Lars Willy Andersen

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Valve Stenosis 1-Year Results From the All-Comers NOTION Randomized Clinical Trial

BACKGROUND Transcatheter aortic valve replacement (TAVR) is an option in certain high-risk surgical patients with severe aortic valve stenosis. It is unknown whether TAVR can be safely introduced to lower-risk patients. OBJECTIVES The NOTION (Nordic Aortic Valve Intervention Trial) randomized clinical trial compared TAVR with surgical aortic valve replacement (SAVR) in an all-comers patient cohort. METHODS Patients ≥ 70 years old with severe aortic valve stenosis and no significant coronary artery disease were randomized 1:1 to TAVR using a self-expanding bioprosthesis versus SAVR. The primary outcome was the composite rate of death from any cause, stroke, or myocardial infarction (MI) at 1 year. RESULTS A total of 280 patients were randomized at 3 Nordic centers. Mean age was 79.1 years, and 81.8% were considered low-risk patients. In the intention-to-treat population, no significant difference in the primary endpoint was found (13.1% vs. 16.3%; p = 0.43 for superiority). The result did not change in the as-treated population. No difference in the rate of cardiovascular death or prosthesis reintervention was found. Compared with SAVR-treated patients, TAVR-treated patients had more conduction abnormalities requiring pacemaker implantation, larger improvement in effective orifice area, more total aortic valve regurgitation, and higher New York Heart Association functional class at 1 year. SAVR-treated patients had more major or life-threatening bleeding, cardiogenic shock, acute kidney injury (stage II or III), and new-onset or worsening atrial fibrillation at 30 days than did TAVR-treated patients. CONCLUSIONS In the NOTION trial, no significant difference between TAVR and SAVR was found for the composite rate of death from any cause, stroke, or MI after 1 year. (Nordic Aortic Valve Intervention Trial [NOTION]; NCT01057173).

Three-year follow-up in a subset of high-risk patients randomly assigned to off-pump versus on-pump coronary artery bypass surgery: the Best Bypass Surgery Trial

Objective To evaluate off-pump versus on-pump coronary artery bypass grafting (CABG) in patients with three-vessel disease and a high-risk operative profile. Design A randomised clinical trial. Setting Rigshospitalet, University Hospital, Copenhagen, Denmark. Participants 341 patients with three-vessel disease and a EuroSCORE of 5 or greater. Main exclusion criteria were previous heart surgery, poor left ventricular function (ejection fraction <30%), or unstable preoperative condition. Intervention CABG performed with versus without cardiopulmonary bypass. Main outcome measure The primary outcome was a composite of major adverse cardiac and cerebrovascular events (MACCE) including all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke and coronary reintervention. Results MACCE occurred in 69 (40%) patients allocated to off-pump versus 54 (33%) patients allocated to on-pump CABG during the median 3.7 years of follow-up (HR 1.22; 95% CI 0.86 to 1.75; p=0.26). All-cause mortality was significantly increased in the off-pump group (24% vs 15%; HR 1.66, 95% CI 1.02 to 2.73; p=0.04), but cardiac-related death was not significantly different (10% vs 7%; HR 1.30, 95% CI 0.64 to 2.66; p=0.47). An insignificant trend towards a reduction in myocardial infarction after off-pump CABG was observed (7% vs 14%; HR 0.53, 95% CI: 0.27 to 1.04; p=0.06). Conclusions No significant difference in the primary outcome of MACCE was found between off-pump and on-pump CABG. However, mortality seemed higher after off-pump CABG. Trial registration http://clinicaltrials.gov/ number, NCT00120991.

Acute fatal pulmonary vein occlusion after catheter ablation of atrial fibrillation

AbstractBackground: In treatment of atrial fibrillation (AF) catheter radiofrequency isolation of the pulmonary veins (PVs) has proved to be highly successful. There have been several case reports regarding PV stenosis, however none of these have reported a fatal outcome. Methods and Results: A 31-year-old man was referred to us for treatment of complications related to catheter ablation. According to the documentation from the hospital, the patient underwent segmental ostial PV isolation for treatment of AF. A few hours after the procedure, the patient developed dyspnoea, hemoptysis, and a high fever. The patient was first diagnosed as having pneumonia but five days later transesophageal echocardiography and pulmonal angiography revealed total occlusion of the left superior and inferior PVs. When we received the patient he underwent open-heart surgery, which showed thrombi in the orifices of the left sided PVs protruding into the left atrium. In each of the left sided PVs severe stenosis was seen in the bifurcation area. Thrombus material was removed followed by placement of two stents in each of the left sided pulmonary veins at the first bifurcations. However, the patient died 14 days after the ablation procedure. Selective autopsy of the left lung revealed diffuse alveolar damage, disseminated intravascular coagulation, multiple thrombi formation, and haemorrhagic infarctions. Conclusions: PV stenosis may occur very early after the ablation procedure. Delayed diagnosis can be fatal. The early stenosis may result in thrombus formation in the left atrium and PVs and in this case surgery should be considered.

Cell saver for on-pump coronary operations reduces systemic inflammatory markers: a randomized trial.

BACKGROUND This study investigated whether intraoperative use of a cell saver reduces the systemic inflammatory response after coronary operations using cardiopulmonary bypass (CPB). METHODS The study randomized 29 patients, 15 to cell saving of pericardial suction blood and residual blood in the CPB circuit after perfusion (cell saver group) vs 14 who received direct retransfusion of the suction blood and the CPB circuit blood (control group). Outcome measures were plasma concentrations of the inflammatory markers interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha, soluble tumor necrosis factor receptors I and II, and procalcitonin at 6, 24, and 72 hours postoperatively. RESULTS At 6 hours postoperatively, the cell saver group displayed significantly reduced plasma levels of IL-6 and IL-8 (p < 0.05). A reduction in IL-10 was also found (p = 0.05), along with nonsignificant reductions in the remaining markers. At 24 and 72 hours, significant differences between groups no longer existed. In the cell saver group, the suction blood and CPB circuit blood were cleared for tumor necrosis factor receptors (p < 0.005), and IL-6, IL-8, IL-10, and procalcitonin were significantly reduced (p < 0.05). Median intraoperative blood loss was 250 mL in the cell saver group vs 475 mL (p < 0.02). Immediately postoperatively the hemoglobin level was higher in the cell saver group (p < 0.03). Transfusion requirements were similar. CONCLUSIONS The cell saver reduced the systemic levels of the proinflammatory markers IL-6 and IL-8 at 6 hours after CPB. The role of the anti-inflammatory molecules IL-10 and soluble tumor necrosis factor receptors is undefined in this setting.

Two Large Preoperative Doses of Erythropoietin Do Not Reduce the Systemic Inflammatory Response to Cardiac Surgery

OBJECTIVES Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB. DESIGN AND SETTING A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital. PARTICIPANTS Patients scheduled for coronary artery bypass graft surgery with CPB. INTERVENTIONS EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS CPB in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p < 0.05) and at 2 hours after CPB increased NT-proBNP (p < 0.05). Also, EPO tended to enhance the CPB-induced increase in IL-1beta receptor antagonist (p = 0.057). Otherwise, EPO had no effect on pro- and antiinflammatory mediators compared with placebo. CONCLUSIONS Two large doses of EPO given shortly before CPB do not reduce perioperative release of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery.

The Nordic Aortic Valve Intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial

BackgroundDegenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting.Methods/DesignThis randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012.DiscussionThe trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis.Trial registrationClinicalTrials.gov: NCT01057173

Graft patency after off-pump versus on-pump coronary artery surgery in high-risk patients

Abstract Objective. To compare angiographic graft patency in high-risk patients randomly allocated to off-pump vs. on-pump coronary artery bypass grafting (CABG). Design. From a randomised, single-centre clinical trial including patients undergoing isolated first-time coronary bypass surgery a subgroup of patients were scheduled to 1-year coronary angiographic follow-up. Patients had 3-vessel disease and a EuroSCORE ≥5. We evaluated graft patency using a patency index (percentage of patent grafts out of the total number of grafts in each patient). Results. One-year angiography was performed in 34 patients undergoing off-pump surgery and 35 patients undergoing on-pump surgery. The mean number of distal anastomoses was 3.38±0.65 in the off-pump group versus 3.46±0.61 in the on-pump group (NS). The number of patients without graft failure was 22 in the off-pump group and 24 in the on-pump group (NS). The overall patency index was 85% in the off-pump group versus 87% in the on-pump group with a mean difference of –2.1%, 95% confidence interval –12.9 to 8.7 (NS). Conclusions. In patients with 3-vessel disease and a high-risk profile we found no statistically significant difference in graft patency between off-pump and on-pump CABG at 1-year coronary angiographic follow-up. Trial registration: ClinicalTrials.gov identifier: NCT00120991.