Mario Gaudino

The −174G/C Interleukin-6 Polymorphism Influences Postoperative Interleukin-6 Levels and Postoperative Atrial Fibrillation. Is Atrial Fibrillation an Inflammatory Complication?

Background—It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists. This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass (the −174 G/C polymorphism of the promoter of the Interleukin-6 gene) has a role in the pathogenesis of postoperative atrial fibrillation (AF). Patients and Results—In 110 primary isolated coronary artery bypass patients the −174G/C Interleukin-6 promoter gene variant was determined. Interleukin-6, fibrinogen and C-reactive protein plasma levels were determined preoperatively, 24, 48, and 72 hours after surgery and at discharge. Heart rate and rhythm were continuously monitored for the first 36 to 48 hours; daily 12-lead electrocardiograms were performed thereafter until discharge. GG, CT, and CC genotypes were found in 62, 38, and 10 patients, respectively. Multivariate analysis (which included genotype, age, sex, and classical risk factors for AF) identified the GG genotype as the only independent predictor of postoperative AF. The latter occurred in 33.9% of GG versus 10.4% of non-GG patients (hazard ratio 3.25, 95%CI 1.23 to 8.62). AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery (P <0.001 for difference between the area under the curve). Conclusion—The −174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF. These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication.

Long-Term Results of the Radial Artery Used for Myocardial Revascularization

Background—No information is available on the long-term results of radial artery (RA) grafts used as coronary artery bypass conduits. Methods and Results—In this report, we describe the long-term (105±9 months) angiographic results of a series of 90 consecutive patients in whom the RA was used as a coronary artery bypass conduit directly anastomosed to the ascending aorta. The long-term patency and perfect patency rates of the RA were 91.6% and 88%, respectively, versus 97.5% and 96.3% for internal thoracic artery grafts. The severity of stenosis of the target vessel clearly influenced long-term RA patency, whereas location of the target vessel and long-term use of calcium channel blockers did not influence angiographic results. Preserved endothelial function and absence of flow-limiting, fibrous, intimal hyperplasia were also documented. Conclusions—Ten years after surgery, RA grafts have excellent patency and perfect patency rates. Appropriate surgical technique and correct indication are the key factors for long-term RA patency.

Midterm clinical and angiographic results of radial artery grafts used for myocardial revascularization.

OBJECTIVE To evaluate the midterm angiographic results of the use of radial artery grafts for myocardial revascularization. METHODS The first 68 consecutive surviving patients who received a radial artery graft proximally anastomosed to the aorta at our institution were studied again at 5 years (mean 59 +/- 6.5 months) of follow-up; 48 of these patients had previously undergone an early angiographic examination. The response of the radial artery to the endovascular infusion of serotonin was evaluated 1 and 5 years after the operation, and the midterm status of the radial artery graft was correlated with the degree of preoperative stenosis of the target vessel and with calcium-channel blocker therapy. RESULTS The patency and perfect patency rates of the radial artery grafts 5 years after the operation were 91.9% and 87.0%, respectively. All radial artery grafts that were patent early after the operation remained patent at midterm follow-up, and early parietal irregularities in 7 patients were seen to have disappeared after 5 years. The early propensity toward graft spasm after serotonin challenge was markedly decreased at midterm follow-up. The continued use of calcium-channel antagonists after the first postoperative year did not influence the radial artery graft status, whereas the preoperative severity of the target-vessel stenosis markedly influenced the angiographic results. CONCLUSIONS The midterm angiographic results of radial artery grafts used for myocardial revascularization are excellent. The correct surgical indication is essential. Continued therapy with calcium-channel antagonists after the first year does not influence the midterm angiographic results.

Postoperative Inflammatory Reaction and Atrial Fibrillation: Simple Correlation or Causation?

Atrial fibrillation after cardiac operations is a source of morbidity and resource consumption. This systematic review of literature analyzes the current evidence on its pathophysiologic link with the systemic inflammatory response elicited by surgery and cardiopulmonary bypass. Meta-analysis of randomized studies on the effect of off-pump surgery or statin pre-treatment on the incidence of atrial fibrillation was performed. The concept of inflammation as a pathophysiologic determinant of postoperative atrial fibrillation is supported by the literature. The modulation of post-cardiopulmonary bypass systemic inflammation will probably represent a major therapeutic goal in the prevention of postoperative atrial fibrillation. Statins seem to be the most promising pharmacological strategy.

Genetic control of postoperative systemic inflammatory reaction and pulmonary and renal complications after coronary artery surgery.

BACKGROUND Although some data suggest that the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction may influence postoperative morbidity, this hypothesis has not been clinically tested to date. Methods and results The -174 G/C polymorphism of the promoter of the interleukin 6 gene was determined preoperatively in 111 consecutive patients submitted to primary isolated coronary artery bypass. The results of the genetic analysis were then correlated with the postoperative interleukin 6 levels and the development of postoperative renal and pulmonary complications. G homozygotes had significantly higher interleukin 6 levels postoperatively (P <.0001 for the difference between areas under the curve). These patients also had worse postoperative pulmonary and renal function. The mean perioperative difference in serum creatinine, potassium, and nitrogen was 0.82 +/- 0.34, 0.99 +/- 0.44, and 10.1 +/- 7.8 mg/dL versus 0.18 +/- 0.14, 0.15 +/- 0.48, and 2.6 +/- 4.1 mg/dL for GG versus non-GG carriers (P <.0001), respectively. The mean respiratory index at 6 and 12 hours was 2.9 +/- 0.8 and 2.8 +/- 0.3 versus 2.1 +/- 0.5 and 1.3 +/- 0.1, respectively (P <.0001). The mean duration of mechanical ventilation was 22.5 +/- 2.1 versus 12.7 +/- 6.7 hours (P <.01). A correlation was found between postoperative interleukin 6 levels and renal and pulmonary complications. CONCLUSION The interleukin 6 -174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.

Risks of Using Internal Thoracic Artery Grafts in Patients in Chronic Hemodialysis via Upper Extremity Arteriovenous Fistula

Background—In patients in chronic hemodialysis via upper extremity arteriovenous fistula in whom ipsilateral internal thoracic artery graft was used for myocardial revascularization, hemodynamic interference between the fistula and the graft during dialysis can be hypothesized. Methods and Results—In 5 patients undergoing chronic hemodialysis via upper extremity arteriovenous fistula, ipsilateral to an internal thoracic to left anterior descending graft mammary flow was studied by means of transthoracic echo-color Doppler at baseline and during hemodialysis. Flow in the contralateral mammary artery was used as control. Transthoracic echocardiography was performed in concomitance with flow evaluation to assess eventual modifications of left ventricular segmental wall motion. Immediately after hemodialysis pump start there was a marked reduction of peak systolic and end-diastolic velocities and time average mean velocity and flow in the ITA ipsilateral to the fistula, whereas no substantial hemodynamic modification was evident in the contralateral artery. Dialysis-induced reduction of ipsilateral ITA flow was accompanied by evidence of hypokinesia of the anterior left ventricular wall. Three cases also experienced clinical angina. Conclusions—Hemodynamically evident flow steal and consequent myocardial ischemia develop during hemodialysis in patients with upper extremity arteriovenous fistula and ipsilateral internal thoracic artery to coronary graft. These data have major implications for patients’ management, both for nephrologists and cardiac surgeons.

Hemodynamic and functional consequences of radial artery removal for coronary artery bypass grafting.

Five years after surgery the echo-Doppler characteristics of the forearm circulation and the transcutaneous oxygen and carbon dioxide pressures of the operated and control arm were determined at rest and under conditions of hand exercise in 34 patients who received a radial artery graft for myocardial revascularization. Doppler measurements showed the ulnar compensation to radial artery removal, and transcutaneous measurements demonstrated a moderate degree of exercise-induced hand ischemia on the operated site.

Preoperative C-reactive protein level and outcome following coronary surgery

OBJECTIVE It has been suggested that a preoperative level of C-reactive protein (CRP)>5mg/l is predictive of postoperative complications in cardiac surgery patients. MATERIAL AND METHODS Among 113 primary isolated coronary artery bypass patients, CRP was determined preoperatively and fibrinogen, interleukine 6, plasminogen activator inhibitor-1, prothrombin time, activated partial thromboplastin time, platelets and white blood cells count measured before surgery, 24, 48 and 72h thereafter and at hospital discharge. The clinical course of all cases was prospectively recorded. Data were then analysed according to the preoperative CRP level by dividing the patients into two groups (CRP>5mg/l or CRP<5mg/l). RESULTS The in-hospital results were similar between the two patients groups. Even the postoperative haematic inflammatory markers did not significantly differ according to the preoperative CRP level. CONCLUSION In this prospective study, a preoperative level of CRP>5mg/l did not predict in-hospital postoperative complications nor influence the extent of the inflammatory activation in primary isolated coronary bypass patients.

Arterial Versus Venous Bypass Grafts in Patients With In-Stent Restenosis

Background—In patients who develop in-stent restenosis, successful revascularization can be difficult to achieve using percutaneous methods. This study was designed to verify the surgical results in this setting and to evaluate the potential beneficial role of arterial bypass conduits. Methods and Results—Sixty consecutive coronary artery bypass patients with previous in-stent restenosis and 60 control cases were randomly assigned to receive an arterial conduit (either right internal thoracic or radial artery; study group) or a great saphenous vein graft (control group) on the first obtuse marginal artery to complete the surgical revascularization procedure. At a mean follow-up of 52±11 months, patients were reassessed clinically and by angiography. Freedom from clinical and instrumental evidence of ischemia recurrence was found in 19 of 60 subjects in the study group versus 45 of 60 in the control series (P=0.01). The results of the arterial grafts were excellent in both the study and control groups (right internal thoracic artery patency rate, 19 of 20 for both, and radial artery patency rate, 20 of 20 versus 19 of 20; P=0.99). Saphenous vein grafts showed lower patency rate than arterial grafts in both series and had extremely high failure rate in the study group (patency rate, 10 of 20 in the study group versus 18 of 20 in the control group; P=0.001). Use of venous graft was an independent predictor of failure in the study group, whereas hypercholesterolemia was associated with graft failure in both series. Conclusions—Venous grafts have an high incidence of failure among cases who previously developed in-stent restenosis, whereas the use of arterial conduits can improve the angiographic and clinical results. Arterial grafts should probably be the first surgical choice in this patient population.

Coronary artery bypass grafting in type II diabetic patients: a comparison between insulin-dependent and non-insulin-dependent patients at short- and mid-term follow-up

BACKGROUND Diabetes is a well-established risk factor for coronary artery disease, and it is associated with an increased rate of early and late adverse events after myocardial revascularization by coronary artery bypass grafting. METHODS A prospective follow-up study was done to evaluate the short-term and mid-term outcomes of type II diabetic patients who had coronary artery bypass grafting at our institution between 1996 and May 1999. A total of 200 patients, 100 insulin-dependent diabetic patients (group I) and 100 non-insulin-dependent diabetic patients (group II), met the inclusion criteria of the study and were included in the clinical follow-up study. RESULTS The characteristics of the patients of the two groups were similar for baseline clinical angiographic and operative characteristics. In particular, no significant differences in cardiopulmonary bypass and aortic cross-clamping times were noted between the two groups. The number grafts per patient was similar between the two groups. There were no in-hospital deaths, but postoperative complications were different among the two series. In fact, 33% of patients in group I had at least one major complication compared with 20% in group II (p = 0.037). The cumulative number of complications was 148 in group I and 69 in group II, and the mean number of complications per patient was 4.5 and 3.5 in groups I and II, respectively. The major differences in perioperative complication rates were found in the need for prolonged (> 24 hours) ventilation, occurrence of respiratory or renal insufficiency, and mediastinitis. The mean length of stay in the intensive care unit and for total hospitalization were longer in group I than group II (4.3 +/- 2.8 days versus 2.8 +/- 2.7 days [p = 0.010] and 11.1 +/- 2.2 days versus 7.2 +/- 2.4 group II [p < 0.05], respectively). At long-term follow-up, group I patients had a significantly higher mortality rate (29% versus 10%, p < 0.001). Moreover, overall late cardiac and noncardiac complication rates were significantly higher in group I than II (37% versus 22%, p = 0.02). In the multivariate analysis including several preoperative and operative variables, treatment by insulin, advanced age (> 75 years), left ventricular dysfunction (left ventricular ejection fraction < 35%), and complex lesions at coronary angiography (American Heart Association lesion classification type C lesion) were found as independent predictors of increased mortality. CONCLUSIONS Our data show that patients with insulin-dependent type II diabetes who had coronary artery bypass grafting have a significantly higher rate of major postoperative complications with an extremely unfavorable short- and long-term prognosis. Diabetic patients on insulin treatment should be considered high-risk candidates for coronary artery bypass grafting and require intense perioperative and long-term monitoring. Further studies will be necessary to investigate whether such conclusions may be appropriate for newer surgical strategies such as off-pump operation.