NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs

During cardiopulmonary bypass (CPB), neutrophils become activated due to contact with extracorporeal surfaces and binding of complement fragments C3a and C5a, leading to extravasation and subsequent tissue damage. In this study, the effects of the leumedin NPC 15669 (N [9H - (2,7 dimethylfluorenyl - 9 - methoxy) car bonyl]-L-leucine), a leukocyte recruitment inhibitor, were evaluated in a pig model of CPB. NPC 15669 caused significant inhibition of CPB associated increase in CD18 upregulation, lung tissue myeloperoxidase content, and percentage wet weight compared to controls. Lung histology revealed clear airways and minimal neutrophil infiltration in treated animals vs. significant oedema and cellular infiltration in controls. It is concluded that CPB causes a dramatic increase in neutrophil CD18, and that leumedins are effective in inhibiting neutrophil activation and subsequent tissue injury when administered during CPB

Ablation of atrial fibrillation with the Epicor system: a prospective observational trial to evaluate safety and efficacy and predictors of success

<p>Abstract</p> <p>Background</p> <p>High intensity focused ultrasound (HIFU) energy has evolved as a new surgical tool to treat atrial fibrillation (AF). We evaluated safety and efficacy of AF ablation with HIFU and analyzed predictors of success in a prospective clinical study.</p> <p>Methods</p> <p>From January 2007 to June 2008, 110 patients with AF and concomitant open heart surgery were enrolled into the study. Main underlying heart diseases were aortic valve disease (50%), ischemic heart disease (48%), and mitral valve disease (18%). AF was paroxysmal in 29%, persistent in 31%, and long standing persistent in 40% of patients, lasting for 1 to 240 months (mean 24 months). Mean left atrial diameter was 50 ± 7 mm. Each patient underwent left atrial ablation with the Epicor system prior to open heart surgery. After surgery, the patients were treated with amiodarone and coumadin for 6 months. Follow-up studies including resting ECG, 24 h Holter ECG, and echocardiography were obtained at 6 and 12 months.</p> <p>Results</p> <p>All patients had successful application of the system on the beating heart prior to initiation of extracorporeal circulation. On average, 11 ± 1 ultrasound transducer elements were used to create the box lesion. The hand-held probe for additional linear lesions was employed in 83 cases. No device-related deaths occurred. Postoperative pacemaker insertion was necessary in 4 patients. At 6 months, 62% of patients presented with sinus rhythm. No significant changes were noted at 12 months. Type of AF and a left atrial diameter > 50 mm were predictors for failure of AF ablation.</p> <p>Conclusion</p> <p>AF ablation with the Epicor system as a concomitant procedure during open heart surgery is safe and acceptably effective. Our overall conversion rate was lower than in previously published reports, which may be related to the lower proportion of isolated mitral valve disease in our study population. Left atrial size may be useful to determine patients who are most likely to benefit from the procedure.</p

Concomitant ablation of atrial fibrillation in octogenarians: an observational study

<p>Abstract</p> <p>Background</p> <p>Cardiac surgery is increasingly required in octogenarians. These patients frequently present atrial fibrillation (AF), a significant factor for stroke and premature death. During the last decade, AF ablation has become an effective procedure in cardiac surgery. Because the results of concomitant AF ablation in octogenarians undergoing cardiac surgery are still not clear, we evaluated the outcome in these patients.</p> <p>Methods</p> <p>Among 200 patients undergoing concomitant AF ablation (87% persistent AF), 28 patients were ≥ 80 years (82 ± 2.4 years). The outcome was analysed by prospective follow up after 3, 6, 12 months and annually thereafter. Freedom from AF was calculated according to the Kaplan-Meier method.</p> <p>Results</p> <p>Octogenarians were similar to controls regarding AF duration (48 ± 63.2 versus 63 ± 86.3 months, n.s.) and left atrial diameter (49 ± 6.1 versus 49 ± 8.8 mm, n.s.), but differed in EuroSCORE (17.3 ± 10.93 versus 7.4 ± 7.31%, p < 0.001), prevalence of paroxysmal AF (25.0 versus 11.0%, p = 0.042) and aortic valve disease (67.8 versus 28.5%, p < 0.001). ICU stay (8 ± 16.9 versus 4 ± 7.2 days, p = 0.027), hospital stay (20 ± 23.9 versus 14 ± 30.8 days, p < 0.05), and 30-d-mortality (14.3 versus 4.6%, p = 0.046) were increased. After 12 ± 6.1 months of follow-up (95% complete), 14 octogenarians (82%) and 101 controls (68%, n.s.) were in sinus rhythm; 59% without antiarrhythmic drugs in either group (n.s.). Sinus rhythm restoration was associated with improved NYHA functional class and renormalization of left atrial size. Cumulative freedom from AF demonstrated no difference between groups. Late mortality was higher in octogenarians (16.7 versus 6.1%, p = 0.065).</p> <p>Conclusion</p> <p>Sinus rhythm restoration rate and functional improvement are satisfactory in octogenarians undergoing concomitant AF ablation. Hence, despite an increased perioperative risk, this procedure should be considered even in advanced age.</p

Rest and Dobutamine stress echocardiography in the evaluation of mid-term results of mitral valve repair in Barlow's disease

BACKGROUND: Surgical "anatomical" repair is the most frequent technique used to correct mitral regurgitation due to severe myxomatous valve disease. Debate, however, persists on the efficacy of this technique, as well as on the durability of the repaired valve, and on its functioning and hemodynamics under stress conditions. Thus, a basal and Dobutamine echocardiographic (DSE) study was carried out to evaluate these parameters at mid-term follow-up. METHODS AND RESULTS: Twenty patients selected for the study (12 men and 8 women, mean age 60 ± 9 years) underwent pre- and post-operative transthoracic echocardiography (TTE) and intra-operative transesophageal echocardiography (TEE). At mid-term follow-up (20 ± 5 months) all patients underwent rest TTE and DSE (3 min. dose increments up to 40 microg/Kg/min protocol). Pre-discharge and one-month TTE showed absence of MR in 11 pts., trivial or mild MR in 9 pts. and normal mitral valve area and gradients. Mid-term TTE showed decrease in left atrial and ventricular dimension, in pulmonary artery pressure (sPAP) and grade of MR. During DSE a significant increase in mitral valve area, maximum and mean gradients, sPAP, heart rate and cardiac output and a decrease in systolic annular diameter and left ventricular volume were found; in 6 pts. a transient left ventricular outflow tract obstruction was observed. CONCLUSION: Basal and Dobutamine stress echocardiography proved to be valuable tools for evaluation of mid-term results of mitral valve repair. In our study population, the surgical technique employed had a favourable impact on several cardiac parameters, evaluated by these methods

Postoperative pericardial effusion, pericardiotomy, and atrial fibrillation: an explanatory analysis of the PALACS trial

BackgroundIn the Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery (PALACS) trial, posterior pericardiotomy was associated with a significant reduction in postoperative atrial fibrillation (POAF) after cardiac surgery. We aimed to investigate the mechanisms underlying this effect.MethodsWe included PALACS patients with available echocardiographic data (n = 387/420, 92%). We tested the hypotheses that the reduction in POAF with the intervention was associated with 1) a reduction in postoperative pericardial effusion and/or 2) an effect on left atrial size and function. Spline and multivariable logistic regression analyses were used.ResultsMost patients (n = 307, 79%) had postoperative pericardial effusions (anterior 68%, postero-lateral 51.9%). The incidence of postero-lateral effusion was significantly lower in patients undergoing pericardiotomy (37% vs 67%; P P = .42), but there was a nonsignificant trend towards larger postero-lateral effusion in the POAF group (5.0 [IQR 3.0–9.0] vs 4.0 [IQR 3.0–6.4] mm; P = .06). There was a non-linear association between postero-lateral effusion and POAF at a cut-off at 10 mm (OR 2.70; 95% CI 1.13, 6.47; P = .03) that was confirmed in multivariable analysis (OR 3.5, 95% CI 1.17, 10.58; P = 0.02). Left atrial dimension and function did not change significantly after posterior pericardiotomy.ConclusionsReduction in postero-lateral pericardial effusion is a plausible mechanism for the effect of posterior pericardiotomy in reducing POAF. Measures to reduce postoperative pericardial effusion are a promising approach to prevent POAF.Graphical abstractPathophysiological mechanisms explaining the association between postoperative pericardial effusion and the occurrence of postoperative atrial fibrillation. Hb, hemoglobin; MetHb, methemoglobin; OxyHb, oxyhemoglobin; ROS, reactive oxygen species.Cardiolog

Results of matching valve and root repair to aortic valve and root pathology

ObjectiveFor patients with aortic root pathology and aortic valve regurgitation, aortic valve replacement is problematic because no durable bioprosthesis exists, and mechanical valves require lifetime anticoagulation. This study sought to assess outcomes of combined aortic valve and root repair, including comparison with matched bioprosthesis aortic valve replacement.MethodsFrom November 1990 to January 2005, 366 patients underwent modified David reimplantation (n = 72), root remodeling (n = 72), or valve repair with sinotubular junction tailoring (n = 222). Active follow-up was 99% complete, with a mean of 5.6 ± 4.0 years (maximum 17 years); follow-up for vital status averaged 8.5 ± 3.6 years (maximum 19 years). Propensity-adjusted models were developed for fair comparison of outcomes.ResultsThirty-day and 5-, 10-, and 15-year survivals were 98%, 86%, 74%, and 58%, respectively, similar to that of the US matched population and better than that after bioprosthesis aortic valve replacement. Propensity-score–adjusted survival was similar across procedures (P > .3). Freedom from reoperation at 30 days and 5 and 10 years was 99%, 92%, and 89%, respectively, and was similar across procedures (P > .3) after propensity-score adjustment. Patients with tricuspid aortic valves were more likely to be free of reoperation than those with bicuspid valves at 10 years (93% vs 77%, P = .002), equivalent to bioprosthesis aortic valve replacement and superior after 12 years. Bioprostheses increasingly deteriorated after 7 years, and hazard functions for reoperation crossed at 7 years.ConclusionsValve preservation (rather than replacement) and matching root procedures have excellent early and long-term results, with increasing survival benefit at 7 years and fewer reoperations by 12 years. We recommend this procedure for experienced surgical teams

Relationship between mitral leaflets angles, left ventricular geometry and mitral deformation indices in patients with ischemic mitral regurgitation: imaging by echocardiography and cardiac magnetic resonance

Chronic ischemic mitral regurgitation (IMR) is associated with a markedly worse prognosis after myocardial infarction (MI).The study aimed to evaluate the relationship between anterior and posterior mitral leaflet angle (MLA) values, left ventricle remodeling and severity of ischaemic mitral regurgitation (IMR). Methods: Forty-two patients (age 63.5 ± 9.7 years, 36 men) with chronic IMR (regurgitant volume, RV > 20 ml; >6 months after MI) underwent transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR) imaging. Anterior and posterior MLA, determined by echocardiography, were correlated with indices of LV remodeling, mitral apparatus deformation and IMR severity by CMR. The anterior and posterior MLA was 25.41 ± 4.28 and 38.37 ± 8.89° (mean ± SD). In 5 patients (11.9%) the posterior MLA was ≥45°. There was a significant correlation between anterior MLA and RV (r = 0.74, P = 0.01). For patients with RV > 30 ml this correlation was stronger (r = 0.97, P = 0.005) and, in addition, there was a correlation between the RV and posterior MLA (r = 0.90, P = 0.037), between tenting area and posterior MLA (r = 0.90, P = 0.04), and between tenting area and anterior MLA (r = 0.82, P = 0.08). With regard to LV remodeling parameters, there was weaker but significant correlation between posterior MLA and LV end-diastolic volume index (r = 0.35, P = 0.031), LV end-systolic volume index (r = 0.37, P = 0.021), stroke volume (r = 0.35, P = 0.03), sphericity index (r = 0.33, P = 0.041). Anterior MLA correlated with wall motion score index (r = 0.41, P = 0.019). Besides, there was a correlation between posterior MLA and left atrial volume (r = 0.41, P = 0.012). Measurement of anterior and posterior MLA may play an important role in evaluating patients with IMR

Amaze: a randomized controlled trial of adjunct surgery for atrial fibrillation

OBJECTIVES: Atrial fibrillation (AF) reduces survival and quality of life (QoL). It can be treated at the time of major cardiac surgery using ablation procedures ranging from simple pulmonary vein isolation to a full maze procedure. The aim of this study is to evaluate the impact of adjunct AF surgery as currently performed on sinus rhythm (SR) restoration, survival, QoL and costeffectiveness. METHODS: In a multicentre, Phase III, pragmatic, double-blinded, parallel-armed randomized controlled trial, 352 cardiac surgery patients with >3 months of documented AF were randomized to surgery with or without adjunct maze or similar AF ablation between 2009 and 2014. Primary outcomes were SR restoration at 1 year and quality-adjusted life years at 2 years. Secondary outcomes included SR at 2 years, overall and stroke-free survival, medication, QoL, cost-effectiveness and safety. RESULTS: More ablation patients were in SR at 1 year [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.20–3.54; P = 0.009]. At 2 years, the OR increased to 3.24 (95% CI 1.76–5.96). Quality-adjusted life years were similar at 2 years (ablation - control -0.025, P = 0.6319). Significantly fewer ablation patients were anticoagulated from 6 months postoperatively. Stroke rates were 5.7% (ablation) and 9.1% (control) (P = 0.3083). There was no significant difference in stroke-free survival [hazard ratio (HR) = 0.99, 95% CI 0.64–1.53; P = 0.949] nor in serious adverse events, operative or overall survival, cardioversion, pacemaker implantation, New York Heart Association, EQ-5D-3L and SF-36. The mean additional ablation cost per patient was £3533 (95% CI £1321–£5746). Cost-effectiveness was not demonstrated at 2 years. CONCLUSIONS: Adjunct AF surgery is safe and increases SR restoration and costs but not survival or QoL up to 2 years. A continued follow-up will provide information on these outcomes in the longer term