Complete arterial revascularization in multivessel coronary artery disease with 2 conduits (skeletonized grafts and T grafts)

BACKGROUND: Complete arterial CABG is a surgical option to improve long-term results in the treatment of coronary artery disease (CAD). Harvesting of multiple arterial grafts is commonly associated with prolonged operating times and increased trauma. By use of new operative techniques (skeletonized grafts and the T-graft approach), CABG in multivessel CAD is now possible with only 2 grafts. We present our experience in the use of these techniques on a routine basis. METHODS AND RESULTS: Between March 1996 and September 1999, 490 patients (aged 61+/-9 years, 20% female) underwent complete arterial CABG. Left ventricular ejection fraction ranged from 15% to 85% (mean 59+/-15%). Triple-vessel disease was present in 88% of the patients. The incidence of diabetes mellitus was 32% (14% insulin dependent). Either both internal thoracic arteries (ITAs) (23%) or the left ITA and radial artery (77%) were used as conduits. In 85% of the patients, a T graft was created. Mean operating time was 198+/-46 minutes; bypass time, 82+/-25 minutes; and ischemic time, 58+/-22 minutes. Two to 7 (mean 4.1+/-0.9) anastomoses were performed per patient. Perioperative intra-aortic balloon pump was necessary in 12 patients (2.4%). The rate of perioperative myocardial infarction was 1.2%. Sternal complications occurred in 1. 0%, and in-hospital mortality was 2.2%. Postoperative coronary angiography in 172 patients (35%) documented excellent patency rates (left ITA 98.3%, right ITA 96.5%, and radial artery 96.6%). CONCLUSIONS: Complete arterial revascularization in multivessel CAD is possible with the use of only 2 grafts with good perioperative results. This approach allows for complete arterial CABG on a routine basis.

Revascularisation of coronary artery disease in patients with diabetes mellitus

Diabetes mellitus is becoming increasingly prevalent and magnifies the risk of cardiovascular complications. Endothelial dysfunction caused by oxidative stress is a hallmark of diabetes and is responsible for the ubiquitous manifestations of vascular disease in diabetics. Compared with non-diabetic patients, coronary artery disease is more severe and the clinical outcome impaired in diabetic patients undergoing revascularisation. Despite these limitations the benefit of revascularisation therapy is particularly pronounced in diabetics. The optimal revascularisation strategy (coronary artery bypass graft surgery versus percutaneous coronary intervention) in diabetic patients with coronary artery disease depends on clinical and anatomical considerations.

Surgical versus percutaneous revascularization of coronary artery disease in diabetic patients

Morbidity and mortality related to coronary artery disease (CAD) remain a great challenge in patients with diabetes mellitus. Revascularization of CAD is an important therapeutic intervention owing to its impact on both symptoms and prognosis. The optimal revascularization strategy continues to evolve due to the advent of new technologies and improved peri-procedural outcome with both percutaneous coronary interventions and coronary artery bypass grafting. Although clinical outcome following coronary artery bypass is worse in diabetic as opposed to non-diabetic patients, surgical revascularization tends to be associated with better outcome in stable patients with multivessel disease and reduced left ventricular function. The advent of drug-eluting stents has challenged the supremacy of coronary artery bypass grafting and has become a valuable alternative to surgery. The safety and efficacy of drug-eluting stents in the treatment of patients with diabetes and multivessel disease is currently under investigation in several ongoing randomized controlled trials. Percutaneous coronary intervention is the therapy of choice in patients with acute coronary syndromes, particularly ST-elevation myocardial infarction. The focus of this review is to present the current evidence, define the role of percutaneous and surgical revascularization in the treatment of diabetic patients with CAD, and propose a tailored approach for clinical decision-making.

Immunosuppressive treatment for acquired haemophilia: current practice and future directions in Germany, Austria and Switzerland

Acquired haemophilia is an autoimmune disorder characterised by autoantibody formation against coagulation factor VIII. Immunosuppressive treatments including steroids, cytotoxic drugs, rituximab or combinations thereof have been used to eradicate autoantibodies. Very few prospective studies exist evaluating the use of these treatments. Here, we performed a survey among 73 physicians from 57 haemophilia treatment centres in order to describe current practice patterns and critical issues for future research in acquired haemophilia. The results demonstrate a high diversity of first- and second-line treatments. Factors influencing treatment decision were underlying disorder, severity of bleeding and inhibitor titre. Frequently used first-line treatments were steroids plus cyclophosphamide (44%) and steroids alone (11%). Second-line treatment was most often rituximab (30%), with or without steroids and/or cyclophosphamide. Most participants indicated to change from first- to second-line treatment after 4 weeks in case of failure to obtain partial remission (31%), continued bleeding (40%) or continued severe bleeding requiring bypass treatment (59%). Immunoadsorption was preferred for first- and second-line treatment by 10% and 9% of participants, respectively. These results highlight critical issues in the field. Open questions and directions for future research are discussed.

Perioperative anaesthetic management of mediastinal mass in adults

Mediastinal mass syndrome remains an anaesthetic challenge that cannot be underestimated. Depending on the localization and the size of the mediastinal tumour, the clinical presentation is variable ranging from a complete lack of symptoms to severe cardiorespiratory problems. The administration of general anaesthesia can be associated with acute intraoperative or postoperative cardiorespiratory decompensation that may result in death due to tumour-related compression syndromes. The role of the anaesthesiologist, as a part of the interdisciplinary treatment team, is to ensure a safe perioperative period. However, there is still no structured protocol available for perioperative anaesthesiological procedure. The aim of this article is to summarize the genesis of and the diagnostic options for mediastinal mass syndrome and to provide a solid detailed methodology for its safe perioperative management based on a review of the latest literature and our own clinical experiences. Proper anaesthetic management of patients with mediastinal mass syndrome begins with an assessment of the preoperative status, directed foremost at establishing the localization of the tumour and on the basis of the clinical and radiological findings, discerning whether any vital mediastinal structures are affected. We have found it helpful to assign 'severity grade' (using a three-grade clinical classification scale: 'safe', 'uncertain', 'unsafe'), whereby each stage triggers appropriate action in terms of staffing and apparatus, such as the provision of alternatives for airway management, cardiopulmonary bypass and additional specialists. During the preoperative period, we are guided by a 12-point plan that also takes into account the special features of transportation into the operating theatre and patient monitoring. Tumour compression on the airways or the great vessels may create a critical respiratory and/or haemodynamic situation, and therefore the standard of intraoperative management includes induction of anaesthesia in the operating theatre on an adjustable surgical table, the use of short-acting anaesthetics, avoidance of muscle relaxants and maintenance of spontaneous respiration. In the case of severe clinical symptoms and large mediastinal tumours, we consider it absolutely essential to cannulate the femoral vessels preoperatively under local anaesthesia and to provide for the availability of cardiopulmonary bypass in the operating theatre, should extracorporeal circulation become necessary. The benefits of establishing vascular access under local anaesthesia clearly outweigh any associated degree of patient discomfort. In the case of patients classified as 'safe' or 'uncertain', a preoperative consensus with the surgeons should be reached as to the anaesthetic approach and the management of possible complications.

[Neuromonitoring and neuroprotection in cardiac anaesthesia. Nationwide survey conducted by the Cardiac Anaesthesia Working Group of the German Society of Anaesthesiology and Intensive Care Medicine]

OBJECTIVE: The primary objective of this nationwide survey carried out in department of cardiac anesthesia in Germany was to identify current practice with regard to neuromonitoring und neuroprotection. METHODOLOGY: The data are based on a questionnaire sent out to all departments of cardiac anesthesia in Germany between October 2007 und January 2008. The anonymized questionnaire contained 26 questions about the practice of preoperative evaluation of cerebral vessels, intra-operative use of neuromonitoring, the nature und application of cerebral protective measures, perfusion management during cardiopulmonary bypass, postoperative evaluation of neurological status, and training in the field of cerebral monitoring. RESULTS: Of the 80 mailed questionnaires 55% were returned and 90% of department evaluated cerebral vessels preoperatively with duplex ultrasound. The methods used for intra-operative neuromonitoring are electroencephalography (EEG, 60%) for type A dissections (38.1%), for elective surgery on the thoracic and thoraco-abdominal aorta (34.1% and 31.6%, respectively) and in carotid surgery (43.2%) near infrared spectroscopy (40%), evoked potentials (30%) and transcranial Doppler sonography (17.5%), with some centers using combined methods. In most departments the central nervous system is not subjected to monitoring during bypass surgery, heart valve surgery, or minimally invasive surgery. Cerebral protective measures used comprise patient cooling on cardio-pulmonary bypass (CPB 100%), extracorporeal cooling of the head (65%) and the administration of corticosteroids (58%), barbiturates (50%) and antiepileptic drugs (10%). Neuroprotective anesthesia consists of administering inhalation anesthetics (32.5%; sevoflurane 76.5%) and intravenous anesthesia (20%; propofol and barbiturates each accounting for 46.2%). Of the departments 72.5% cool patients as a standard procedure for surgery involving cardiovascular arrest and 37.5% during all surgery using CPB. In 84.6% of department CPB flow equals calculated cardiac output (CO) under normothermia, while the desired mean arterial pressure (MAP) varies between 60 and 70 mmHg (43.9%) and between 50 and 60 mmHg (41.5%), respectively. At body temperatures less than 18 degrees C CPB flow is reduced below the calculated CO (70%) while 27% of departments use normothermic flow rates. The preferred MAP under hypothermia is between 50 and 60 mmHg (59%). The results of intra-operative neuromonitoring are documented on the anesthesia record (77%). In 42.5% of the departments postoperative neurological function is estimated by the anesthesiologist. Continuing education sessions pertaining to neuromonitoring are organized on a regular basis in 32.5% of the departments and in 37.5% individual physicians are responsible for their own neuromonitoring education. CONCLUSION: The present survey data indicate that neuromonitoring and neuroprotective therapy during CPB is not standardized in cardiac anesthesiology departments in Germany. The systemic use of available methods to implement multimodal neuromonitoring would be desirable.

Human internal thoracic arteries from diabetic patients are resistant to endothelial dysfunction

The aim of this analysis was to compare vasoreactive properties of internal thoracic arteries (ITA) grafts from diabetic (DM) to those of non-diabetic (ND) patients. Ring segments of ITA, taken from patients undergoing coronary artery bypass grafting, were suspended in organ bath chambers filled with modified Krebs-Henseleit solution and contractile responses to potassium chloride (KCl), noradrenaline (NA), endothelin-1 (ET-l), and endothelium-dependent relaxant responses to acetylcholine (ACH) were recorded isometrically. The receptor-mediated agonists NA and ET-1 stimulated ITA from both groups within similar concentration ranges while ITA from DM patients proved to be significantly more sensitive to KCl than ITA from ND. Furthermore, maximal contractile responses indicated that KCl (3.79 +/- 0.30 g, n = 7 in DM and 2.50 +/- 0.23 g, n = 29 in ND, P < 0.05) evoked significantly higher responses in ITA from DM as compared to the ND control group while both NA and ET-l stimulated ITA from both groups with similar efficacies. Endothelium-dependent relaxant responses to ACH proved to be similar in both groups when expressed as percentages of the pre-existing tone. The present data support the contention that in comparison to ND controls arteries from DM patients are more sensitive to depolarization but endothelial dysfunction is less frequent in human ITA than expected from observations in systemic vascular beds.

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial

OBJECTIVE: Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. DESIGN:: Double-blind, randomized, placebo-controlled trial. SETTING: One Swiss University Hospital. PATIENTS: One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. MEASUREMENTS AND MAIN RESULTS: The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. CONCLUSION: This negative or, because of methodologic issues, possibly failed trial does not support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass.

Massive intraoperative thrombus of the aortic arch and proximal descending aorta

A 49-year-old male patient presented with a paravalvular leakage 18 years after aortic valve replacement. The patient received a mechanical valve and was weaned uneventfully from cardiopulmonary bypass. After a drop in the pressure curve of the left radial artery an additional line was placed in the proximal ascending aorta showing normal systemic pressure. Transesophageal echocardiography showed a massive circular thrombosis of the distal aortic arch. The patient received a covered stent to expand the residual aortic lumen and left the hospital in good health.

Retaining perivascular tissue of human saphenous vein grafts protects against surgical and distension-induced damage and preserves endothelial nitric oxide synthase and nitric oxide synthase activity

OBJECTIVE: Conventional harvesting of saphenous vein used for coronary artery bypass surgery induces a vasospasm that is overcome by high-pressure distension. Saphenous vein harvested with its cushion of perivascular tissue by a "no touch" technique does not undergo vasospasm and distension is not required, leading to an improved graft patency. The aim of this study is to investigate the effect of surgical damage and high-pressure distension on endothelial integrity and endothelial nitric oxide synthase expression and activity in saphenous vein harvested with and without perivascular tissue. METHODS: Saphenous veins from patients (n = 26) undergoing coronary artery bypass surgery were prepared with and without perivascular tissue. We analyzed the effect of 300 mm Hg distension on morphology and endothelial nitric oxide synthase/nitric oxide synthase activity using a combination of immunohistochemistry, Western blot analysis, reverse transcriptase polymerase chain reaction, and enzyme assay in distended (with and without perivascular tissue) compared with nondistended (with and without perivascular tissue) segments. RESULTS: Distension induced substantial damage to the luminal endothelium (assessed by CD31 staining) and vessel wall. Endothelial nitric oxide synthase expression and activity were significantly reduced by high-pressure distension and removal of, or damage to, perivascular tissue. The effect of distension was significantly less for those with perivascular tissue than for those without perivascular tissue in most cases. CONCLUSION: The success of the saphenous vein used as a bypass graft is affected by surgical trauma and distension. Veins removed with minimal damage exhibit increased patency rates. We show that retention of perivascular tissue on saphenous vein prepared for coronary artery bypass surgery by the "no touch" technique protects against distension-induced damage, preserves vessel morphology, and maintains endothelial nitric oxide synthase/nitric oxide synthase activity.

UsedSoft and the Big Bang Theory: Is the e-Exhaustion Meteor about to Strike?

Since the UsedSoft ruling of the CJEU in 2012, there has been the distinct feeling that – like the big bang - UsedSoft signals the start of a new beginning. As we enter this brave new world, the Copyright Directive will be read anew: misalignments in the treatment of physical and digital content will be resolved; accessibility and affordability for consumers will be heightened; and lock-in will be reduced as e-exhaustion takes hold. With UsedSoft as a precedent, the Court can do nothing but keep expanding its own ruling. For big bang theorists, it is only a matter of time until the digital first sale meteor strikes non-software downloads also. This paper looks at whether the UsedSoft ruling could indeed be the beginning of a wider doctrine of e-exhaustion, or if it is simply a one-shot comet restrained by provisions of the Computer Program Directive on which it was based. Fighting the latter corner, we have the strict word of the law; in the UsedSoft ruling, the Court appears to willingly bypass the international legal framework of the WCT. As far as expansion goes, the Copyright Directive was conceived specifically to implement the WCT, thus the legislative intent is clear. The Court would not, surely, invoke its modicum of creativity there also... With perhaps undue haste in a digital market of many unknowns, it seems this might well be the case. Provoking the big bang theory of e-exhaustion, the UsedSoft ruling can be read as distinctly purposive, but rather than having copyright norms in mind, the standard for the Court is the same free movement rules that underpin the exhaustion doctrine in the physical world. With an endowed sense of principled equivalence, the Court clearly wishes the tangible and intangible rules to be aligned. Against the backdrop of the European internal market, perhaps few legislative instruments would staunchly stand in its way. With firm objectives in mind, the UsedSoft ruling could be a rather disruptive meteor indeed.

Type A aortic dissection after nonaortic cardiac surgery

BACKGROUND Cardiac surgery with cardiopulmonary bypass is associated with mechanical manipulation of the ascending aorta that occasionally leads to type A aortic dissection (AAD). METHODS AND RESULTS One hundred three patients with surgical repair for AAD following nonaortic cardiac surgery were identified. With the use of logistic regression modeling, coronary artery bypass surgery (CABG), either isolated or combined with another procedure in the initial operation, was associated with significantly higher operative mortality in comparison with patients with non-CABG procedures at the time of AAD repair both for all patients (odds ratio, 2.90; 95% confidence interval, 1.09-7.72; P=0.033) and for patients with acute and chronic AAD≥30 days after the initial operation (odds ratio, 3.62; 95% confidence interval, 1.13-11.54; P=0.03). In patients who developed AAD late after the initial operation, operative mortality was highest in patients without preoperative coronary angiography and appropriate management of their native coronary artery disease and graft disease (odds ratio, 5.36; 95% confidence interval, 1.68-17.0; P=0.002). Nearly all the intimal dissection tears were located at sites of previous surgical trauma. Most of the ascending aortas that had dissected initially had a diameter≥40 mm with histological evidence of medial degeneration in resected tissue samples. CONCLUSIONS In patients who have undergone previous cardiac surgery, preexisting aortic wall pathology contributes to AAD with typical intimal damage at sites of mechanical trauma. The operative mortality was the highest in patients with previous CABG in comparison with patients with non-CABG procedures. Preoperative coronary angiography and operative management of native coronary and graft disease were significantly associated with outcome in patients with previous CABG.

Artemisinin, an endoperoxide antimalarial, disrupts the hemoglobin catabolism and heme detoxification systems in malarial parasite

Endoperoxide antimalarials based on the ancient Chinese drug Qinghaosu (artemisinin) are currently our major hope in the fight against drug-resistant malaria. Rational drug design based on artemisinin and its analogues is slow as the mechanism of action of these antimalarials is not clear. Here we report that these drugs, at least in part, exert their effect by interfering with the plasmodial hemoglobin catabolic pathway and inhibition of heme polymerization. In an in vitro experiment we observed inhibition of digestive vacuole proteolytic activity of malarial parasite by artemisinin. These observations were further confirmed by ex vivo experiments showing accumulation of hemoglobin in the parasites treated with artemisinin, suggesting inhibition of hemoglobin degradation. We found artemisinin to be a potent inhibitor of heme polymerization activity mediated by Plasmodium yoelii lysates as well as Plasmodium falciparum histidine-rich protein II. Interaction of artemisinin with the purified malarial hemozoin in vitro resulted in the concentration-dependent breakdown of the malaria pigment. Our results presented here may explain the selective and rapid toxicity of these drugs on mature, hemozoin-containing, stages of malarial parasite. Since artemisinin and its analogues appear to have similar molecular targets as chloroquine despite having different structures, they can potentially bypass the quinoline resistance machinery of the malarial parasite, which causes sublethal accumulation of these drugs in resistant strains.

Severe aortic stenosis and coronary artery disease

Coronary artery disease (CAD) and aortic stenosis (AS) share pathophysiological mechanisms and risk factors. Moreover, the prevalence of CAD increases among elderly patients with severe AS since disease progression is strongly associated with age for both CAD and AS. These factors contribute to the frequent coexistence of CAD and AS. Patients with concomitant AS and CAD are characterised by higher baseline risk profiles with a larger number of comorbidities as compared to patients with isolated AS. Therefore, adequate therapeutic strategies are crucial for the treatment of these patients. The number of patients undergoing concomitant coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) doubled during the last decade. Moreover, the development and rapid integration of transcatheter aortic valve implantation (TAVI) into clinical practice in western European countries has further extended invasive treatment of AS to elderly high-risk patients not considered suitable candidates for SAVR, frequently presenting with CAD. The aim of this review article is to provide an overview on CAD prevalence, impact on clinical outcomes, and treatment strategies in patients with severe AS requiring SAVR or TAVI.