The Effects of Granulocyte Colony-Stimulating Factor in Patients with a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling: A 10-Year Follow-Up of the RIGENERA Study.

BACKGROUND: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. METHODS: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. RESULTS: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 ± 4 years vs. 12 ± 4 years, p = 0.046. No difference was found in the incidence of major adverse events. CONCLUSIONS: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment.

Stent malapposition, strut coverage and atherothrombotic prolapse after percutaneous coronary interventions in ST-segment elevation myocardial infarction.

AIMS: Stent implantation in ST-segment elevation myocardial infarction (STEMI) patients can be challenging and sometimes associated with immediate and long-term suboptimal results. Stent malapposition and strut uncoverage, predictors of stent thrombosis, are frequently detected in STEMI patients at medium/long-term follow-up. Nevertheless, data at a short follow-up are missing. We aimed to assess the extent of stent malapposition and struts coverage in the subacute phase of STEMI after stent implantation in primary or rescue percutaneous coronary intervention (PCI). METHODS: STEMI patients undergone primary or rescue PCI and scheduled for a second coronary angiography after 2-7 days were enrolled. During the second procedure, frequency domain optical coherence tomography (FD-OCT) was performed to assess percentage of malapposed struts (MS%), percentage area of malapposition (MA%), percentage of uncovered struts (US%), percentage area of atherothrombotic prolapse (PA%) and optical coherence tomography thrombus score (OCT-TS). RESULTS: Twenty patients were included and 21 stents (19 865 struts) were evaluated. Strut uncoverage was relatively limited [US% = 11.1 (8.1-13.6) %]. Stent malapposition was observed frequently, even if at low degree [MS% = 6.4 (3.3-13.3) %, MA% = 1.80 (0.46-2.76) %] as well as atherothrombotic prolapse [PA% = 0.09 (0.00-1.06) %]. Both MA% and PA% were significantly related to residual OCT-TS (R = -0.52, P = 0.02 and R = 0.71, P < 0.001, respectively), use of thrombolysis (P = 0.001 and P = 0.004, respectively) and time elapsed from PCI to FD-OCT analysis (P = 0.001). CONCLUSION: In the subacute phase after stenting in STEMI patients, strut uncoverage is relatively limited, while stent malapposition and atherothrombotic prolapse are common albeit limited features. Residual thrombus burden influences the degree of both stent malapposition and atherothrombotic prolapse.

Presence of 'ghosts' and mortality after transvenous lead extraction.

AIMS: The number of cardiovascular implantable electronic devices has increased progressively, leading to an increased need for transvenous lead extraction (TLE) due to device infections. Previous studies described 'ghost' as a post-removal, new, tubular, mobile mass detected by echocardiography following the lead's intracardiac route in the right-sided heart chambers, associated with diagnosis of cardiac device-related infective endocarditis. We aimed to analyse the association between 'ghosts' assessed by transesophageal echocardiography (TEE) and intracardiac echocardiography (ICE) and mortality in patients undergoing TLE. METHODS AND RESULTS: We prospectively enrolled 217 patients (70 ± 13 years; 164 males) undergoing TLE for systemic infection (139), local device infection (67), and lead malfunction (11). All patients underwent TEE before and 48 h after TLE and ICE during TLE. Patients were allocated to two groups: either with (Group 1) or without (Group 2) post-procedural 'ghost'. Mid-term clinical follow-up was obtained in all patients (11 months, IQR 1-34 months). We identified 30 (14%) patients with 'ghost', after TLE. The significant predictors of 'ghost' were Charlson co-morbidity index (HR = 1.24, 95% CI 1.04-1.48, P = 0.03) and diagnosis of endocarditis assessed by ICE (HR = 1.82, 95% CI 1.01-3.29, P = 0.04). Mortality was higher in Group 1 than in Group 2 (28 vs. 5%; log-rank P < 0.001). Independent predictors of mid-term mortality were the presence of 'ghost' and systemic infection as the clinical presentation of device infection (HR = 3.47, 95% CI 1.18-10.18, P = 0.002; HR = 3.39, 95% CI 1.15-9.95, P = 0.001, respectively). CONCLUSION: The presence of 'ghost' could be an independent predictor of mortality after TLE, thus identifying a subgroup of patients who need closer clinical surveillance to promptly detect any complications.

The combined effect of subcutaneous granulocyte- colony stimulating factor and myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride on post-infarction left ventricular function, the RIGENERA 2.0 trial: study protocol for a randomized controlled trial.

BACKGROUND: Several clinical trials and recent meta-analyses have demonstrated that administration of recombinant human granulocyte-colony stimulating factor (G-CSF) is safe and, only in patients with large acute myocardial infarction (AMI), is associated with an improvement in left ventricular ejection fraction. Moreover, the mobilization and engraftment of the bone marrow-derived cells may differ significantly among patients, interfering with the restoration of left ventricular function after treatment. Therefore, the clinical potential application of the G-CSF has not yet been fully elucidated. METHODS/DESIGN: The RIGENERA 2.0 trial is a multicenter, phase II, placebo-controlled, randomized, open-label, with blinded evaluation of endpoints (PROBE) trial in which 120 patients with an acute ST-elevation myocardial infarction (STEMI) undergoing successful revascularization but with residual myocardial dysfunction will be enrolled. In cases where there is a left ventricular ejection fraction (LVEF) ≤ 45% the patient will be electronically randomized (1:1 ratio) to receive either subcutaneous recombinant human G-CSF (group 1) or placebo (group 2) both added on top of optimal standard of care. Both groups will undergo myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride (MCE) whilst undergoing the echocardiogram. The primary efficacy endpoint is the evaluation of the LVEF at 6 months after AMI assessed by cardiac magnetic resonance. Secondary efficacy endpoints are the evaluation of LVEF at 6 months after AMI assessed by echocardiography, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) assessed by cardiac magnetic resonance and echocardiography at 6 months, together with the incidence of major adverse clinical events (MACE) defined as death, myocardial infarction, sustained cardiac arrhythmias, cardiogenic shock, stroke and re-hospitalization due to heart failure at 1 year. DISCUSSION: The RIGENERA 2.0 trial will test whether G-CSF administration and MCE, through the enhancement of the bone marrow-derived cells homing in the myocardium, determines an improvement in regional and global contractile function, myocardial perfusion and infarct extension in patients with large AMI. The results of the present study are expected to envision routine clinical use of this safe, affordable and reproducible approach in patients with successful revascularization after AMI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02502747 (29 June 2015); EudraCT: 2015-002189-21 (10 July 2015).

Outcome of Patients Treated by Cardiac Resynchronization Therapy Using a Quadripolar Left Ventricular Lead.

BACKGROUND: Not all heart failure (HF) patients benefit from cardiac resynchronization therapy (CRT). We assessed whether choosing the site of left ventricular (LV) pacing by a quadripolar lead may improve response to CRT. METHODS AND RESULTS: We prospectively randomized 23 patients with HF (67±11 years; 21 males) to CRT with a quadripolar LV lead (group 1, with the LV pacing site chosen on the basis of QRS shortening using simultaneous biventricular pacing), and 20 patients (71±6 years; 16 males) to a bipolar LV lead (group 2, with devices programmed with a conventional tip-to-ring configuration). New York Heart Association (NYHA) class and LV ejection fraction (EF) by 2D echocardiography were assessed at baseline and after 3 months. The baseline EF was not different between the 2 groups (25±6% group 1 vs. 27±3% group 2; P=0.22), but after 3 months EF was higher in group 1 (35±13% group 1 vs. 31±4% group 2; P<0.001). A reduction in at least 1 NYHA class at 3 months was observed in 22 (96%) and 12 (60%) of group 1 and group 2 patients, respectively (P<0.05). CONCLUSIONS: CRT with a quadripolar LV lead was associated with an improvement of EF greater than that observed in patients receiving a bipolar LV lead. In devices with a quadripolar lead, CRT programming based on the best QRS shortening is reliable and effective. (Circ J 2016; 80: 613-618).

Efficacy of contrast medium induced Pd/Pa ratio in predicting functional significance of intermediate coronary artery stenosis assessed by fractional flow reserve: insights from the RINASCI study.

AIMS: The need of adenosine administration for the achievement of maximal hyperaemia limits the widespread application of fractional flow reserve (FFR) in the real world. We hypothesised that Pd/Pa ratio registered during submaximal reactive hyperaemia induced by conventional non-ionic radiographic contrast medium (contrast medium induced Pd/Pa ratio: CMR) can be sufficient for the assessment of physiological severity of stenosis in the vast majority of cases. The aim of the present study was to test the accuracy of CMR in comparison to FFR. METHODS AND RESULTS: Eighty patients with 104 intermediate coronary stenoses were prospectively and consecutively enrolled. CMR was obtained after intracoronary injection of 6 ml of radiographic contrast medium, while FFR was measured after administration of adenosine. Despite the fact that CMR values were significantly higher than FFR values (0.88 [IR 0.80-0.92] vs. 0.87 [IR 0.83-0.94], p<0.001), a strong correlation between CMR and FFR values was observed (r=0.94, p<0.001) with a close agreement at Bland-Altman analysis (95% CI of disagreement: -0.029 to 0.072). ROC curve analysis showed an excellent accuracy of CMR cut-off of ≤0.83 in predicting FFR value ≤0.80 (AUC 0.97 [95% CI: 0.91-0.99, specificity 96.1, sensitivity 85.7]). Moreover, no FFR value ≤0.80 corresponded to a CMR ≥0.88. CONCLUSIONS: CMR is accurate in predicting the functional significance of coronary stenosis. This could allow limiting the use of adenosine to obtain FFR to doubtful cases. In particular, we suggest considering a CMR value ≤0.83 to be significant, a CMR value ≥0.88 as not significant, and inducing maximal hyperaemia using adenosine for FFR assessment when CMR is between 0.84 and 0.87.

Safety of transvenous lead extraction according to centre volume: a systematic review and meta-analysis.

BACKGROUND: Transvenous lead extraction (TLE) is a complex invasive procedure and the experience of the operator and the team is a major determinant of procedural outcomes. AIM: Because of very limited data available on minimum procedural volumes to enable training and ongoing competency for TLEs, we performed a meta-analysis aimed at assessing the outcomes of TLE in the centres with low, medium, and high volume of procedures. METHODS: Of the 280 papers initially retrieved until February 2013, 66 observational studies met inclusion criteria and were included in at least one stratified meta-analysis: 17 were prospective studies; 47 had a retrospective design; and 2 were defined 'experience studies'. We included only articles published after the introduction of laser technique (year 1999). We divided the studies in low, medium, and high volume centres utilizing either the European Heart Rhythm Association (EHRA) or Lexicon classification criteria. RESULTS: When meta-analyses were carried out separately for the studies with larger and smaller sample sizes, either using EHRA or Lexicon classification criteria, no clear differences emerged in the combined rate of major complications or intraoperative deaths. In contrast, both minor complications and mortality at 30 days decreased as centre volume increased. CONCLUSIONS: In our meta-analysis of observational studies, patients who have been treated in higher volume centres have a lower probability of minor complications and death at 30 days regardless of the infection rate, length of lead duration, type of device, and type of extraction.

Predictors of postoperative atrial fibrillation in patients with coronary artery disease undergoing cardiopulmonary bypass: a possible role for myocardial ischemia and atrial inflammation.

OBJECTIVE: To evaluate the preoperative presence of C-reactive protein (CRP) and troponin T(hs-TnT) in patients with coronary artery disease (CAD) undergoing cardiopulmonary bypass (CPB) in order to better clarify the role of atrial inflammation and/or myocardial ischemia in the development of postoperative atrial fibrillation (POAF). DESIGN: Prospective, nonrandomized study. SETTING: University hospital. PARTICIPANTS: Thirty-eight consecutive ischemic patients admitted to the authors' hospital for CAD undergoing elective on-pump coronary artery bypass grafting (CABG). INTERVENTION: Elective on-pump CABG. MEASUREMENTS AND MAIN RESULTS: Peripheral blood samples were collected from all patients before and 24 hours after CABG to assess high sensitive (hs)-CRP and troponin T (hs-TnT) levels. The patients' heart rhythm was monitored by continuous ECG telemetry. Biopsies from the right atrial appendage were obtained at the beginning of the CABG procedure in order to perform immunohistochemistry for CRP and reverse transcription polymerase chain reaction for CRP mRNA expression. Fourteen patients out of 38 (36%) developed POAF. Atrial CRP was found in 31 patients (82%), 10 with POAF and 21 with sinus rhythm (71% v 87% respectively, p = ns). None of the atrial samples was positive for CRP mRNA. Atrial CRP did not correlate with serum hs-CRP levels and with occurrence of POAF, but with the incidence of diabetes (p = 0.010). Postoperative hs-TnT levels, but not hs-CRP levels, were identified as the only predictor of POAF occurrence (p = 0.016). CONCLUSIONS: In patients undergoing CABG, neither peripheral nor tissue preoperative CRP levels, but only postoperative hs-TnT levels, correlated with POAF, suggesting the primary role of an ischemic trigger of atrial fibrillation.

Influence of the amount of myocardium subtended by a stenosis on fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) specifically relates to the severity of a stenosis to the mass of tissue to be perfused. Accordingly, the larger the territory to be perfused, the greater the flow and the pressure gradient induced by maximal hyperemia. Although this notion may be considered intuitive, its unequivocal demonstration is still lacking. The aim of our study was to evaluate the influence of the amount of myocardium subtended to an intermediate stenosis on FFR, especially in relation to quantitative coronary angiography. METHODS AND RESULTS: The severity of each lesion was assessed by FFR and 2-dimensional quantitative coronary angiography. The amount of jeopardized myocardium was evaluated using 3 validated scores specifically adapted to this aim: the Duke Jeopardy Score (DJS), the Myocardial Jeopardy Index (MJI), and the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) Lesion Score (ALS). The presence of a concomitant collateralized chronic total occlusion was also reported. A total of 213 intermediate coronary stenoses in 184 patients were enrolled. FFR values were correlated to minimal lumen diameter (r=0.34; P<0.0001) and diameter stenosis (r=-0.28; P<0.0001). FFR was inversely correlated with DJS, MJI, and ALS (r=-0.28, P<0.0001; r=-0.40, P<0.0001; and r=-0.34, P<0.0001). Lesions localized on proximal left anterior descending were related to significantly lower FFR values and to a higher rate of a positive FFR compared with those in distal left anterior descending, left circumflex, and right coronary arteries (0.80±0.09 versus 0.84±0.08 versus 0.88±0.09 versus 0.91±0.04; P<0.0001). The presence of a collateralized chronic total occlusion was associated with significantly lower FFR values (0.80±0.07 versus 0.85±0.09; P<0.005). At multivariate analysis MJI, minimal lumen diameter, and presence of a collateralized chronic total occlusion were confirmed as significant predictors of FFR. CONCLUSIONS: A larger amount of perfused myocardium subtended by a stenosis is associated with a higher probability that an angiographically intermediate coronary stenosis is functionally significant.

Sodium bicarbonate plus N-acetylcysteine to prevent contrast-induced nephropathy in primary and rescue percutaneous coronary interventions: the BINARIO (BIcarbonato e N-Acetil-cisteina nell'infaRto mIocardico acutO) study.

AIMS: Contrast-induced nephropathy (CIN) is a frequent and potentially harmful complication of percutaneous coronary interventions (PCI), especially in the setting of ST-elevation myocardial infarction (STEMI). We tested the efficacy of a sodium bicarbonate (SB)-based hydration in urgent PCI for STEMI. METHODS AND RESULTS: From June 2009 to September 2010, 262 consecutive STEMI patients undergoing urgent PCI were prospectively enrolled and treated by SB-based hydration (154 mEq/L at 3 ml Kg-1 for one hour followed by 1 ml Kg-1 for six hours) (group A). As controls, 262 consecutive STEMI patients receiving 0.9% saline hydration (1 ml Kg-1 for 24 hours) before June 2009 were retrospectively enrolled (group B). Both groups received high-dose N-acetylcysteine (NAC). The primary endpoint was the composite of in-hospital death, need for dialysis and CIN (≥25% increase in serum creatinine at 48 hours). The two groups were comparable for baseline clinical and procedural characteristics, for Mehran risk score and baseline estimated glomerular filtration rate. The primary combined endpoint was significantly reduced in group A as compared to group B (9.2 vs. 18.7%, p=0.023) with a number needed to treat (NNT) of 11. Specifically, a significant reduction of both in-hospital death (2.3 vs. 6.1%, p=0.049, NNT 27) and CIN (8.0 vs. 14.1%, p=0.03, NNT 17) was observed, with no difference in the need for dialysis. CONCLUSIONS: Our data indicate that hydration with sodium bicarbonate in addition to high-dose NAC in the setting of urgent PCI for STEMI is associated with a net clinical benefit.

Maximal hyperemia in the assessment of fractional flow reserve: intracoronary adenosine versus intracoronary sodium nitroprusside versus intravenous adenosine: the NASCI (Nitroprussiato versus Adenosina nelle Stenosi Coronariche Intermedie) study.

OBJECTIVES: This study sought to compare increasing doses of intracoronary (i.c.) adenosine or i.c. sodium nitroprusside versus intravenous (i.v.) adenosine for fractional flow reserve (FFR) assessment. BACKGROUND: Maximal hyperemia is the critical prerequisite for FFR assessment. Despite i.v. adenosine currently representing the recommended approach, i.c. administration of adenosine or other coronary vasodilators constitutes a valuable alternative in everyday practice. However, it is surprisingly unclear which i.c. strategy allows the achievement of FFR values comparable to i.v. adenosine. METHODS: Fifty intermediate coronary stenoses (n = 45) undergoing FFR measurement were prospectively and consecutively enrolled. Hyperemia was sequentially induced by incremental boli of i.c. adenosine (ADN) (60 µg ADN60, 300 µg ADN300, 600 µg ADN600), by i.c. sodium nitroprusside (NTP) (0.6 µg/kg bolus) and by i.v. adenosine infusion (IVADN) (140 µg/kg/min). FFR values, symptoms, and development of atrioventricular block were recorded. RESULTS: Incremental doses of i.c. adenosine and NTP were well tolerated and associated with fewer symptoms than IVADN. Intracoronary adenosine doses (0.881 ± 0.067, 0.871 ± 0.068, and 0.868 ± 0.070 with ADN60, ADN300, and ADN600, respectively) and NTP (0.892 ± 0.072) induced a significant decrease of FFR compared with baseline levels (p < 0.001). Notably, ADN600 only was associated with FFR values similar to IVADN (0.867 ± 0.072, p = 0.28). Among the 10 patients with FFR values ≤0.80 with IVADN, 5 were correctly identified also by ADN60, 6 by ADN300, 7 by ADN600, and 6 by NTP. CONCLUSIONS: Intracoronary adenosine, at doses higher than currently suggested, allows obtaining FFR values similar to i.v. adenosine. Intravenous adenosine, which remains the gold standard, might thus be reserved for those lesions with equivocal FFR values after high (up to 600 µg) i.c. adenosine doses.

Multiple vertebral fractures precipitate a platypnea-orthodeoxia syndrome in a patient with atrial septal defect and aortic root dilatation: When the upright position becomes intolerable.

Platypnea-orthodeoxia syndrome is a rare disease characterized by dyspnea and oxygen desaturation induced by the upright position and relieved by recumbency. We report a case of a 65-year-old woman with a recent history of traumatic hip and multiple vertebral fractures referred to our institute due to onset of severe acute dyspnea. Transthoracic and transesophageal echocardiography, conducted by intravenous administration of agitated saline contrast solution, revealed the presence of atrial septal defect (ASD) associated with an important bidirectional shunting that was right-to-left directed when the patient was in a sitting position. Surgical closure of ASD resulted in resolution of the syndrome.

The HEART study: a real-world experience using the CID Chrono Carbostent in primary and rescue PCI.

BACKGROUND: Chrono Carbostent (CID, Saluggia, Italy) is characterized by a peculiar coating with Carbofilm which could reduce the risk of thrombosis as compared to other bare metal stents (BMS). This feature should be particularly useful in the setting of primary or rescue percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We tested the efficacy and safety of this stent in patients with STEMI undergoing primary or rescue PCI. Inclusion criteria included the diagnosis of STEMI, a coronary anatomy suitable for stenting and no contraindications to dual antiplatelet therapy for at least 1 month. The primary endpoint was the composite of the following major adverse cardiac events (MACEs) at 12 months: death, recurrence of myocardial infarction and target vessel revascularization. RESULTS: One hundred and seven STEMI patients treated with Chrono Carbostent implantation were enrolled. Eighty-three (77%) patients underwent primary and 24 (23%) rescue PCI. A total of 148 stents were successfully implanted. Cardiogenic shock was present in 12 (11%) patients and in-hospital mortality was 6.5%. Cumulatively, the rate of MACEs at 12 months was 17.7% (deaths 7.4%, target lesion revascularization 9.3%). CONCLUSIONS: In unselected patients with STEMI treated by urgent PCI, the Chrono Carbostent showed a low rate of events in those patients surviving the acute phase of myocardial infarction. Unfortunately, and especially for patients in cardiogenic shock, survival continued to be relatively independent of interventional treatment, even when successfully completed, thus strictly linking prognosis of STEMI to severity of clinical presentation.

Safety and efficacy of G-CSF in patients with ischemic heart failure: the CORNER (Cell Option For Recovery in the Non-Eligible Patients for Revascularization) study.

BACKGROUND: Demonstration that the heart is not a post-mitotic organ has led to clinical trials trying to obtain myocardial repair even in patients with heart failure. AIM OF THE STUDY: To evaluate as a less invasive method for promoting cardiac repair. METHODS: Thirteen patients with ischemic heart failure in NYHA and/or CCS classes ≥ 3 unsuitable for revascularization received G-CSF, as a compassionate use, in addition to optimal medical therapy. Symptoms and cardiac perfusion by gated-SPECT were assessed at baseline and at 4 month follow up. RESULTS: G-CSF was generally well tolerated. NYHA and CCS classes improved significantly from 3 (IR 2.5-3) to 2 (IR 1-2.5) (p = 0.012) and from 3 (IR 1-3) to 1 (IR 1-2) (p = 0.033). Heart failure severity symptoms according to the Minnesota Living with Heart Failure Questionnaire scores exhibited a non significant improvement from 52 ± 27 to 39 ± 26 (p = 0.15). At the Seattle Angina Questionnaire scores (ranging from 0 to 100, higher scores indicating better status), physical limitation improved from 39 ± 31 to 64 ± 29 (p = 0.03), angina stability from 42 ± 29 to 64 ± 28 (p = 0.05), angina frequency from 53 ± 33 to 73 ± 26 (p = 0.04), treatment satisfaction from 67 ± 29 to 83 ± 21 (p = 0.07), disease perception from 37 ± 29 to 66 ± 26 (p = 0.007). Quality of life assessed by a Visual Analogue Scale improved from 33 ± 24 to 64 ± 20 mm (p = 0.003). Stress and differential regional perfusion scores improved significantly from 1.78 ± 1.38 to 1.66 ± 1.38 (p = 0.05) and from 0.35 ± 0.68 to 0.23 ± 0.53 (p = 0.02) respectively. CONCLUSIONS: In patients with ischemic heart failure unsuitable for revascularization, G-CSF is associated to a significant improvement of symptoms, possibly reducing stress-induced ischemia.

Reversible coronary microvascular dysfunction: a common pathogenetic mechanism in Apical Ballooning or Tako-Tsubo Syndrome.

AIMS: To study coronary microvascular dysfunction as possible pathogenetic mechanism in Apical Ballooning Syndrome (ABS). METHODS AND RESULTS: Fifteen ABS patients (all women, 68 +/- 14 years) underwent myocardial contrast echocardiography at baseline during adenosine infusion (140 microg/kg/min) and at 1-month follow-up and compared with a group of anterior ST-elevation myocardial infarction (STEMI) patients with similar clinical characteristics. Myocardial perfusion was assessed by contrast score index (CSI) and endocardial length of contrast defect (contrast defect length, CDL), whereas myocardial dysfunction by wall motion score index (WMSI), endocardial length of contractile dysfunction (wall motion defect length, WMDL), and LV ejection fraction (LVEF). At baseline, no difference in myocardial perfusion and dysfunction were present between the two groups. During adenosine challenge, while no changes were observed in STEMI group, in ABS patients CSI, CDL, WMSI, and WMDL significantly decreased compared with baseline (P < 0.001 vs. baseline for all parameters) and LVEF significantly increased (P = 0.01 vs. baseline). At 1-month follow-up, myocardial perfusion and dysfunction completely recovered in ABS patients (P < 0.001 vs. baseline for all parameters), whereas no significant changes were observed in STEMI group. CONCLUSION: Our data strongly suggest that in ABS, irrespectively of its underlying aetiology, acute and reversible coronary microvascular vasoconstriction could represent a common pathophysiological mechanism.

From bone marrow to the arterial wall: the ongoing tale of endothelial progenitor cells.

Several physiological and pathophysiological stimuli or drugs modulate endothelial progenitor cell (EPC) mobilization. Moreover, levels of circulating EPCs predict cardiovascular risk and left ventricular remodelling after myocardial infarction. Nevertheless, our understanding in this field is complicated by lack of an unequivocal definition of EPCs, thus limiting their clinical applications. This review summarizes current knowledge and uncertainties on EPC characterization and mobilization in the attempt to define their role in the management of cardiovascular diseases.

Feasibility and long-term safety of elective Impella-assisted high-risk percutaneous coronary intervention: a pilot two-centre study.

OBJECTIVE: We evaluated the acute and long-term results of the use of a new intracardiac microaxial pump, the Impella Recover LP 2.5, during elective high-risk percutaneous coronary interventions in a two-centre registry. METHODS: Ten consecutive patients with poor left ventricular function and multivessel or left main coronary artery disease were considered at high risk of haemodynamic compromise and underwent percutaneous coronary interventions with preintervention Impella implantation. Procedural complications, 30-day and 12-month clinical outcome were recorded. Left ventricular ejection fraction was assessed by echocardiography before procedure and after at least 6 months. RESULTS: The Impella was implanted before percutaneous coronary interventions by femoral approach and percutaneous coronary interventions were successfully performed (by contra lateral femoral or radial approach) in all cases. After percutaneous coronary intervention, Impella was removed in all patients, and haemostasis was obtained by prolonged manual compression or by double suture device preimplantation technique. No access-site complication was observed and no patient required transfusions. One patient died after Impella removal due to acute stent thrombosis. The other patients had an uncomplicated in-hospital course and were discharged within 5 days. At 1-year follow-up, no patient died nor suffered acute myocardial infarction, whereas two patients underwent re-percutaneous coronary intervention. Left ventricular ejection fraction at follow-up increased significantly in this study population (from 31 +/- 7% to 41% +/- 13%, P = 0.02). CONCLUSION: Our results support the feasibility and safety of Impella-assisted percutaneous coronary intervention in high-risk patients. Prospective randomized trials are needed to test the clinical impact of such an innovative approach.

Effect of intensive vs standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: Statins for regeneration after acute myocardial infarction and PCI (STRAP) trial.

BACKGROUND: Intensive statin therapy can lower the risk of recurrence of major cardiac events in patients with acute coronary syndromes. This could be related to the ability of statins to increase levels of Endothelial Progenitor Cells (EPCs), which were demonstrated to be favorably associated with a better prognosis and post-infarction left ventricular remodeling in patients with ischemic heart disease. AIM OF THE STUDY: First, to evaluate, in a randomized clinical trial, the effect of an intensive vs a standard treatment with statins on EPC mobilization in patients undergoing a successful primary or rescue percutaneous coronary intervention; secondary, to evaluate whether left ventricular remodeling could be influenced by statin therapy through EPC mobilization. METHODS: Forty ST-segment elevation myocardial infarction (STEMI) patients undergoing a successful primary or rescue PCI were randomized to receive atorvastatin 80 mg immediately after the admission (Intensive Treatment, IT) or atorvastatin 20 mg from the day of the discharge (Standard Treatment, ST). CD34+/KDR+ EPC count by flow cytometry and left ventricular function by 2-D Echo were measured on admission, at discharge and at 4 months follow up. RESULTS: We found that EPC count was similar in the two groups of patients both on admission and at discharge. At follow up, however, EPC count was higher in patients randomized to IT compared to patients randomized to ST (7.59+/-7.30 vs 3.04+/-3.93, p=0.04). However, LV volumes, ejection fraction and wall motion score index were similar in both groups. CONCLUSIONS: An intensive statin treatment after primary or rescue PCI is associated with a higher EPC count at follow up as compared to standard treatment. This beneficial effect did not translate in an improvement of LV function.