Does hypothermic circulatory arrest or prolonged cardiopulmonary bypass time affect early outcome in reoperative aortic surgery?

AIM: Prolonged cardio-pulmonary bypass (CPB) time, usually necessary for reoperations, is known to increase mortality in coronary bypass procedures and aortic reoperations. We investigated if prolonged CPB time and arch reconstruction in reoperations of the thoracic aorta affect in-hospital outcome. METHODS: Twenty-nine patients underwent reoperations on the thoracic aorta. The reoperations performed were aortic root replacement with composite graft without aortic arch involvement in ten patients, isolated ascending aorta replacement in six patients, aortic arch replacement as a primary procedure in two patients, and aortic arch in conjunction with ascending or descending aorta replacement in 11 patients. RESULTS: Fourteen patients had aortic reoperation with deep hypothermic circulatory arrest (DHCA) and 15 without DHCA. The in-hospital mortality rate was 13.8%. The use deep hypothermic circulatory arrest or CPB time did not affect early outcome. Previous coronary artery bypass procedure was independent predictor of in-hospital mortality. Seven patients required re-exploration for bleeding. One patient suffered from stroke and finally five patients had prolonged ventilation, two requiring tracheostomy. There have been no deaths in the follow-up period. None of the patients has required repeat surgical intervention on the heart or the aorta. CONCLUSION: The use of DHCA or prolonged CPB time do not affect early outcome in reoperations of the thoracic aorta.

Pericardiocentesis guided by a pulse generator.

This study was performed to compare pericardiocentesis guided by a pacing current applied through the pericardiocentesis needle with the traditional method of monitoring ST segment elevation from the needle tip electrogram. ST segment elevation was measured at 3 mm from the epicardium, after epicardial contact, after epicardial penetration and again at 3 mm from the epicardium after epicardial penetration. Two millivolts of ST segment elevation gave the highest combined positive (86%) and negative (79%) predictive value for epicardial contact by the pericardiocentesis needle between the two groups with the largest difference: 3 mm from the epicardium before contact and after epicardial penetration. Therefore, ST segment monitoring cannot reliably determine the point of epicardial contact. To determine the optimal stimulus strength for pulse generator-guided pericardiocentesis, pacing studies were performed using 2, 4, 6, 8 and 10 mA unipolar stimulus strengths. The pacing studies were performed both with and without a hemodynamically significant pericardial effusion to determine if increased pericardial pressure altered the pacing threshold. A 4 mA unipolar cathodal stimulus was chosen because it captured the ventricle only with direct contact of the epicardium. Ten dogs were instrumented and cardiac tamponade produced so that a subxiphoid approach to the epicardium with the pacing needle electrode could be attempted. During pericardiocentesis, needle tip electrograms were recorded, alternating with pacing attempts using a 4 mA unipolar stimulus. In all 10 dogs, the effusion was entered and epicardium was contacted as indicated by capture. No myocardial perforation or coronary artery or venous injuries were produced. These findings support the use of a pulse generator to guide pericardiocentesis.

Single-stage extensive replacement of the thoracic aorta: the arch-first technique.

BACKGROUND: Single-stage extensive replacement of the thoracic aorta usually involves a period of circulatory arrest with performance of the graft-to-lower descending thoracic aorta anastomosis before performing the anastomosis to the arch vessels. To minimize the period of brain ischemia and reduce the potential for neurologic injury, we developed an alternative technique. METHODS: In 6 patients with extensive aneurysms involving the entire thoracic aorta, exposure was obtained via a bilateral thoracotomy in the anterior fourth intercostal space with transverse sternotomy. A 10-mm graft was anastomosed to the aortic graft, opposite the site of the planned anastomosis to the arch vessels. During a single period of circulatory arrest (34-46 minutes), the aortic graft was attached to a cuff of aorta containing the arch vessels. The graft was then clamped on either side, and the arch was perfused with cold blood for 20 to 36 minutes. After the distal aortic anastomosis was completed, antegrade perfusion was established via the 10-mm graft. The proximal aortic anastomosis was performed last. RESULTS: No patient sustained a permanent neurologic deficit. All 6 patients were discharged from the hospital. CONCLUSIONS: The "arch-first" technique, combined with a bilateral transverse thoracotomy, allows expeditious replacement of the thoracic aorta with an acceptable interval of hypothermic circulatory arrest and minimizes the risk of retrograde atheroembolism by establishing antegrade perfusion.

Single-stage reoperative repair of chronic type A aortic dissection by means of the arch-first technique.

OBJECTIVE: Management of the enlarged, chronically dissected aorta after previous repair of acute aortic dissection or after a previous cardiac operation may present a formidable technical challenge. Marked enlargement of the proximal descending thoracic aorta precludes safe use of staged procedures, including the elephant trunk technique. METHODS: Sixteen patients with chronic type A aortic dissection (mean age, 56 years) underwent resection of the ascending aorta, the aortic arch, and varying segments of the descending thoracic aorta. We used single-stage replacement, with perfusion of the aortic arch first to minimize the duration of brain ischemia, with a bilateral anterior thoracotomy (clamshell) incision. Eleven patients had undergone previous repair of acute type A dissection. Five patients had type A dissection after aortic valve replacement (2 patients) and coronary artery bypass (3 patients). Marked enlargement of the aorta distal to the left subclavian artery precluded a 2-stage repair. The mean interval between the initial and reoperative procedures was 62 months (range, 5-137 months). RESULTS: There was 1 (6.2%; 70% confidence limits, 0.3%-24.7%) hospital death. Four patients required reoperation for bleeding. One patient required a right ventricular assist device that was successfully removed. Six patients required assisted ventilation for more than 72 hours, and 3 patients required a tracheostomy. All were successfully weaned from ventilatory support. No patient had a stroke or other adverse neurologic outcome. CONCLUSION: The single-stage, arch-first replacement technique is a safe and effective procedure for patients who require extensive reoperations for chronic expanding type A dissection.

Cryoablation of ventricular tachycardia guided by return cycle mapping after entrainment.

BACKGROUND: Although the implantable cardioverter-defibrillator effectively prevents sudden cardiac death, patients are still prone to recurrence of ventricular tachyarrhythmias. Electrophysiologically guided surgery is the most effective modality in abolishing ventricular tachycardia, having a lower recurrence rate than pharmacologic therapy or catheter ablation. Return cycle mapping after entrainment has been shown to localize the central common pathway, which is the target region for ablation, without pacing at the pathway or recording the potentials from the pathway. METHODS: To determine the accuracy and usefulness of return cycle mapping in surgery for ventricular tachycardia, we cryoablated 8 morphologies of ventricular tachycardia induced in postinfarction dogs with the guidance of return cycle mapping. The ventricular tachycardia was entrained from 3 to 5 different epicardial sites at a paced cycle length 10 to 20 ms shorter than the ventricular tachycardia cycle length and the epicardium was mapped with 61 unipolar electrodes during cessation of entrainment to construct return cycle maps. The return cycle was determined by subtracting the first activation time from the second activation time after the last stimulus in each electrode location, and the maps were then displayed on a computer. RESULTS: The total analysis process was completed within 3 minutes by means of a computer with custom-made programs. The activation map during ventricular tachycardia did not localize the central common pathway in any morphology of ventricular tachycardia, because the pattern of activation was concentric and diastolic potentials were not recorded. Cryoablation of the region where the isotemporal lines of the return cycle equal to the ventricular tachycardia cycle length intersected resulted in termination of ventricular tachycardia in all morphologies. The intersection was 26 +/- 9 mm from the earliest activation site. Epicardial mapping with 253 electrodes during cryothermia showed that the region localized by return cycle mapping was the central common pathway sandwiched between the lines of conduction block and that the cryolesion connected the lines of block, blocked the rotating wave front, and resulted in termination of the ventricular tachycardia. CONCLUSION: Return cycle mapping provides an accurate and rapid means of localizing the central common pathway without the need for recording potentials from the pathway or pacing at the pathway in ablation for ventricular tachycardia.

Profound systemic hypothermia protects the spinal cord in a primate model of spinal cord ischemia.

Spinal cord ischemia with resultant paraplegia or paraparesis remains an important clinical problem after operations on the thoracoabdominal aorta. Because hypothermia has a protective effect on ischemic neural tissue, we developed a baboon model of spinal cord ischemia to simulate the situation encountered clinically for resection of aneurysms of the thoracoabdominal aorta and to determine whether profound hypothermia produced by hypothermic cardiopulmonary bypass has a protective effect on spinal cord function. After cardiopulmonary bypass was established, the aorta was clamped distal to the left subclavian artery and proximal to the renal arteries for 60 minutes. Group I animals (n = 9) underwent aortic clamping at normothermia (37 degrees C), and group II animals (n = 9) were cooled to a rectal temperature of 15 degrees C before aortic clamping and underwent cardiopulmonary bypass at this temperature until the aorta was unclamped. Of the eight operative survivors in group I, six animals were paraplegic and two were paraparetic, whereas all six group II animals that survived the procedure were neurologically intact (p = 0.0002). The protective effect of hypothermia was associated with blunting of the hyperemic response of spinal cord blood flow (determined by the radioactive microsphere technique) in the lower thoracic and the lumbar segments of the spinal cord after unclamping of the aorta. Profound hypothermia produced by hypothermic cardiopulmonary bypass may be an effective method of protection of the spinal cord in patients undergoing repair of aneurysms of the thoracoabdominal aorta and may reduce the prevalence of ischemic injury to the spinal cord.

Functional and oximetric assessment of patients after lung reduction surgery.

OBJECTIVE: The goal of this study was to clarify the issue of functional oxygen requirement by regimented exercise oximetry in patients undergoing lung reduction surgery. METHODS: Thirty-seven patients underwent lung reduction surgery and were followed up for at least 3 months. Patients routinely completed a 6-week program of cardiopulmonary rehabilitation. Preoperative and postoperative spirometry, dyspnea scores, 6-minute walk distances, respiratory mechanics, and exercise oximetry were recorded. RESULTS: After the operation, patients had a 37% increase in forced vital capacity and a 59% increase in forced expiratory volume in 1 second. Six-minute walk distance increased from 913 +/- 310 feet before the lung reduction operation to 1202 +/- 274 feet 6 months after the operation (p < 0.001). Maximal inspiratory and expiratory pressures were significantly increased in 16 patients after lung reduction surgery. Perceived dyspnea was significantly improved. Exercise pulse oximetry demonstrated that 83% of patients met American Thoracic Society criteria for supplemental oxygen use before lung reduction surgery. After the operation, 70% of patients continued to meet American Thoracic Society criteria for supplemental oxygen use. Notably, 10 patients with exertional desaturation while breathing room air discontinued supplemental oxygen use because of a reduction in dyspnea. CONCLUSIONS: These findings demonstrate significant subjective and functional improvements related to lung reduction surgery. Exercise-induced hypoxia was not reversed by lung reduction surgery. Discontinuance of supplemental oxygen use owing to reduction in dyspnea and improved physical performance may not be warranted in lieu of continued exertional desaturation.

Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia.

Profound hypothermia induced with cardiopulmonary bypass has a protective effect on spinal cord function during operations on the thoracoabdominal aorta. The mechanism of this protection remains unknown. It has been proposed that the release of excitatory amino acids in the extracellular space plays a causal role in irreversible neuronal damage. We investigated the changes in extracellular neurotransmitter amino acid concentrations with the use of in vivo microdialysis in a swine model of spinal cord ischemia. All animals underwent left thoracotomy and right atrium-femoral artery cardiopulmonary bypass with additional aortic arch perfusion. Lumbar laminectomies were then done and microdialysis probes were inserted stereotactically in the anterior horn of the second and fourth segments of the lumbar spinal cord. The probes were perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min and 15-minute samples were assayed by high-performance liquid chromatography. Group 1 animals (n = 6) underwent aortic clamping distal to the left subclavian artery and proximal to the renal arteries for 60 minutes at normothermia (37 degrees C) and group 2 animals (n = 5) were cooled to a rectal temperature of 20 degrees C before application of aortic clamps, maintained at this level during cardiopulmonary bypass until the aorta was unclamped, and then slowly rewarmed to 37 degrees C. Seven amino acids were studied, including two excitatory neurotransmitters (glutamate and aspartate) and five putative inhibitory neurotransmitters (glycine, gamma-aminobutyric acid, serine, adenosine, and taurine). Glutamate exhibited a threefold increase in extracellular concentration during normothermic ischemia compared with baseline values and remained elevated until 60 minutes after reperfusion. The increase in aspartate concentration was not significant. The extracellular concentrations of glycine and gamma-aminobutyric acid also increased significantly during ischemia and reperfusion. Hypothermia uniformly prevented the release of amino acids in the extracellular space. Glutamate levels remained significantly decreased even after rewarming to normothermia whereas glycine levels returned to baseline values. These results are consistent with a role for excitatory amino acids in the production of ischemic spinal cord injury and suggest that the mechanism of hypothermic protection may be related to decreased release of these amino acids in the ischemic spinal cord.

Hypothermic cardiopulmonary bypass for spinal cord protection: rationale and clinical results.

BACKGROUND: Hypothermic cardiopulmonary bypass with or without circulatory arrest has been used successfully for the treatment of complex aneurysms of the descending thoracic and thoracoabdominal aorta. Hypothermia has a protective effect on spinal cord function, and its use has been associated with a low incidence of paraplegia in traditionally high-risk patients. Experimentally, the protective effect of hypothermia has been related to amelioration of excitotoxic injury by reduction of neurotransmitter release and to inhibition of delayed apoptotic cell death. METHODS: During a 12-year period, 114 patients with descending thoracic or thoracoabdominal aortic disease underwent replacement of the involved aortic segments using hypothermic cardiopulmonary bypass and intervals of circulatory arrest. RESULTS: The hospital mortality was 8% (9 patients). Paraplegia occurred in 2 and paraparesis in 1 of the 108 patients whose lower limb function was assessed postoperatively (2.8%). None of 40 patients with aortic dissection and none of the last 81 patients in the series developed paralysis. CONCLUSIONS: Our experience with hypothermic cardiopulmonary bypass and circulatory arrest confirms that hypothermia provides substantial protection against paraplegia, and it allows complex operations on the descending thoracic and thoracoabdominal aorta to be performed with acceptable mortality.

Hypothermic bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.

BACKGROUND: Hypothermic cardiopulmonary bypass with intervals of circulatory arrest is a useful adjunct during operations on the descending thoracic aorta and distal aortic arch when severe aortic disease precludes placement of clamps on the aorta. Hypothermia also has a marked protective effect on spinal cord function during periods of aortic occlusion. METHODS: Fifty-one patients (age range, 22 to 79 years) with descending thoracic or thoracoabdominal aortic disease had resection and graft replacement of the diseased aortic segments using hypothermic cardiopulmonary bypass and intervals of circulatory arrest in situations where the location, extent, or severity of disease precluded placement of clamps on the proximal aorta (8 patients) or (in 43 patients) when extensive thoracic (11) or thoracoabdominal (32) aortic disease was present and the risk for development of spinal cord ischemic injury and renal failure was judged to be increased. Patent intercostal (below T-6) and upper lumbar arteries were attached to the graft whenever possible. RESULTS: Thirty-day mortality was 9.8% (5 patients). Paraplegia occurred in 2 and paraparesis in 1 of the 46 30-day survivors (6.5%). Among the 27 operative survivors with thoracoabdominal aneurysms, paraplegia occurred in 1 of 12 with Crawford type I (8%), 0 of 10 with type II, and 1 of 5 with type III aneurysms (20%). Paraplegia occurred in none of the 12 patients with aortic dissection and in 2 of the 15 patients with degenerative aneurysms. Renal failure requiring dialysis occurred in 1 (2.2%) of the 46 30-day survivors. CONCLUSIONS: Hypothermic circulatory arrest is a valuable adjunct for the treatment of complex aortic disease involving the aortic arch and thoracoabdominal aorta. In patients with thoracoabdominal aneurysms, its use has been associated with a low incidence of renal failure and an incidence of paraplegia/paraparesis in traditionally high-risk subsets (type I and II aneurysms, aortic dissection), which may be less than that observed with other surgical techniques.

Dextrorphan inhibits the release of excitatory amino acids during spinal cord ischemia.

The release of excitatory amino acids, particularly glutamate, into the extracellular space plays a causal role in irreversible neuronal damage after central nervous system ischemia. Dextrorphan, a noncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to provide significant protection against cerebral damage after focal ischemia. We investigated the changes in extracellular neurotransmitter amino acid concentrations using in vivo microdialysis in a swine model of spinal cord ischemia. After lumbar laminectomies were performed, all animals underwent left thoracotomy and right atrial-femoral cardiopulmonary bypass with additional aortic arch perfusion. Microdialysis probes were then inserted stereotactically into the lumbar spinal cord. The probes were perfused with artificial cerebrospinal fluid and 15-minute samples were assayed using high-performance liquid chromatography. Group 1 animals (n = 9) underwent aortic clamping distal to the left subclavian and proximal to the renal arteries for 60 minutes. Group 2 animals (n = 7) were treated with dextrorphan before application of aortic clamps, and during aortic occlusion and reperfusion. Five amino acids were studied, including two excitatory neurotransmitters (glutamate and aspartate) and three putative inhibitory neurotransmitters (glycine, gamma-amino-butyric acid, and serine). Somatosensory-evoked potentials and motor-evoked potentials were monitored. Glutamate exhibited a threefold increase in extracellular concentration during normothermic ischemia compared with baseline values and remained elevated until 60 minutes after reperfusion. In animals treated with dextrorphan, glutamate concentrations decreased to one-third of baseline levels before aortic clamping and remained unchanged during ischemia and reperfusion. There was early loss of somatosensory-evoked potentials and motor-evoked potentials during ischemia in group 1 animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and efficacy of hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.

BACKGROUND: Hypothermic cardiopulmonary bypass with circulatory arrest is an important adjunct for operations on the distal aortic arch and the descending thoracic and thoracoabdominal aorta. Its safety and efficacy compared with other techniques (eg, simple aortic clamping, partial cardiopulmonary bypass, and regional hypothermia) are not clearly established. METHODS: One hundred sixty-one patients (ranging from 20 to 83 years old) with descending thoracic or thoracoabdominal aortic disease had resection and graft replacement of the involved aortic segments using hypothermic cardiopulmonary bypass usually with intervals of circulatory arrest (mean interval, 38 minutes). RESULTS: The 30-day mortality rate was 6.2% (10 patients). It was 41% (7 of 17) for patients having emergent operations (rupture or acute dissection) and 2.1% (3 of 144) for all other patients (p < 0.001). The 90-day mortality rate was 11.8% (19 patients). Paraplegia occurred in 4 and paraparesis in 1 of the 156 operative survivors whose lower limb function could be assessed postoperatively (3.2%). Among the 91 survivors with thoracoabdominal aortic disease, early paraplegia occurred in 1 of 33 patients with Crawford type I disease, 0 of 34 with type II disease, and 2 of 24 with type III disease. One patient (type II disease) had development of paraplegia on the tenth postoperative day. None of the 50 patients with aortic dissection experienced paralysis. Renal dialysis was required in 4 (2.5%) of the 157 operative survivors, prolonged inotropic support (> 48 hours) in 17 (11%), reoperation for bleeding in 8 (5%), mechanical ventilation (> 48 hours) in 31 (20%), and tracheostomy in 13 (8%). Three patients (1.9%) sustained a stroke. CONCLUSIONS: Hypothermic cardiopulmonary bypass provides safe and substantial protection against paralysis and renal, cardiac, and visceral organ system failure that equals or exceeds that of other currently used techniques but without the need of other adjuncts.

Human ventricular tachycardia: precise intraoperative localization with potential distribution mapping.

Electrophysiologically guided operations for ventricular tachycardia (VT) have been directed exclusively by activation time maps. Even with computer-assisted mapping, extensive editing is required, which prolongs the duration of the operation and which may introduce significant error. In contrast, potential distribution maps can be constructed in less than 3 minutes and can be viewed as a movie of developing and receding potentials. In 4 patients undergoing operation for VT, endocardial mapping was performed using form-fitting electrodes containing 160 points. A computerized mapping system, capable of simultaneously recording 256 channels of data, was used to analyze data and to display potential distribution maps sequentially at 1-millisecond intervals as a color movie. A total of eight morphologies of sustained VT were mapped. The mean VT cycle length was 340 +/- 40 milliseconds (range, 274 to 394 milliseconds). In 3 patients with ischemic heart disease, four VT morphologies originated from the subendocardium. All were successfully ablated with cryoablation alone or in conjunction with aneurysmectomy and endocardial resection. A fourth patient with VT secondary to cardiomyopathy had multiple morphologies and received an implantable cardioverter defibrillator. Potential distribution maps correlated well with the concomitant activation time maps. Thus, potential distribution mapping provides a rapid and accurate means of identifying the site of origin of VT facilitating intraoperative mapping in patients undergoing surgical ablation.

Profound hypothermia for spinal cord protection in operations on the descending thoracic and thoracoabdominal aorta.

Elective hypothermic cardiopulmonary bypass with or without circulatory arrest has been used successfully for the treatment of complex aneurysms of the descending thoracic and thoracoabdominal aorta. Hypothermia has a protective effect on spinal cord function, and its use has been associated with a low incidence of paraplegia in traditionally high-risk patients. In our series, 96 consecutive patients underwent resection and graft replacement of diseased aortic segments of the distal aortic arch, the descending thoracic aorta, or the thoracoabdominal aorta. Thirty-day mortality was 7.3%, and the incidence of spinal cord ischemic injury was 3.4%. Our experience with hypothermic cardiopulmonary bypass and circulatory arrest confirms the safety and efficacy of the technique for operations on the descending thoracic and thoracoabdominal aorta.

Surgical management of the severely atherosclerotic ascending aorta during cardiac operations.

Severe atherosclerosis of the ascending aorta is associated with an increased incidence of stroke after cardiac surgery. Direct intraoperative epiaortic scanning is a rapid and accurate means for detection of ascending aortic atherosclerosis. When severe atheromatous disease is detected, graft replacement of the ascending aorta is our preferred method of management. During an 11-year period, 81 patients (mean age 71 years) who underwent coronary artery bypass were found to have severe ascending aortic atherosclerosis by epiaortic scanning. Using hypothermic circulatory arrest, 80 patients underwent partial (5) or complete (75) ascending aortic replacement. One patient underwent resection of a protruding aortic atheroma. In addition to partial or total replacement of the ascending aorta, 34 patients had replacement of the aortic arch, 19 had a valve replacement, and 6 had carotid endarterectomy. The 30-day mortality was 8.6% (7 patients). Four patients (4.9%) sustained perioperative strokes and 2 (2.5%) sustained transient perioperative ischemic neurological deficits. The 3-year survival rate was 40%. There was one stroke 4 months postoperatively that eventually led to late death. Elective resection and graft replacement of the severely atherosclerotic ascending aorta using hypothermic circulatory arrest in patients undergoing cardiac operations is a safe procedure, associated with an acceptable incidence of postoperative stroke. The procedure may provide long-term protection from subsequent embolic cerebral vascular events. However, long-term survival has been disappointing and is primarily related to generalized atherosclerosis.

Laparoscopic management of large retroperitoneal lymphoceles complicating aortic surgery.

Retroperitoneal lymphocele is a rare but debilitating complication of aortic replacement with synthetic graft. The only effective treatment reported to date is surgical reexploration and ligation of leaking lymphatics. This report illustrates the successful management of two patients with large retroperitoneal lymphoceles formed after aortic surgery using laparoscopic techniques. The available literature is reviewed. Laparoscopic fenestration of the lymphocele and laparoscopically assisted ligation of the leaking lymphatics combined with internal drainage resulted in long-term relief of compression symptoms, as observed, respectively, over the 5-year and 3-month follow-up periods. Percutaneous catheter drainage before laparoscopic management was unsuccessful in both cases. In addition, the unique presentation of a large retroperitoneal lymphocele with intestinal obstruction is reported, and currently available treatment options are discussed.

Impact of haplotypes of TNF in the natural course of infective endocarditis.

Based on previous findings for the role of single nucleotide polymorphisms (SNPs) of TNF for the predisposition for bloodstream infections, this study investigates the role of these SNPs at the promoter positions -376, -308, -238 in infective endocarditis (IE). In a case-control study, 83 patients with IE and 83 controls were enrolled. Blood genotyping for the presence of G or A alleles of the three SNPs was carried out using restriction fragment length polymorphisms. Haplotypes were calculated. Patients were mostly infected by Staphylococcus aureus (32.5%) and by species of enterococci (14.3%) and streptococci (14.3%). Carriage of the minor frequency A alleles at -238 of the promoter region of TNF was greater than in controls (8.4% versus 1.2%, p 0.003). The presence of any of the three GGA/GAA/AGA haplotypes was more frequent in patients with IE (OR 8.22, 95CI% 1.8-37.4, p 0.001). After multivariate logistic regression analysis, it was found that the only factor related to fatal outcome was carriage of the wild-type GGG haplotype (OR, 3.29, 95CI%, 1.05-10.29, p 0.04). GGA, AGA and GAA haplotypes were more frequent in patients with IE than in controls, suggesting a predisposition for IE and a potential protective role against fatal outcome, as the wild-type GGG haplotype was independently related with death.