Andrea D’Ambrosio

Randomized Trial of Atorvastatin for Reduction of Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery Results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) Study

Background— Atrial fibrillation (AF) after cardiac surgery is associated with increased risk of complications, length of stay, and cost of care. Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF. We tested this observation in a randomized, controlled trial. Methods and Results— Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass, without previous statin treatment or history of AF, were enrolled. Patients were randomized to atorvastatin (40 mg/d, n=101) or placebo (n=99) starting 7 days before operation. The primary end point was incidence of postoperative AF; secondary end points were length of stay, 30-day major adverse cardiac and cerebrovascular events, and postoperative C-reactive protein (CRP) variations. Atorvastatin significantly reduced the incidence of AF versus placebo (35% versus 57%, P=0.003). Accordingly, length of stay was longer in the placebo versus atorvastatin arm (6.9±1.4 versus 6.3±1.2 days, P=0.001). Peak CRP levels were lower in patients without AF (P=0.01), irrespective of randomization assignment. Multivariable analysis showed that atorvastatin treatment conferred a 61% reduction in risk of AF (odds ratio 0.39, 95% confidence interval 0.18 to 0.85, P=0.017), whereas high postoperative CRP levels were associated with increased risk (odds ratio 2.0, 95% confidence interval 1.2 to 7.0, P=0.01). The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms. Conclusions— Treatment with atorvastatin 40 mg/d, initiated 7 days before surgery, significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay. These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery.

Impaired Flow-Mediated Dilation and Risk of Restenosis in Patients Undergoing Coronary Stent Implantation

Background—Impaired endothelial function is a key event in the atherosclerosis process and predicts future cardiovascular events in subjects with and without coronary artery disease (CAD). We performed the first prospective study evaluating whether early measurement of brachial artery endothelium-dependent dilation (flow-mediated dilation [FMD]) after coronary stenting could predict occurrence of in-stent-restenosis. Methods and Results—The study population included 136 patients with single-vessel CAD undergoing percutaneous coronary intervention (PCI) with stenting and at least 6 months of follow-up. All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI; FMD was investigated before and after 5 minutes of occlusion of the brachial artery, and nitroglycerin-mediated dilation was investigated before and after administration of sublingual nitrates. Clinical in-stent restenosis was demonstrated in 20 patients (15%), whereas 116 patients (85%) remained free of signs or symptoms of recurrent ischemia. FMD was significantly impaired in patients with restenosis versus those without restenosis (percent diameter variation 4.6±5.8% versus 9.5±6.6%, P=0.002); moreover, 4% of patients with FMD ≥7% (median value) developed in-stent restenosis versus 28% of those with FMD <7% (P=0.0001). On multivariate analysis, FMD was the strongest predictor of restenosis (OR 4.5, 95% CI 2.4 to 12.0); conversely, nitroglycerin-mediated dilation did not independently predict the risk of restenosis (OR 2.4, 95% CI 0.8 to 6.3). Conclusions—This is the first prospective study indicating that impaired FMD independently predicts occurrence of in-stent restenosis in patients undergoing PCI. Early evaluation of endothelial function after stenting may represent a useful screening tool to stratify patients according to future risk of restenosis.

Usefulness of Statin Pretreatment to Prevent Contrast-Induced Nephropathy and to Improve Long-Term Outcome in Patients Undergoing Percutaneous Coronary Intervention

Contrast-induced nephropathy (CIN) is an important cause of mortality and morbidity in patients undergoing angiography. This study investigated whether statins decrease incidence of CIN in the setting of percutaneous coronary intervention (PCI) and evaluated the influence of such potential benefit on long-term outcome. Four-hundred thirty-four patients undergoing PCI were prospectively enrolled and followed up to 4 years. Patients were stratified according to preprocedural statin therapy (260 statin treated, 174 statin naive). CIN was defined as a postprocedural increase in serum creatinine of >or=0.5 mg/dl or>25% from baseline. Follow-up assessment included 4-year occurrence of major adverse cardiac events. Statin-treated patients had a significantly lower incidence of CIN (3% vs 27%, p<0.0001; 90% risk decrease) and had better postprocedural creatinine clearance (80+/-20 vs 65+/-16 ml/min, p<0.0001). Benefit of statin before treatment was observed in all subgroups, except in patients with a pre-existing creatinine clearance<40 ml/min. During follow-up, CIN was a predictor of poorer outcome; 4-year survival free of major adverse cardiac events was highest in statin-treated patients without CIN (95%, p<or=0.015) and lowest in statin-naive patients with CIN (53%, p<or=0.018). In conclusion, patients receiving statins before PCI have a significant decrease of CIN; this early protective effect translates into better long-term event-free survival. These results may lend further support to utilization of statins as adjuvant pharmacologic therapy before PCI.

Simvastatin attenuates leucocyte–endothelial interactions after coronary revascularisation with cardiopulmonary bypass

Objective: To investigate the effects of preoperative simvastatin treatment on leucocyte–endothelial interactions following coronary artery bypass surgery with cardiopulmonary bypass. Design: Double blind crossover study. Experiments on polymorphonuclear cells (neutrophils) were done at the end of cardiopulmonary bypass and one hour postoperatively. Endothelial P-selectin expression and neutrophil/endothelial adhesion were evaluated under either normoxic or hypoxic conditions. Setting: University hospital (tertiary referral centre). Patients: Three groups of patients undergoing coronary bypass surgery: 20 patients taking simvastatin for cholesterol control, 16 patients not responsive to simvastatin, and 20 controls. Main outcome measures: Expression of neutrophil CD11b and endothelial P-selectin; adhesion of neutrophils to endothelium. Results: Cardiopulmonary bypass resulted in a significant increase in neutrophil CD11b expression in all groups. Similarly, the exposure of saphenous vein to hypoxia/reoxygenation induced an augmentation of endothelial P-selectin. However, both neutrophil CD11b expression and endothelial P-selectin exocytosis were less in the simvastatin groups than in the controls. Cardiopulmonary bypass and controlled hypoxia/reoxygenation stimulated neutrophil/endothelial adhesion, but the number of adhering cells was less in the simvastatin groups than in the controls, irrespective of the cholesterol concentration. Treatment of endothelial cells with L-NAME completely reversed the effects of simvastatin. Conclusions: Pretreatment with simvastatin reduces neutrophil adhesion to the venous endothelium in patients undergoing coronary surgery, irrespective of its efficacy at lowering cholesterol concentration.

Prognostic value of interleukin-1 receptor antagonist in patients undergoing percutaneous coronary intervention.

Elevated plasma levels of inflammatory markers, such as C-reactive protein (CRP), have been associated with adverse outcome in selected patients with coronary artery disease (CAD) treated with coronary angioplasty or stenting. The aim of this study was to evaluate the predictive value of preprocedural interleukin-1 receptor antagonist (IL-1Ra) plasma levels for long-term major adverse cardiac events (MACE) in a series of unselected patients with symptomatic CAD treated with percutaneous coronary intervention (PCI). Seventy-three consecutive patients (62 men, aged 62 +/- 9 years) undergoing PCI were enrolled in a prospective follow-up study. IL-1Ra and CRP plasma levels were measured before the procedure; 36 patients (49%) had unstable angina pectoris on admission, 37 (51%) had chronic stable angina pectoris, and 30 (41%) had multivessel CAD, 15 of whom underwent multivessel PCI. Success was achieved in all 73 patients, with coronary stenting performed in 63 (86%). Follow-up clinical assessment included occurrence of MACE at 3, 6, 12, and 18 months. Logistic regression analysis, performed to determine independent predictors of MACE, identified IL-1Ra levels in the upper quartile as the only independent predictive factor of MACE at 18 months (19% in the fourth quartile vs 0% in the first quartile; p = 0.032). Patients with high preprocedural CRP levels (fourth quartile) had a nonsignificant increased risk of MACE (p = 0.09). Thus, preprocedural IL-1Ra plasma levels appear to be a valuable independent predictive factor of MACE in unselected patients undergoing PCI.

Pressure distension stimulates the expression of endothelial adhesion molecules in the human saphenous vein graft

BACKGROUND Mechanical trauma occurring during saphenous vein graft harvesting plays a major role in graft failure after coronary bypass surgery. There is increasing evidence that neutrophil-endothelial interaction is involved in the pathogenesis of early graft occlusion. This study evaluates the effect of pressure distension on the expression of endothelial adhesion molecules in human saphenous vein. METHODS Segments of saphenous vein graft (SVG) were collected from 20 patients undergoing coronary bypass surgery. We evaluated the expression of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and P-selectin on SVG endothelium under basal conditions and after pressure distension at 300 mm Hg. In the same experimental setting we also evaluated adhesion of both unstimulated and activated neutrophils to the endothelium of SVG. RESULTS Control endothelial cells exhibited only a weak staining for intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and P-selectin, whereas the levels of adhesion molecules increased significantly in the distended veins. Similarly, significantly greater adhesion of both unstimulated and activated neutrophils was observed in distended veins compared with control veins. CONCLUSIONS Pressure distension of SVG before coronary bypass surgery induces upregulation of endothelial adhesion molecules, with subsequent increase in neutrophil adhesion to the endothelium. Neutrophil adhesion to endothelial cells may contribute to early failure of SVG.

Early and long-term results of stenting of diffuse coronary artery disease

Diffuse coronary artery disease (CAD) is considered unfavorable for interventional procedures; however, the results of stenting of diffuse CAD have not been completely characterized. We performed stenting in 100 consecutive patients with diffuse CAD, defined as significant stenosis >20 mm (n = 59 patients), multiple significant stenoses in the same artery (n = 23 patients), or significant narrowing involving the whole length of the coronary artery (n = 18 patients). Angiographic success was achieved in 103 arteries (100%) and clinical success was obtained in all 100 patients. There were no deaths; no patient had stent closure, acute myocardial infarction, or required emergency coronary artery bypass surgery. All 100 patients had >6 months follow-up (mean 18 +/- 7 months, range 7 to 31); 77 (77%) remained asymptomatic, and 5 (5%) had acute myocardial infarction, of whom 2 died (2%). In-stent restenosis was observed in 12 patients (12%) and repeat angioplasty was performed in 10. Including those patients who underwent repeat angioplasty, 89 (89%) maintained clinical improvement and 95 (95%) were alive and free of bypass surgery during follow-up. Life-table analysis showed 86% freedom from death, myocardial infarction, and target lesion revascularization at 28 months. Thus, selected patients with diffuse CAD may be treated with satisfactory acute and long-term results by stent implantation.

Response to Letters Regarding Article, “Randomized Trial of Atorvastatin for Reduction of Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery: Results of the ARMYDA-3 (Atorvastatin for Reduction of Myocardial Dysrhythmia After Cardiac Surgery) Study”

We thank Drs Padfield and Shroff for their interest in our paper.1 Although randomization is the best way to obtain homogenous groups of patients, this cannot produce identical characteristics, and the possibility of finding differences increases with the number of parameters included in the analysis. In the ARMYDA-3 trial, we assessed a total of 34 demographic/clinical features and 18 perioperative features …

Percutaneous closure of patent foramen ovale in a patient with situs viscerum inversus.

We describe the case of a patient with situs viscerum inversus totalis in whom we performed percutaneous closure of a patent foramen ovale. This case report may represent a further contribution to illustrate instrumental and interventional issues to consider in patients with situs viscerum inversus; it is also an example in which a background in embryology and congenital heart disease may aid cardiologists for the well-tolerated and effective diagnosis and treatment of adult patients with cardiac anomalies.