Amir Kramer

Anti–Tumor Necrosis Factor-Alpha Improves Myocardial Recovery After Ischemia and Reperfusion ☆

OBJECTIVES This study sought to assess the importance of locally released or paracrine myocardial tumor necrosis factor-alpha (TNF-alpha) in the evolution of postischemic myocardial dysfunction and to use immunohistochemical studies to localize TNF-alpha within the myocardium. BACKGROUND TNF-alpha is implicated as a systemic mediator in the development of myocardial ischemia-reperfusion injury by promoting leukocyte myocardial infiltration, and it has been shown to originate from noncardiac peripheral mononuclear cells. We have recently documented in a blood-free environment the release of TNF-alpha from the ischemic-reperfused myocardium. METHODS Isolated rat hearts undergoing 1 h of global cardioplegia-induced ischemia and 30 min of reperfusion were investigated with use of the modified Langendorff model. Hearts were randomly divided into three subgroups: group A, control group; and groups B and C, isolated hearts receiving cardioplegic solution containing monoclonal hamster antimurine TNF-alpha antibodies (group B) or hamster IgG (group C). RESULTS Significant amounts of TNF-alpha were detected in group A and group C effluent on 1 min of reperfusion (752 +/- 212 and 958 +/- 409 pmol/ml, respectively). However, in group B, TNF-alpha was below detectable levels. In this group, postischemic left ventricular peak systolic pressures, first derivative of the rise in left ventricular pressure (dP/dtmax), pressure-time integral, coronary flow and O2 consumption improved (analysis of variance [ANOVA] p < 0.0001 for all variables) compared with values in groups A and C; creatine kinase levels decreased (p < 0.005); and myocardial structure was preserved. Immunohistochemical staining localized TNF-alpha to cardiac myocytes and to endothelial cells. CONCLUSIONS Anti-TNF-alpha neutralizes local TNF-alpha release from cardiac myocytes after ischemia and improves myocardial recovery during reperfusion, indicating that postischemic paracrine TNF-alpha release plays an active role in myocardial dysfunction.

Low-molecular-weight heparin for prosthetic heart valves: treatment failure

There is no adequate substitute therapy for patients with prosthetic heart valves, in whom anticoagulation with warfarin or unfractionated heparin must be withheld. In the literature there are several reports describing successful treatment with low-molecular-weight heparin in patients with prosthetic heart valves. We report two cases of low-molecular-weight heparin treatment failure resulting in thrombosed prosthetic heart valves with stormy clinical presentations, who underwent successful valve replacements.

Sternal wound infections in patients after coronary artery bypass grafting using bilateral skeletonized internal mammary arteries.

OBJECTIVES This study evaluated the risks of sternal wound infections in patients undergoing myocardial revascularization using bilateral skeletonized internal mammary arteries (IMAs). BACKGROUND The skeletonized IMA is longer than the pedicled one, thus providing the cardiac surgeon with increased versatility for arterial myocardial revascularization without the use of vein grafts. It is isolated from the chest wall gently with scissors and silver clips, and no cauterization is employed. Preservation of collateral blood supply to the sternum and avoidance of thermal injury enable more rapid healing and decrease the risk of sternal wound infection. METHODS From April 1996 to August 1997, 545 patients underwent arterial myocardial revascularization using bilateral skeletonized IMAs. The right gastroepiploic artery was used in 100 patients (18%). The average age of the patients was 65 years; 431 (79%) were men and 114 (21%) were women; 179 (33%) were older than 70 years of age; 166 (30%) were diabetics. The average number of grafts was 3.2 per patient. RESULTS The 30-day operative mortality rate was 2% (n = 11). There were six perioperative infarcts (1.1%) and six strokes (1.1%); 9 patients had sternal infection (1.7%) and 15 (2.8%) had superficial infection. Risk factors for sternal infection were chronic obstructive pulmonary disease and emergency operation. Superficial sternal wound infections were more common in women and in patients with chronic obstructive pulmonary disease, renal failure, or peripheral vascular disease. The 1-year actuarial survival rate was 97%. Two of the six late deaths were not cardiac-related. Late dehiscence occurred in three patients (0.6%). The death rate (early and late) of patients with any sternal complication was higher than that of patients without those complications (33% vs. 2.7%). CONCLUSIONS Routine arterial myocardial revascularization using bilateral skeletonized IMAs is safe, and postoperative morbidity and mortality rates are low, even in elderly patients and those with diabetes. Chronic obstructive pulmonary disease and emergency operations were found to be associated with an increased risk of sternal infections, and the authors recommend avoiding the use of bilateral skeletonized IMAs in patients with these preoperative risk factors.

Bilateral internal thoracic artery grafting : midterm results of composite versus in situ crossover graft

BACKGROUND Two common techniques of bilateral internal thoracic artery grafting are the composite T graft and in situ crossover graft. The superiority of one method over the other has not yet been established. METHODS From April 1996 to July 1999, bilateral skeletonized internal thoracic arteries were used as T grafts (composite group, n = 649) and in situ grafts (cross group, n = 351) in 1,000 consecutive patients. In the cross group, in situ right internal thoracic artery was routed anterior to the aorta across the midline for grafting to the left anterior descending artery, and the left internal thoracic artery was used for the circumflex branches. RESULTS The two groups had comparable preoperative risk profiles. Bypass time and aortic cross-clamping time were longer in the composite group (80 +/- 38 and 67 +/- 29 minutes versus 66 +/- 43 and 55 +/- 34 minutes, respectively). Number of anastomoses per patient was similar (3.1 versus 3.2). However, more sequential anastomoses were performed in the composite group (62% versus 53%), and the gastroepiploic artery was used more often in the cross group (30% versus 19%). Thirty-day mortality was 3.9% in the composite and 2.3% in the cross group (not significant). Occurrence of postoperative complications (sternal infection, myocardial infarction, cerebrovascular accident, and bleeding) was similar. Late follow-up (2 to 56 months) showed increased return of angina (6% versus 3.1%; p = 0.046) and decreased 4-year survival (Kaplan-Meier; 86% +/- 2.7% versus 92.4% +/- 1.5%; p = 0.07) in composite patients. CONCLUSIONS Early results of bilateral internal thoracic artery grafting with composite T graft are comparable with those of in situ grafts. However, increased angina return and decreased midterm survival led us to recommend in situ grafting whenever technically possible.

Influence of bilateral skeletonized harvesting on occurrence of deep sternal wound infection in 1,000 consecutive patients undergoing bilateral internal thoracic artery grafting.

ObjectiveTo evaluate the risk of deep sternal infection in a large patient cohort following bilateral internal thoracic artery (BITA) grafting using skeletonized BITA dissection. Summary Background DataComplete myocardial revascularization using BITAs improves long-term survival and lowers the rate of repeat operations. Harvesting of ITAs as skeletonized vessels preserves sternal collateral blood supply, thus enabling rapid sternal healing with less risk of deep sternal infection. MethodsOne thousand consecutive patients (763 men, 340 patients >70 years old, 304 diabetics) underwent skeletonized BITA grafting from April 1996 to July 1999. ResultsThe 30-day mortality rate was 3.4%. There were 10 perioperative infarcts, 16 strokes, and 22 deep sternal infections. There was an increased risk of deep sternal infection in repeat coronary artery bypass grafting (CABG) operations (15%), chronic obstructive pulmonary disease (COPD) (6.2%), congestive heart failure (4.7%), left ventricular dysfunction (ejection fraction < 35%, 4.5%), and longer aortic cross-clamping time. After adjustment for other demographic, clinical, and surgical predictors, the only independent predictors of deep sternal infection were repeat operations, COPD, and duration of aortic cross-clamping. No patients in the reoperation subgroup died, but three of six COPD patients with deep sternal infection died, and COPD was an independent predictor of overall (early + late) mortality. ConclusionsSkeletonized BITA grafting carries an acceptable risk of deep sternal infection but is not recommended for repeat CABG or for patients with COPD.

Technical aspects of double-skeletonized internal mammary artery grafting

BACKGROUND Bilateral internal mammary artery (IMA) grafting is performed to provide complete arterial myocardial revascularization with the intention of decreasing postoperative return of angina and the need for reoperation. We present here technical views of double-skeletonized IMA grafting, and evaluate its clinical outcome. METHODS Skeletonized IMA is harvested gently with scissors and silver clips, without use of cauterization, and embedded in a small syringe filled with papaverine. Three strategies for arterial revascularization were employed in 762 consecutive patients: (1) the cross arrangement (242 patients, 32%), where the in situ right internal mammary artery (RIMA) is used for the left anterior descending artery (LAD), in situ left internal mammary artery (LIMA) to circumflex marginal branches and the gastroepiploic artery for the right coronary artery (RCA); (2) the composite arrangement (476 patients, 62%), where free IMA is attached end-to-side to the other in situ IMA; and (3) the natural arrangement (44 patients, 6%), where the in situ RIMA is connected to the RCA and in situ LIMA to LAD. Mean age was 66 years (range 30 to 92). Two hundred ninety-two patients (38%) were older than 70, and 229 (30%) were diabetic. RESULTS Operative mortality was 2.5% (n = 19). The mortality of urgent and elective cases was 1.2% (8 of 663), and that of emergency operation was 11% (11 of 99). There were 9 (1.2%) perioperative myocardial infarctions, and 10 patients (1.3%) sustained strokes. Sternal wound infection occurred in 14 (1.8%). CONCLUSIONS The three strategies described here provide the surgeon with the versatility required for arterial revascularization with bilateral IMAs in most patients referred for coronary artery bypass grafting.

Emergency myocardial revascularization for acute myocardial infarction: survival benefits of avoiding cardiopulmonary bypass

OBJECTIVE Emergency coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI) is associated with increased operative mortality. It has been suggested that this mortality might be reduced by performing the operation without cardiopulmonary bypass (CPB). METHODS Between January 1992 and April 1998, 77 patients underwent emergency CABG within 48 h of AMI. Thirty seven were operated on with CPB, and 40 without CPB. The two groups were similar regarding age, gender, left-ventricular ejection fraction (EF) and preoperative use of intra-aortic balloon pump (IABP; 50%). The mean number of grafts/patient was 3 in the CPB group, and 1.9 in the No-CPB group (P<0.0001). RESULTS Operative mortality in the CPB group was 24% (nine of 37) compared to 5% (two of 40) without CPB (P=0.015). Follow-up ranged between 6 and 66 months. There were no late deaths in the CPB group compared to nine (22%) in the No-CPB group (P<0.0066). Patients operated on with CPB had lower rates of recurrent angina (0 versus 15%; P=0.04) and re-interventions (0 versus 15%; P=0.04). CONCLUSIONS Our experience suggests that CABG without CPB is the preferred method of myocardial revascularization, due to the fact that it carries lower mortality than CABG with CPB. The trade-off includes increased rates of recurrent angina, re-interventions and late mortality.

Routine Use of Bilateral Skeletonized Internal Thoracic Artery Grafting Long-Term Results

Background— Skeletonized harvesting of the internal thoracic artery (ITA) decreases the severity of sternal devascularization, thus reducing the risk of postoperative sternal complications in patients undergoing bilateral ITA grafting. Methods and Results— Between 1996 and 2001, 1515 consecutive patients underwent skeletonized bilateral ITA grafting. Of the 1179 male and 336 female patients, 641 (42.3%) were >70 years of age, and 519 (34.2%) had diabetes mellitus. Operative mortality was 2.8%. Early postoperative morbidity included sternal infection (1.6%), cerebrovascular accident (3%), and perioperative myocardial infarction (1%). Multiple regression analysis showed chronic obstructive pulmonary disease (odds ratio, 11.3; 95% confidence interval [CI], 4.45 to 28.55), repeat operation (odds ratio, 12.7; 95% CI, 3.25 to 49.56), and diabetes mellitus (non–insulin dependent: odds ratio, 4.64; 95% CI, 1.85 to 11.59; insulin dependent: odds ratio, 6.9; 95% CI, 1.35 to 35.27) to be associated with increased risk of sternal infection. Follow-up (between 5 and 12 years) revealed 305 late deaths. Kaplan-Meier 10-year survival rates for patients <65, 65 to 74, and >75 years of age were 87%, 75%, and 52%, respectively. Cox regression analysis revealed increased overall mortality (early and late) in patients with peripheral vascular disease (hazard ratio [HR], 1.8; 95% CI, 1.39 to 2.33), patients >75 years of age (HR, 7.23; 95% CI, 4.16 to 12.55), those undergoing repeat operations (HR, 2.22; 95% CI, 1.27 to 3.89), patients with preoperative congestive heart failure (HR, 1.64; 95% CI, 1.29 to 3.75), and those with chronic renal failure (HR, 1.52; 95% CI, 1.11 to 2.01). Operations performed without cardiopulmonary bypass were associated with better postoperative survival (HR, 0.66; 95% CI, 0.49 to 0.87). Conclusions— Bilateral ITA grafting is associated with low morbidity and good long-term results. Use of skeletonized bilateral ITA is appropriate for the elderly and most patients with diabetes; however, it is not recommended for repeat operations or for patients with chronic obstructive pulmonary disease.

Arterial myocardial revascularization with in situ crossover right internal thoracic artery to left anterior descending artery.

BACKGROUND The extra length obtained by skeletonizing the internal thoracic arteries (ITAs) enables versatile use of in situ bilateral ITAs for coronary artery bypass grafting, as the longer skeletonized right ITA more easily reaches the anastomotic site on the left anterior descending coronary artery. METHODS Between April 1996 and November 1999, 365 consecutive patients underwent revascularization with bilateral in situ ITAs (29% of 1,250 grafting procedures performed with both ITAs in our department during this period). The right ITA was routed anterior to the aorta to graft the left anterior descending coronary artery, and the in situ left ITA was used to graft circumflex branches. Right coronary artery branches were grafted with right gastroepiploic artery or saphenous vein graft. The right ITA crossed the midline above the aorta at the most cranial point to avoid damage in case of a repeat sternotomy in the future. RESULTS The operative mortality rate was 2.2% (8 patients). Postoperative morbidity included seven strokes (1.9%), eight sternal wound infections (2.2%), and four perioperative myocardial infarctions (1.1%). Follow-up (6 to 49 months) of 97% of hospital survivors showed a return of angina in 3%. Postoperative coronary angiography (22 patients) revealed a 95% patency rate of both ITAs. One-year and 4-year survival rates (Kaplan-Meier) were 95% and 92.4%, respectively. Important predictors of an early unfavorable event were chronic obstructive pulmonary disease, old age (> or = 70 years), emergency operation, and diabetes. Chronic obstructive pulmonary disease was the only independent predictor of sternal wound infection (odds ratio, 15; 95% confidence interval, 2.8 to 80). It also predicted decreased late survival (hazard ratio, 8.3; 95% confidence interval, 3 to 21.5). CONCLUSIONS With skeletonized dissection of ITAs, the right ITA easily reaches the left anterior descending coronary artery for left-sided arterial revascularization with in situ bilateral ITAs. This procedure is safe, but we recommend avoiding its use in patients with chronic obstructive pulmonary disease.

Routine use of bilateral skeletonized internal mammary arteries for myocardial revascularization

BACKGROUND Complete arterial myocardial revascularization without the use of saphenous veins grafts was primarily performed on selected patient populations such as the young and nondiabetic. In a recently developed surgical technique, the internal mammary artery is dissected gently as a longer skeletonized artery, providing greater versatility for complete arterial revascularization, without saphenous veins grafts. METHODS We prospectively evaluated the impact of the routine use of double skeletonized internal mammary artery in 472 patients who underwent coronary artery bypass grafting between April 1996 and June 1997. Their average age was 65 years (30 to 87 years), 383 (83%) were men, and 89 (17%) women. One hundred sixty-nine (36%) of the patients were older than 70 years, and 145 (31%) were diabetic. The average number of grafts was 3.2 per patient (two to six grafts). RESULTS Operative mortality was 1.7% (n = 8). The mortality of urgent and elective patients was 0.7% (3 of 410 patients), and that of emergency operations was 8.1% (5 of 62 patients; p < 0.01). There were three (0.6%) perioperative infarcts, and 6 patients (1.3%) sustained strokes. Sternal wound infection occurred in 8 patients (1.7%). Postoperative follow-up (1 to 25 months) was available in 462 patients (99%). Two-year actuarial survival was 96.8%, and 92% of the surviving patients are well and free of angina. Neither diabetes mellitus nor old age (>70 years) were significant independent predictors of any early or late untoward events. None of the 70 diabetic patients more than 65 years of age developed sternal wound infection. Chronic lung disease was found to be the only independent predictor for sternal infections. CONCLUSIONS Routine use of bilateral skeletonized internal mammary artery is a safe replacement for the current myocardial revascularization technique even in the old and diabetic patients.