Marcello Ravani

Plasma N-e-(carboxymethyl)lysine levels are associated with the extent of vessel injury after coronary arterial stenting

ObjectiveIn animal models, increased tissue receptor for advanced glycation end products and its ligands, including N-ϵ-(carboxymethyl)lysine (CML), are critically implicated in postprocedural intimal hyperplasia after balloon injury. In patients undergoing percutaneous coronary interventions with stenting, we investigated whether plasma levels of CML and the soluble form of receptor for advanced glycation end products (sRAGE) changed during poststenting follow-up. MethodsWe studied 81 patients with coronary artery disease who underwent successful percutaneous coronary interventions. Plasma levels of CML and sRAGE were measured before intervention, and at 1 day and 180 days of follow-up. ResultsCML levels increased significantly at day 1 after stenting and persisted at an elevated level at 180 days (P=0.013), whereas sRAGE levels increased significantly at 180 days (P=0.011). CML levels were significantly higher in multivessel-treated patients than in single-vessel-treated patients both at 1 day and 180 days of follow-up. In addition, CML values were positively associated with the extent of stent area at 1 day and 180 days of follow-up (r=0.278, P=0.022 and r=0.315, P=0.012, respectively). In logistic regression analysis, only the extent of stent area predicted adverse clinical events at 180-day follow-up (P=0.03, odds ratio=14.25, confidence interval=1.25–162.2). ConclusionThis study supports the hypothesis that increased circulating levels of CML occurred in the presence of vascular injury. This persistent rise of CML could amplify an inflammatory phenomenon triggered by stent placement and thus contributes to coronary artery disease progression.

Left atrial appendage occlusion in high-risk patients with non-valvular atrial fibrillation

Objective Percutaneous left atrial appendage (LAA) occlusion has been developed as a viable option for stroke and thromboembolism prevention in patients with non-valvular atrial fibrillation (NVAF) and at high risk for cerebral cardioembolic events. Data on device implantation and long-term follow-up from large cohorts are limited. Methods 110 consecutive patients with NVAF and contraindications to oral anticoagulants (OACs) underwent LAA occlusion procedures and achieved a longer than 1 year follow-up. All patients were enrolled in a prospective registry. Procedures were performed using the Amplatzer Cardiac Plug or Amulet guided by fluoroscopy and intracardiac echocardiography. Results Mean age of the population was 77±6 years old; 68 were men. Atrial fibrillation was paroxysmal in 20%, persistent in 15.5% and permanent in 64.5% of cases, respectively. Mean CHA2DS2-VASc and HAS-BLED scores were 4.3±1.3 and 3.4±1, respectively. Technical success (successful deployment and implantation of device) was achieved in 100% of procedures. Procedural success (technical success without major procedure-related complications) was achieved in 96.4%, with a 3.6% rate of major procedural complications (three cases of pericardial tamponade requiring drainage and one case of major bleeding). Mean follow-up was 30±12 months (264 patient-years). Annual rates for ischaemic stroke and for other thromboembolic events were respectively 2.2% and 0%, and annual rate for major bleeding was 1.1%. Conclusions Our data suggest LAA occlusion in high-risk patients with NVAF not suitable for OACs is feasible and associated with low complication rates as well as low rates of stroke and major bleeding at long-term follow-up.

Osteopontin plasma levels and accelerated atherosclerosis in patients with CAD undergoing PCI: a prospective clinical study.

ObjectivesGrowing evidence supports the role played by inflammation in atherosclerosis. Identifying sensitive biomarkers is useful in predicting accelerated atherosclerosis. We investigated prospectively the relationship between plasma levels of inflammatory biomarkers [osteopontin, C-reactive protein (CRP), interleukin-6 (IL-6)] and instent restenosis, and rapid coronary plaque progression in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). MethodsWe studied 77 patients with CAD: 45 affected by unstable angina/non-ST elevation myocardial infarction [acute coronary syndrome (ACS)], and 32 by chronic coronary syndrome (CCS). Plasma osteopontin, IL-6, and CRP levels were measured before intervention in all patients; measurements were carried out on the basis of the following time course at 1,15, 30, 90, and 180 days follow-up in a subgroup of 39 consenting patients. Clinical and biohumoral data were correlated with baseline and 6-month PCI follow-up angiography. ResultsOsteopontin, IL-6, and CRP were higher in patients with ACS than in those with CCS (analysis of variance: P<0.001, 0.05, and 0.05, respectively). Baseline osteopontin levels proved to be associated with rapid coronary plaque progression (P=0.005) and instent restenosis (P=0.05). The highest osteopontin levels were found in patients with CAD with both rapid plaque progression and instent restenosis (P=0.003). PCI increased inflammatory markers acutely, and osteopontin remained elevated in patients with ACS. Patients with ACS showed a higher percentage (74%) of rapid plaque progression than those with CCS (26%) (P<0.05). ConclusionThe study prospectively shows the link between inflammatory status and accelerated atherosclerosis in patients with CAD undergoing PCI. The baseline and persistent rise of osteopontin is an expression of its contribution to the accelerated plaque progression, and therefore osteopontin may be a useful prognostic biomarker.

Acute hemodynamic effects of endogenous adenosine in patients with chronic heart failure.

OBJECTIVE The objective of this study was to assess the acute hemodynamic effects of endogenous adenosine accumulation in patients with chronic heart failure. Exogenously administered adenosine has been shown to reduce pulmonary vascular resistance and to increase cardiac index in normal subjects and in patients with pulmonary hypertension or end-stage biventricular heart failure. Endogenous adenosine accumulation can be provoked by dipyridamole. METHODS AND RESULTS Ultra-low-dose dipyridamole (0.07 mg/kg/min for 4 minutes) was administered in 20 patients with either symptomatic idiopathic (n = 12) or ischemic (n = 8) dilated cardiomyopathy and reduced left ventricular ejection fraction (mean 25%+/-5%). Hemodynamic variables were measured before and within 1 minute from the end of dipyridamole infusion. After dipyridamole administration, a mild but significant increase in heart rate (4.5%; p = 0.03) and reduction in mean blood pressure (6.8%; p < 0.001) without changes in right atrial pressure (p = NS) were detected. Dipyridamole increased cardiac output by 26.6% (p < 0.001), cardiac index by 24% (p < 0.001), and stroke volume by 19.8% (p < 0.001), with concomitant 24.6% reduction of systemic vascular resistance (p < 0.001). Moreover, dipyridamole reduced mean pulmonary artery pressure by 8.3% (p < 0.01) and pulmonary vascular resistance by 33.3% (p = 0.001), without changes in pulmonary wedge pressure (p = NS). A significant correlation between percent decrease from baseline in pulmonary and systemic vascular resistance (r = 0.66; p = 0.002) was found after administration of dipyridamole. CONCLUSIONS Endogenous adenosine accumulation induced by ultra-low-dose dipyridamole infusion acutely improves the hemodynamic profile, decreasing pulmonary and, to a lower extent, systemic vascular resistance and increasing cardiac index in patients with severe chronic heart failure.

Drug Eluting Balloon: A Multipurpose Tool for Coronary Revascularization With Optimal Long‐Term Follow‐Up Results

AIMS This study aimed to evaluate safety and efficacy of drug-coated balloon (DCB) at long-term follow-up; a large series of real-life patients underwent revascularization with DCB for a wide spectrum of clinical and angiographic situations. METHODS AND RESULTS One hundred ten patients underwent percutaneous revascularization using paclitaxel eluting balloon (Sequent Please, Braun, Germany). End-points were major adverse cardiac events (MACE; all-cause death, myocardial infarction [MI], target vessel revascularisation [TVR], and vessel thrombosis). DCB were used for stable angina (58%), unstable angina/nonST elevation MI (31%) and ST elevation MI (11%). DCB were used for in-stent restenosis (61%), small vessel disease (25%), with bare metal stent (BMS) to avoid long dual antiplatelet therapy (10%) or for impossibility to place a stent (4%). Cumulative MACE at follow-up (median 23 months, IQR 13-32) was 12.7%, with 8.2% all-cause death (1 fatal MI), 4.5% TVR, 3.6% TLR, and no vessel thrombosis. Three of four TLRs occurred in patients who received DEB for DES restenosis. CONCLUSIONS DCB are a very effective tool for a variety of clinical and angiographic situations. DCB use seems to be affected by a low rate of complications and adequate results at long-term follow-up.

Self-expanding stent for complex percutaneous coronary interventions: A real life experience

AIM Self-expanding stents represent a re-emerging option for percutaneous coronary interventions. Their application covers a wide spectrum of angiographic situations, i.e., coronary bifurcations, acute coronary syndromes with large thrombotic burden and stenosis of ectatic coronaries. We review our experience with self-expanding stents for different clinical and angiographic indications, with long clinical follow-up. METHODS From 2011 to 2013 we used self-expanding STENTYS® stents in 40 consecutive patients followed-up for death from any cause and from cardiovascular cause, myocardial infarction, target lesion revascularization (TLR), stent thrombosis (mean 21±13months). We also revised rate of procedural outcomes, acute stent thrombosis and TLR in patients treated with conventional stents for similar clinical/angiographic situations, in the same period at our institution. RESULTS We identified three anatomical settings of STENTYS® use: coronary bifurcations with proximal/distal main branch diameter discrepancy (55% of cases), massive thrombotic burden in the setting of acute coronary syndrome (35% of cases) and stenosis of ectatic coronaries (15%). We observed one death related to acute heart failure and 1 case (2.5%) of acute stent thrombosis (2.5% in the control group). During follow-up 2 cases of stent restenosis leading to TLR (5%) occurred (6.25% in the control group). CONCLUSIONS According to our real life experience, self-expanding STENTYS® stents appear to be an effective tool for different angiographic situations in which they may be preferable to balloon-expandable stents, showing a low rate of complications and good results at long term follow-up.

Acute enoximone effect on systemic and renal hemodynamics in patients with heart failure

SummaryPatients with heart failure generally show improvement in their clinical condition after enoximone infusion over the period of treatment; this effect cannot be ascribed only to the known hemodynamic action of this drug. Thirty-six patients (age range 44–82 years) with heart failure (NYHA class II–IV) underwent 48-hour enoximone infusion to study whether this prolonged improvement might depend on changes in systemic or renal hemodynamics or in neurohormonal balance. All patients underwent Swan-Ganz hemodynamic monitoring; renal plasma flow, glomerular filtration rate, plasma atrial natriuretic factor (ANF), and plasma renin activity (PRA) were all measured at baseline, at the peak of the enoximone action, and 48 hours after drug discontinuation. The main hemodynamic parameters were significantly improved during enoximone infusion and after drug discontinuation. The cardiac index basal value of 2.2±0.1 l/min/m2 increased to 3.1±0.1 l/min/m2 after 24-hour therapy (p<0.01); similarly, pulmonary wedge pressure, mean pulmonary arterial pressure, and right atrial pressure decreased markedly (p<0.01). Beneficial effects were also observed in renal hemodynamics; indeed, renal plasma flow (basal value 485±39 ml/min) increased significantly after 24-hour enoximone infusion (575±35 ml/min; p<0.01), and this tendecy was also observed 48 hours after drug discontinuation. No significant modifications were observed in plasma hormone data; however, the PRA plasma level had a tendency to decrease. We conclude that in patients with heart failure, enoximone infusion has a less marked effect on renal hemodynamics, but this is more lasting than systemic hemodynamic effects. The tendency of PRA to decrease (although not statistically significant), still detectable 2 days after treatment in the presence of steady high plasma ANF concentrations, may also contribute to the paradoxical longlasting benefit despite the short-lived improvement in systemic hemodynamles after brief cycles of enoximone infusion.

Development and validation of a risk stratification score for new-onset atrial fibrillation in STEMI patients undergoing primary percutaneous coronary intervention

New‐onset atrial fibrillation (NOAF) is a complication not infrequent in patients with acute ST‐segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) and has been associated with worse in‐hospital and long‐term prognosis. We aimed to develop and validate a risk score based on common clinical risk factors and routine blood biomarkers to assess the early incidence of NOAF post‐pPCI, before discharge.

Influence of involvement of anterior leaflet versus posterior leaflet on residual regurgitation as assessed by transesophageal echocardiography in patients undergoing valve repair for mitral regurgitation due to mitral valve prolapse

BackgroundRepair of anterior leaflet prolapse is technically more challenging and this might influence outcomes as compared to the repair of posterior leaflet prolapse in patients undergoing surgical correction of mitral regurgitation. We investigated the association of anterior leaflet prolapse with minor residual mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) who underwent valve repair.MethodsEligible for this study were consecutive patients with severe MR due to MVP, who underwent mitral valve repair with residual MR by postpump transesophageal echocardiography ≤2+ during a 20-month period at Pasquinucci Hospital, Massa. Patients undergoing other cardiovascular surgical interventions were excluded. Two groups were defined according to the involvement of mitral valve leaflets: group 1, consisting of patients with anterior leaflet prolapse (isolated or not); and group 2, consisting of patients with isolated posterior leaflet prolapse.ResultsA total of 70 patients (18 in group 1 and 52 in group 2) were analyzed. Patients in group 2 were younger than those in group 1, but the difference was not significant (P = 0.052). There were no significant differences between the 2 study groups with respect to other variables. The proportion of patients with residual MR 1+/2+ was higher in group 1 than in group 2 (61.1% vs. 32.7%, respectively; P = 0.034). In a logistic regression model, anterior leaflet prolapse was an independent predictor of residual MR 1+/2+ (odds ratio, 4.0; 95% confidence interval, 1.14 to 14.04; P = 0.03).ConclusionIn our study population, patients with anterior leaflet prolapse had a higher proportion of residual MR 1+/2+ as compared to those with posterior leaflet prolapse after repair of mitral valve.

First-in-Human Percutaneous Left Atrial Appendage Occlusion Procedure Guided by Real-Time 3-Dimensional Intracardiac Echocardiography

Transesophageal echocardiography is the most commonly used imaging modality for percutaneous closure of left atrial appendage limited mainly by the need for general anesthesia. Intracardiac echocardiography (ICE) requires only local anesthesia, but imaging quality may be suboptimal. Real-time 3-