Ulf Lockowandt

EuroSCORE II dagger

OBJECTIVESnTo update the European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk model.nnnMETHODSnA dedicated website collected prospective risk and outcome data on 22,381 consecutive patients undergoing major cardiac surgery in 154 hospitals in 43 countries over a 12-week period (May-July 2010). Completeness and accuracy were validated during data collection using mandatory field entry, error and range checks and after data collection using summary feedback confirmation by responsible officers and multiple logic checks. Information was obtained on existing EuroSCORE risk factors and additional factors proven to influence risk from research conducted since the original model. The primary outcome was mortality at the base hospital. Secondary outcomes were mortality at 30 and 90 days. The data set was divided into a developmental subset for logistic regression modelling and a validation subset for model testing. A logistic risk model (EuroSCORE II) was then constructed and tested.nnnRESULTSnCompared with the original 1995 EuroSCORE database (in brackets), the mean age was up at 64.7 (62.5) with 31% females (28%). More patients had New York Heart Association class IV, extracardiac arteriopathy, renal and pulmonary dysfunction. Overall mortality was 3.9% (4.6%). When applied to the current data, the old risk models overpredicted mortality (actual: 3.9%; additive predicted: 5.8%; logistic predicted: 7.57%). EuroSCORE II was well calibrated on testing in the validation data subset of 5553 patients (actual mortality: 4.18%; predicted: 3.95%). Very good discrimination was maintained with an area under the receiver operating characteristic curve of 0.8095.nnnCONCLUSIONSnCardiac surgical mortality has significantly reduced in the last 15 years despite older and sicker patients. EuroSCORE II is better calibrated than the original model yet preserves powerful discrimination. It is proposed for the future assessment of cardiac surgical risk.

Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study.

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (nu200a=u200a66/tissue) and atherosclerotic and unaffected arterial wall (nu200a=u200a40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (nu200a=u200a15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (nu200a=u200a3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (nu200a=u200a49/48) and one visceral fat (nu200a=u200a59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (Pu200a=u200a0.008 and Pu200a=u200a0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (nu200a=u200a55/54) relating to carotid stenosis (Pu200a=u200a0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (nu200a=u200a16/17, P<10−27and−30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research.

Guideline for the surgical treatment of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and its prevalence is ∼1-2% of the general population, but higher with increasing age and in patients with concomitant heart disease. The Cox-maze III procedure was a groundbreaking development and remains the surgical intervention with the highest cure rate, but due to its technical difficulty alternative techniques have been developed to create the lesions sets. The field is fast moving and there are now multiple energy sources, multiple potential lesion sets and even multiple guidelines addressing the issues surrounding the surgical treatment of AF both for patients undergoing this concomitantly with other cardiac surgical procedures and also as stand-alone procedures either via sternotomy or via videothoracoscopic techniques. The aim of this document is to bring together all major guidelines in this area into one resource for clinicians interested in surgery for AF. Where we felt that guidance was lacking, we also reviewed the evidence and provided summaries in those areas. We conclude that AF surgery is an effective intervention for patients with all types of AF undergoing concomitant cardiac surgery to reduce the incidence of AF, as demonstrated in multiple randomized studies. There is some evidence that this translates into reduced stroke risk, reduced heart failure risk and longer survival. In addition, symptomatic patients with AF may be considered for surgery after failed catheter intervention or even as an alternative to catheter intervention where either catheter ablation is contraindicated or by patient choice.

Short ischemia causes endothelial dysfunction in porcine coronary vessels in an in vivo model

BACKGROUNDnThe aim of this study was to evaluate the effects of a short period of ischemia (10 mins) and a prolonged period of ischemia (60 mins) followed by reperfusion on coronary flow changes induced by acetylcholine (ACh), adenosine (ADO), and endothelin (ET).nnnMETHODSnThe left anterior descending coronary artery in anesthetized pigs was occluded for 10 or 60 minutes followed by 120 minutes reperfusion. Thereafter, the flow changes in the left anterior descending coronary artery were studied after intracoronary infusion of ACh, ADO, and ET.nnnRESULTSnShort-term ischemia (10 minutes) caused a decrease in vasodilatation, but not the vasoconstriction response to ACh. Prolonged ischemia (60 minutes) impaired ADO induced vasodilatation and aggravated ET evoked vasoconstriction.nnnCONCLUSIONSnThe present findings suggest that a short period of ischemia (10 minutes) causes disturbances of the endothelial regulation of coronary vascular tone and that this endothelial regulation is more sensitive, and precedes changes in vascular smooth muscle function after ischemia and reperfusion.

Editorial Comment: EuroSCORE II and the art and science of risk modelling

Chalmers et al. [4] applied the model to a 5500-patient cohort, concluded that EuroSCORE II is globally better calibrated and found better overall discrimination with a C-statistic of 0.79 (old model 0.77), with best performance in mitral (0.87) and coronary (0.79) surgery and weakest in isolated aortic valve replacement (0.69), marginally better than the old model (0.67). Pooling contemporaneous multi-institutional data provides optimal model validation. A single institution performing exceptionally in one type of surgery may perceive a lack of fit in the entire cohort, as Chalmers indeed found (Hosmer–Lemeshow P-value <0.05) for EuroSCORE II overall, but not in any subdivision. Considering this and other limitations of a single-institution study, the model has achieved its objective of better calibration and discrimination in global cardiac surgery. EuroSCORE II riskstratifies using factors including operation type. Lower discrimination when these are neutralized is therefore unsurprising. We advise caution in applying the model to narrow patient subsets. In the editorials [2, 3], many comments reiterate issues already addressed in the discussion section of the original paper [1]. As Sergeant states, EuroSCORE is widely used and has surgeons’ confidence. There has been misuse, particularly in evaluating patients for transcatheter aortic valve implantation (TAVI), and in predicting non-mortality events. The former is avoidable by our recommendation for using risk-adjusted mortality ratios (RAMR) [1], but that is not enough. Conventional surgery risk factors differ from those of TAVI, and we shall explore our TAVI data to illuminate this. Predicting non-mortality events using EuroSCORE has often succeeded, but its purpose remains to evaluate expeditiously the risk of death. SELECTING AND HANDLING RISK VARIABLES

Arterial patch angioplasty for reconstruction of proximal coronary artery stenosis

BACKGROUNDnOstium patch angioplasty and reconstruction with an onlay patch consisting of pericardium or the saphenous vein is an alternative surgical technique for patients with proximal coronary artery stenosis. Previously described surgical techniques comprise anterior or posterior approaches. In this article we report our experience of using a segment of the proximal right internal mammary artery as an onlay patch for surgical angioplasty.nnnMETHODSnBetween June 1997 and April 1999, 18 patients (9 men and 9 women) were subjected to surgical patch angioplasty of the left main coronary artery, 3 patients had an additional angioplasty performed on the proximal right coronary artery. The first 12 patients were operated with a posterior incision technique, and six subsequent patients by a new technique performed through an oblique incision into the left main stem after transsection of the ascending aorta.nnnRESULTSnAll patients had an uneventful postoperative course, and were fully rehabilitated without clinical symptoms of ischemic heart disease at mean follow-up of 10 months (range 1-23 months). Postoperative catheterization after six days showed excellent results with a widely open and funnel-shaped neoostium.nnnCONCLUSIONSnThe use of a proximal segment of the right internal mammary artery as an onlay patch for reconstructing proximal coronary artery lesions is safe with no complications. Although the posterior approach may be used to obtain excellent results, transsection of the ascending aorta gives an optimal visualization and mobilization of the left main coronary artery when performing surgical angioplasty.

Early results with cardiac support device implant in patients with ischemic and non‐ischemic cardiomyopathy

Objective—To evaluate the possible beneficial echocardiographic, functional and quality of life improving effects of passive containment surgery using the CorCap™ Cardiac Support Device in heart failure patients with dilated cardiomyopathy. Design—Eight patients with dilated cardiomyopathy subjected to cardiac surgery received the Cardiac Support Device. Patients with ischemic cardiomyopathy (nu2005=u20054) underwent coronary artery bypass surgery receiving one to three bypass grafts. In the idiopathic cardiomyopathy group (nu2005=u20054) mitral valve plasty was performed in two patients while two patients received the Cardiac Support Device only. Results—All patients survived the surgery and were discharged to home. There was a gradual, sustained improvement in cardiac dimensions (left ventricular end‐diastolic diameter, left ventricular end‐systolic diameter) and functional improvement (ejection fraction, 6‐min walk, NYHA functional class) as well as quality of life. These beneficial effects developed more rapidly and more extensively in the idiopathic cardiomyopathy group. Conclusion—Addition of the Cardiac Support Device to conventional cardiac surgery, or applied alone, is safe and simple. The device seems to reverse ventricular dilatation and improve functional capacity and well‐being of heart failure patients with dilated cardiomyopathy. Further studies will delineate what patient population will best benefit from passive containment surgery using the CorCap™ Cardiac Support Device.

Myocardial outflow of prostacyclin in relation to metabolic stress during off-pump coronary artery bypass grafting

BACKGROUNDnThe metabolic changes, possible myocardial damage, and influence on the vascular endothelium during off-pump coronary artery bypass grafting have been investigated.nnnMETHODSnCoronary sinus and arterial blood samples were obtained before coronary arterial occlusion, after 10 minutes of ischemia, and after 1 and 10 minutes of reperfusion in 9 patients who had an anastomosis performed to the left anterior descending coronary artery off-pump bypassnnnRESULTSnThe mean ischemic time was 14 +/- 1 minutes. The arteriovenous difference in lactate decreased during ischemia to reach a minimum at 1 minute of reperfusion (-0.15 +/- 0.06 micromol/L compared to 0.21 +/- 10 micromol/L before ischemia; p < 0.01). Myocardial lactate extraction decreased from 14.2 +/- 6.8 micromol/min before ischemia to -10.9 +/- 6.5 micromol/min after 1 minute of reperfusion (p < 0.01). Simultaneously, the arteriovenous difference in 6-keto-PGF(1alpha), the stable metabolite of prostacyclin, decreased from -30 +/- 26 pg/mL to -258 +/- 80 pg/mL at 1 minute of reperfusion (p < 0.05), and the 6-keto-PGF(1alpha) extraction over the heart decreased -556 +/- 466 pg/min to -18,560 +/- 5,683 pg/min (p < 0.01).nnnCONCLUSIONSnThe localized myocardial ischemia associated with these procedures causes changes in the myocardium and endothelial influence. Coronary bypass surgery performed on the beating heart may not be superior in preventing cardiac ischemia and endothelial disturbance, compared with conventional bypass surgery.

Off-pump coronary bypass surgery causes less immediate postoperative coronary endothelial dysfunction compared to on-pump coronary bypass surgery

OBJECTIVEnIn this study a comparison of the vascular reactivity in the coronary circulation was investigated by injection of acetylcholine (ACh) and adenosine (ADO) in coronary bypass patients, operated on with or without the assistance of heart-lung machine. The patients operated on with heart-lung machine were further divided into subjects with stable or unstable angina pectoris.nnnMETHODSnNine patients with stable angina pectoris subjected to off-pump surgery (target arterial occlusion time of 11+/-0.5 min) and 18 patients subjected to on-pump surgery (nine patients with stable angina and nine patients with unstable angina; cross-clamp time of 43+/-3 and 32+/-2 min, respectively), received ACh (10 microg) and ADO (18 microg) given as bolus injections into a vein-graft anastomosed to a coronary vessel. The blood flow in the vein-graft (i.e. indirectly the flow in the targeted coronary circulation) and hemodynamics were observed.nnnRESULTSnIn the off-pump group, ACh evoked an increase with +14+/-12% of control in coronary blood flow, while in the stable on-pump group ACh decreased the blood flow with -60+/-7% of baseline and in the unstable on-pump group the flow was decreased with -38+/-8% of baseline (P<0.001 between the stable on- and off-pump groups, no significant difference between the stable and unstable on-pump groups). ADO significantly increased the coronary blood flow in all three groups; with +81+/-14% in the off-pump patients; with +95+/-14% in the stable on-pump group and with +74+/-13% in the unstable on-pump group (P<0.01 compared to baseline for all three groups). Neither ACh nor ADO injection caused any changes in hemodynamics.nnnCONCLUSIONSnThe present study demonstrates that on-pump coronary bypass surgery appears to be more harmful to the coronary endothelium, in terms of ACh-induced vasoconstriction, compared to off-bypass pump surgery. Furthermore, there is no significant difference in direct smooth muscle vascular reactivity between off-pump and on-pump coronary bypass surgery. No apparent dissimilarities in endothelial dysfunction were observed in the stable and unstable on-pump groups suggesting other causes for differences in post-operative outcome for these patients.

Plasma levels and vascular effects of endothelin and big endothelin in patients with stable and unstable angina pectoris undergoing coronary bypass grafting

OBJECTIVESnThe aim of this study was to determine the plasma and pericardial levels of endothelin-1 (ET-1) and its precursor big endothelin-1 (Big ET-1) in patients with unstable and stable angina prior to and following coronary bypass surgery. To further investigate the content of ET-1, tissue levels were studied in the internal mammary artery (IMA) in patients with stable and unstable angina pectoris. Finally, the difference in reactivity of the IMA to ET-1 and Big ET-1 in stable and unstable patients was evaluated.nnnMETHODSnPlasma and pericardial levels of ET-1 and Big ET-1 were determined with radioimmunoassay in 81 patients (33 unstable) immediately before coronary bypass surgery, and at 6, 14, 40 and 64 h following the procedure. Specimens of the distal IMA from 12 patients (six unstable) were collected at the beginning of surgery for determination of tissue levels of ET-1. Additionally, distal internal mammary arteries were obtained from another 24 patients (12 unstable). These vessels were mounted in organ baths for functional studies on vascular reactivity to ET-1 and Big ET-1.nnnRESULTSnThe peripheral plasma levels of ET-1 in unstable patients were significantly lower in patients with unstable angina compared with patients with stable angina pectoris at all points of measurement. The levels of Big ET-1 were significantly higher pre-operatively in the unstable group, but decreased to similar levels to those of stable patients following coronary bypass grafting. There was no difference in ET-1 tissue content in the IMA between the patients. ET-1 and Big ET-1 caused an endothelin(A) (ET(A))-receptor blocker sensitive, concentration-dependent contraction of the IMA obtained from stable as well as unstable patients.nnnCONCLUSIONSnIt is concluded that unstable angina pectoris is associated with an increased ET-1 turnover. This increased turnover may participate in the local regulation of coronary vascular tone with subsequent influence of the condition of the patients. The present investigation also implies that ET(A)-blockade may be useful as an additional pharmacological principal in the treatment of unstable angina pectoris prior to revascularization, as well as to prevent post-operative arterial graft spasm.