Gianfederico Possati

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.

Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization.

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels--measured daily up to 72 hours before surgery, after surgery, and at discharge--showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 +/- 3.4 vs 1.4 +/- 0.9 days, p = 0.02) and in the hospital (6.7 +/- 4.0 vs 5.3 +/- 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization.

C-reactive protein is increased in patients with degenerative aortic valvular stenosis

OBJECTIVES The goal of this study was to assess the presence of systemic inflammation in degenerative aortic valvular stenosis. BACKGROUND Local inflammatory changes, resembling those observed in atherosclerosis, have been recently reported in degenerative aortic valvular stenosis. It is presently unknown whether systemic signs of inflammation, similar to those observed in atherosclerosis, may be present in this disorder. METHODS C-reactive protein (CRP) was measured by enzyme immunoassay in 141 subjects: 62 with trileaflet degenerative valvular aortic stenosis and 79 volunteers with similar demographic and clinical characteristics. IgG antibodies against Helicobacter pylori (enzyme-linked immunosorbant assay) and Chlamydia pneumoniae (microimmunofluorescence assay) were also measured. RESULTS C-reactive protein levels (mg/dl, mean +/- SD) were 0.848 +/- 1.42 in patients and 0.394 +/- 0.50 in controls (p = 0.0001, Mann-Whitney U test). Seroprevalence of H. pylori was 68.7% in patients and 79.7% in controls (p = NS), whereas seroprevalence of C. pneumoniae infection was higher in patients than it was in controls (59.7% vs. 33%, p = 0.003; chi-square test). After adjustment for various covariates in multiple logistic regression, the odds ratio for degenerative aortic stenosis was 3.41 for C. pneumoniae infection (95% confidence intervals [CI]: 1.60 to 7.30) and 2.76 for CRP (95% CI: 1.08 to 7.05). There was no significant difference in patients or controls in CRP levels according to the serostatus for C. pneumoniae. CONCLUSIONS Systemic signs of inflammation, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis. They do not seem to be linked to C. pneumoniae or H. pylori infection.

Elevated levels of C-reactive protein before coronary artery bypass grafting predict recurrence of ischemic events

C-reactive protein was measured in 86 patients undergoing coronary artery bypass graft surgery. Patients were followed up for 3.2 years (range 1 to 6). Patients with C-reactive protein > or = 3 mg/L had significantly increased risk of recurrent ischemia at 1 to 6 years after intervention.

Bypass versus drug-eluting stents at three years in SYNTAX patients with diabetes mellitus or metabolic syndrome.

BACKGROUND Diabetes mellitus increases adverse outcomes after coronary revascularization; however, the impact of metabolic syndrome is unclear. We examined the impact of diabetes and metabolic syndrome on coronary artery bypass graft surgery (CABG) and stenting outcomes to determine the optimal revascularization option for the treatment of complex coronary artery disease. METHODS Patients (n = 1,800) with left main or three-vessel disease or both were randomly allocated to treatment with a TAXUS Express(2) paclitaxel-eluting stent (PES) or CABG, and were included in predefined nondiabetic (n = 1,348) or diabetic subgroups (n = 452); 258 patients with diabetes also had metabolic syndrome. RESULTS Among diabetic patients, the 3-year major adverse cardiac and cerebrovascular event (MACCE) rate (22.9% CABG, 37.0% PES; p = 0.002) and revascularization rate (12.9% CABG, 28.0% PES; p < 0.001) were higher after PES treatment. Diabetes increased MACCE rates among PES-treated patients, but had little impact on results after CABG. Compared with CABG, PES treatment yielded comparable MACCE in diabetic patients (30.5% versus 29.8%, p =0.98) and nondiabetic patients (20.2% versus 20.3%, p =0.99) with low Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) study scores of 22 or less. For patients with SYNTAX Scores of 33 or greater, MACCE rates were lower with CABG (18.5% versus 45.9%, p < 0.001 diabetic; 19.8% versus 30.0%, p = 0.01 nondiabetic). Metabolic syndrome did not significantly predict MACCE or repeat revascularization. CONCLUSIONS These exploratory analyses suggest that among diabetic patients with complex left main or three-vessel disease, or both, 3-year MACCE is higher after PES compared with CABG. Although PES is a potential treatment option in patients with less complex lesions, CABG should be the revascularization option of choice for patients with more complex anatomic disease, especially with concurrent diabetes. Metabolic syndrome had little impact on 3-year outcomes.

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.