIF)-1 and -2, that can then bind to the hypoxia response element within the Epo gene, activating its transcription. Receptors for Epo are expressed on cells known to synthesize Epo, but also on cardiomyocytes, cardiac fibroblasts, and endothelial, retinal, gastric, prostate and vascular smooth muscle cells. Epo-receptor binding triggers at least three intracellular signalling cascades: (1) janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5); (2) phosphatidylinositol-3 kinase (PI3K)/Akt, and (3) RAS/mitogen-activated protein kinase (MAPK). Epo also enhances nitric oxide (NO) bioavailability through endothelial NO synthase transcription and activation, and exerts antiapoptotic actions through Bcl-2 and Bcl-XL. NO is a powerful vasodilator, insulin-sensitizer, inhibitor of atherothrombosis and apoptosis, and essential for progenitor mobilization. This article is a concise review of recent advances regarding the molecular and cardiovascular effects of Epo.

Background: Recent data show that percutaneous coronary intervention (PCI) in patients with stable postthrombolytic ST-segment elevation myocardial infarction (STEMI) is better than no PCI or ischemia-guided PCI. These results still have to find a pathophysiologic explanation. We hypothesized that complete mechanical recanalization of infarct-related artery improves clinical benefits of thrombolysis as a result of more preserved and better perfused coronary microcirculation. To test this hypothesis, we studied a selected STEMI population presenting very early after symptom onset in whom successful infarct-related artery reperfusion was obtained by thrombolysis followed or not by elective PCI within 24 hours, and we compared these 2 groups with those underwent primary PCI., Methods: This study analyzed 96 patients with STEMI randomized within 3 hours from symptom onset to primary PCI (group A, n = 36), tenecteplase followed within 24 hours by PCI (group B, n = 30), or to tenecteplase alone (group C, n = 30). Microvascular perfusion was assessed by myocardial contrast echocardiography. Regional contrast score, endocardial length and area of contrast defect on day 2 (T1) and at predischarge (T2), left ventricular end-diastolic volume, regional wall motion score, extent of wall motion abnormalities, and ejection fraction at T1, T2, and at 3 months' follow-up were calculated., Results: Baseline clinical and angiographic characteristics were not statistically different between groups. The extent of microvascular damage and of myocardial salvage was similar in primary PCI-treated or in invasively treated patients after lytic administration. Conversely, group C patients, although treated very early with fibrinolytic therapy, showed higher extent of microvascular damage and infarct size and a more depressed left ventricular function after reperfusion and at follow-up., Conclusions: Our data suggest that early PCI after lysis is more effective in preserving myocardial perfusion and function than lysis alone and may be a helpful alternative when primary PCI is not available.

In this study, we investigated whether the ultrasound contrast agents Levovist or Sono Vue injected intravenously during mechanical ventilation effectively pass through the pulmonary circulation. With echocardiography, we measured the time for the contrast to pass through the lungs; and the intensity of right and left ventricular cavity opacification at four time points: during spontaneous breathing (baseline), 5 minutes after the beginning of mechanical ventilation, and 5 minutes and 30 minutes after extubation. Forty patients undergoing elective peripheral neurosurgical procedures were prospectively and randomly enrolled: 20 patients received intravenous Levovist 1 g and 20 patients received intravenous Sono Vue 1 mL, at the four predefined time points. After intravenous injection, both Levovist and Sono Vue effectively passed through the lungs and opacified the right and left ventricular cavities, at the four time points. Pulmonary transit times were similar and constant for the two contrast agents tested: 6 +/- 2 seconds at baseline, 5 +/- 2 seconds during mechanical ventilation, 7 +/- 2 seconds at 5 minutes and 6 +/- 2 seconds at 30 minutes after extubation with Levovist; and 6 +/- 4 seconds at baseline, 6 +/- 3 seconds during mechanical ventilation, 6 +/- 2 seconds at 5 minutes and 7 +/- 3 seconds at 30 minutes after extubation with Sono Vue. In all patients, each of the four contrast injections achieved high-grade right and left ventricular chamber opacification. In conclusion, both the ultrasound contrast agents tested in this study, Levovist and Sono Vue, after intravenous injection pass through the pulmonary circulation during mechanical ventilation. Ultrasound contrast agents with these characteristics are suitable for intraoperative organ perfusion studies, with intravenous injection.

After many years of study and research, the noninvasive assessment of myocardial perfusion by echo contrast agents is becoming a clinical reality. The fast technological progress of echocardiographic imaging and the approval for human use in Europe and the United States of some first and second generation contrast agents explains the growing interest in this new methodology. Recently, a new second generation contrast agent, SonoVue, made of microbubbles stabilized by phospholipids and containing sulphur hexafluoride, has been introduced on the European market. We describe the role of intravenous myocardial contrast echocardiography with second-generation contrast agents such as SonoVue in the tailored reperfusion strategies in acute myocardial infarction.