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Enhanced platelet reactivity may play a role in cardiac allograft vasculopathy (CAV) progression. The use of antiplatelet agents after heart transplantation (HT) has been inconsistent and although aspirin (ASA) is often a part of the medication regimen after HT, limited evidence is available on its benefit.CAV progression was assessed by measuring the difference in plaque volume and plaque index between the last follow-up and the baseline coronary intravascular ultrasound examination. Overall, 529 HT recipients were retrospectively analyzed (337 had ≥2 intravascular ultrasound studies). The progression in plaque volume (P = .007) and plaque index (P = .002) was significantly attenuated among patients treated with early ASA (within the first year after HT). Over a 6.7-year follow-up, all-cause mortality was lower with early ASA compared with late or no ASA use (P.001). No cardiac deaths were observed in the early ASA group, and the risk of CAV-related graft dysfunction was significantly lower in this group (P = .03). However, the composite of all CAV-related events (cardiac death, CAV-related graft dysfunction, or coronary angioplasty) was not significantly different between the groups (P = .16).Early ASA use after HT may delay CAV progression and decrease mortality and CAV-related graft dysfunction, but does not seem to affect overall CAV-associated events.

OBJECTIVES Our goal was to compare the rates of in-hospital and 30-day major adverse cardiac and cerebrovascular events (MACCE) including death, stroke, myocardial infarction and repeat revascularization in patients with multivessel disease undergoing multiarterial (MultArt) coronary artery bypass grafting (CABG) with the left internal mammary artery/saphenous vein (LIMA/SV) CABG or percutaneous coronary intervention (PCI). METHODS From 1 January 1993 to 31 December 2009, 12 615 consecutive patients underwent isolated primary CABG (n = 6667) with LIMA/SV (n = 5712) or MultArt (n = 955) or were treated by PCI (n = 5948) with balloon angioplasty (n = 1020), bare metal stent (n = 3242), and drug-eluting stent (n = 1686). We excluded patients with acute myocardial infarction. We matched the CABG group with the 3 PCI subgroups, and the PCI group with the 2 CABG subgroups. Multivariable analyses were used to evaluate the impact of CABG versus PCI and their subgroups on early MACCE. RESULTS Unadjusted early MACCE were lower for MultArt (1.5%) than for LIMA/SV (4.5%, P

To assess long-term survival with repeat coronary artery bypass grafting (RCABG) or percutaneous coronary intervention (PCI) in patients with previous CABG.From January 1, 2000, through December 31, 2013, 1612 Mayo Clinic patients underwent RCABG (n=215) or PCI (n=1397) after previous CABG. The RCABG cohort was grouped by use of saphenous vein grafts only (n=75), or with additional arterial grafts (n=140); the PCI cohort by, bare metal stents (BMS; n=628), or drug-eluting stents (DES; n=769), and by the treated target into native coronary artery (n=943), bypass grafts only (n=338), or both (n=116). Multivariable regression and propensity score analysis (n=280 matched patients) were used.In multivariable analysis, the 30-day mortality was increased in RCABG versus PCI patients (hazard ratio [HR], 5.32; 95%CI, 2.34-12.08; P.001), but overall survival after 30 days improved with RCABG (HR, 0.72; 95% CI, 0.55-0.94; P=.01). Internal mammary arteries were used in 61% (129 of 215) of previous CABG patients and improved survival (HR, 0.82; 95% CI, 0.69-0.98; P=.03). Patients treated with drug-eluting stent had better 10-year survival (HR, 0.74; 95% CI, 0.59-0.91; P=.001) than those with bare metal stent alone. In matched patients, RCABG had improved late survival over PCI: 48% vs 33% (HR, 0.57; 95% CI, 0.35-0.91; P=.02). Compared with RCABG, patients with PCI involving bypass grafts (n=60) had increased late mortality (HR, 1.62; 95% CI, 1.10-2.37; P=.01), whereas those having PCI of native coronary arteries (n=80) did not (HR, 1.09; 95% CI, 0.75-1.59; P=.65).RCABG is associated with improved long-term survival after previous CABG, especially compared with PCI involving bypass grafts.

We sought to identify the trends in bilateral internal thoracic artery use and determine the degree to which the survival advantage of bilateral internal thoracic artery revascularization persists among perceived "high-risk" patients, compared with the use of left internal thoracic artery alone.A retrospective review was conducted of patients who underwent isolated coronary artery bypass grafting for multivessel coronary artery disease at the Mayo Clinic between January 2000 and December 2015. Propensity score matching was performed between patients with bilateral internal thoracic artery and left internal thoracic artery alone grafts (1011 matched pairs). Effect of bilateral internal thoracic artery use on survival in "high-risk" patients (ejection fraction40%, body mass index ≥30, age ≥70 years, diabetes, chronic lung disease, cerebrovascular accident) was evaluated.A total of 6468 isolated coronary artery bypass grafts were performed (5431 using left internal thoracic artery alone, 1037 using bilateral internal thoracic artery). There was an increasing trend in bilateral internal thoracic artery use (P value for linear trend = .005), with the percentage of coronary artery bypass grafting cases with bilateral internal thoracic artery doubling over the last 4 years (13% in 2012 to 27% in 2015). Propensity-matched comparisons showed a survival advantage for bilateral internal thoracic artery (hazard ratio, 0.81; 95% confidence interval, 0.66-0.99; P = .043). Risk of deep sternal wound infection, although higher in the bilateral internal thoracic artery group, was not significant (1.2% vs 0.5%; P = .088). None of the "high-risk" subsets of patients showed an adverse effect of bilateral internal thoracic artery on survival.Bilateral internal thoracic artery use in coronary artery bypass grafting is increasing over time. There is a consistent survival benefit with bilateral internal thoracic artery use, extending to patients with higher-risk comorbidities, suggesting the need for further expansion in use of this technique.

PCSK9-i are gaining traction as effective lipid-lowering agents. We hypothesized that female patients were under-represented in landmark clinical trials of PCSK9-i. In this meta-analysis, we searched and reviewed all currently available randomized clinical trials (RCTs) of PCSK9-i. We defined the

Identifying the cardiotoxic potential of new anti-cancer drugs is essential in order to balance efficacy and toxicity. We performed Pubmed search of 4 chemotherapy drugs and ‘cardiotoxicity’. Of these 4 drugs, 2 have a known association with cardiac toxicity. We created plots representing the

Background Coronary artery bypass graft surgery is superior to percutaneous intervention in diabetic patients with multivessel disease. The use of bilateral internal thoracic arteries (BITA) may provide better long-term graft patency, but the risk of postoperative deep sternal wound infection has limited its use in diabetic patients. However, studies have reported conflicting results, and require systematic evaluation. Methods MEDLINE, EMBASE, World of Science, and the Cochrane library were searched for randomized controlled trials and observational studies comparing the incidence of deep sternal wound infection in diabetic patients undergoing either left internal thoracic artery (LITA) or BITA harvest. We used random effect models to compare risk ratios within groups. Results One randomized controlled trial and 10 observational studies (126,235 diabetic patients: 122,465 LITA, 3,770 BITA) met inclusion criteria. Deep sternal wound infection occurred in 3.1% and 1.6% for the BITA and LITA cohorts, respectively. The risk ratio for deep sternal wound infection development was 1.71 (1.37 to 2.14) for BITA compared with LITA. Patients who underwent skeletonized BITA harvest had a similar risk of deep sternal wound infection compared with LITA (0.9 [0.42 to 2.09]), although pedicled harvest demonstrated increased risk (1.77 [1.4 to 2.23]). Early mortality was comparable in the LITA cohort (2.5%) and the BITA cohort (2.3%; p = 0.8). Conclusions The risk of deep sternal wound infection can be minimized in diabetic patients undergoing coronary artery bypass graft surgery by performing ITA harvested in a skeletonized manner with meticulous attention to preserving sternal blood flow. Pedicled harvest is to be discouraged when utilizing both ITA owing to a significant increase in the risk of postoperative deep sternal wound infection.

Background The study compared downstream coronary and conduit disease progression in the left anterior descending coronary artery treated with coronary artery bypass grafting using the left internal mammary artery ( LIMA ) versus percutaneous coronary intervention with bare metal stent ( BMS ) or drug eluting stent ( DES ). Methods and Results A total of 12 301 consecutive patients underwent isolated primary coronary revascularization, of which 2386 met our inclusion criteria (Percutaneous coronary intervention, n=1450; coronary artery bypass grafting, n=936). Propensity score analysis matched 628 patients, of which 468 were treated to the left anterior descending with coronary artery bypass grafting with LIMA (n=314), percutaneous coronary intervention with BMS (n=94), and DES (n=60). Coronary angiograms were analyzed by quantitative coronary angiography ( QCA ; n=433). Cumulative downstream coronary and conduit disease progression were estimated by Kaplan–Meier method and effect of treatment type by Cox proportional hazard models. Patients treated with LIMA had significantly lower risk of downstream coronary disease progression at follow‐up angiogram compared with BMS and DES (hazard ratio [ HR ] [95% CI ], 0.34; [0.20–0.59]; P =0.0002; and HR [95% CI ], 0.39; [0.20–0.79]; P =0.01, respectively). LIMA was associated with a lower risk of conduit disease progression compared to BMS and DES ( HR [95% CI ], 0.18; [0.12–0.28]; P HR [95% CI ], 0.27; [0.16–0.46]; P BMS was associated with higher HR for downstream coronary and conduit disease progression compared with DES , but the difference did not reach statistical significance ( HR [95% CI], 1.13; [0.57–2.36]; P =0.73; and HR [95% CI ], 1.46; [0.88–2.50]; P =0.14, respectively). Conclusions LIMA grafting to left anterior descending is associated with significantly lower risk of downstream coronary and conduit disease progression compared to percutaneous coronary intervention with BMS and DES .

Diabetes mellitus is a risk factor for late death in patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Whether extending multiple arterial grafts (MA) to diabetic patients improves survival compared with conventional left internal mammary artery

This study compares the outcome of percutaneous coronary interventions (PCI) with bilateral internal thoracic grafting (BITA) in diabetic patients.From May 1996 to December 1999, 802 consecutive diabetic patients underwent myocardial revascularization: 363 by PCI and 439 by BITA. The two groups were similar; however, left main disease (28% versus 3.3%), ejection fraction less than 0.35 (14.5% versus 5.5%), and chronic obstructive lung disease (8.4% versus 3%) were more prevalent in the BITA group, and prior percutaneous transluminal coronary angioplasty, in the PCI group (16.8% versus 10.5%).The number of coronary vessels treated per patient was higher in the BITA group (3.4 versus 1.2; p0.001). Thirty-day mortality was similar: 3.4% in the BITA group and 2.8% in the PCI group. Late follow-up (3 to 6.5 years) showed decreased return of angina (11% versus 64%; p0.001), fewer reinterventions (2.7% versus 55%; p0.001), and increased cardiovascular event-free survival (80% versus 30%; p0.001) in the BITA group. Six-year survival of BITA and PCI patients was 85.5% and 81.2%, respectively (not significant). However, survival of the subgroups of patients with left main or three-vessel coronary artery disease was significantly better with BITA (86% versus 76%; p = 0.003).Despite higher risk profile of diabetic patients treated surgically by BITA, their late outcome is better than that of patients treated by PCI. The results of this study support referring diabetics with single-vessel or double-vessel disease to PCI and those with three-vessel and left main coronary artery disease to surgery.

Background Coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI) is associated with increased mortality compared with CABG in non-AMI patients. Operating without cardiopulmonary bypass (CPB) might reduce this mortality. Methods Between January 1992 and December 1998, 225 patients underwent CABG within 7 days of AMI, 119 with CPB and 106 without. The two groups were similar regarding age, gender, left ventricular dysfunction, and incidence of cardiogenic shock. Mean number of grafts per patient was 3.1 in the CPB group, and 1.7 in the no-CPB group ( p Results Operative mortality in the CPB group was 12% compared with 3.8% without CPB ( p = 0.027). Independent predictors of operative mortality were preoperative use of intraaortic balloon counterpulsation (IABP), nonuse of internal thoracic artery (ITA) to the left anerior descending artery, and the use of less than three grafts. Mortality of patients operated on with CPB within 48 hours of AMI was significantly higher (16.5% vs 4.3%, respectively; p = 0.044). However, patients operated on after 48 hours had similar mortality (5.8% vs 3.4%, respectively). Follow-up ranged from 6 to 84 months. Five-year survival (Kaplan-Meier) of both groups was similar (81%). Patients operated on with CPB had similar rates of recurrent angina; however, they had lower prevalence of reinterventions (0.8% vs 6.3%; p = 0.03). Conclusions Our study suggests that CPB can be used safely for most patients referred for CABG within the first week of AMI. However, for emergency patients operated on within the first 48 hours of symptom onset, we advocate avoiding CPB because it is associated with lower operative mortality.

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.

Objectives Several factors may increase the risk of stroke during coronary artery bypass grafting. These include age and atherosclerosis, which are not modifiable, and aortic manipulation, which may be modifiable. This study reports our experience with variable degrees of aortic manipulation (ie, single vs double [partial occlusion] aortic crossclamp techniques) and its influence on rate of operative stroke. Methods We performed a retrospective review of 8497 patients treated with isolated on-pump coronary artery bypass grafting from 1993 to 2010. Demographics included an age of 66.8 ± 10.3 years and male sex in 6548 patients (77.1%). Operative technique used the single aortic crossclamp in 2051 patients (24.1%) and the partial aortic crossclamp in 6446 patients (75.9%). To adjust for differences in baseline patient characteristics, 2 propensity-matched cohorts of 1333 patients each were created using Society of Thoracic Surgeons risk calculator variables. Results In the unmatched cohorts, stroke occurred in 25 patients (1.2%) in the single aortic crossclamp cohort and in 98 patients (1.5%) in the partial aortic crossclamp cohort ( P = .320). Logistic regression analysis demonstrated no significant relationship between stroke and aortic occlusion clamp technique (single clamp odds ratio, 0.80; 95% confidence interval, 0.51-1.24; P = .321). In the matched cohorts, stroke occurred in 16 patients (1.2%) in both the single and partial occlusion clamp cohorts ( P = 1.00). Conclusions Given the methods and limitations of the data analysis, the single and partial aortic crossclamp techniques result in similar rates of stroke during on-pump coronary artery bypass grafting.

Objectives: Composite arterial grafting is a surgical technique for arterial myocardial revascularization, in which free arterial conduits are proximally anastomosed end-to-side to an intact internal thoracic artery (ITA). This report describes technical aspects and results of composite grafting using bilateral skeletonized ITAs. Methods: From April 1996 to February 1999, 1057 patients underwent coronary artery bypass grafting (CABG) using bilateral skeletonized internal thoracic arteries. In 600 of them (57%), composite arterial grafting was performed. There were 452 men and 148 women. The mean age was 69 ^ 7 years. Two-hundred and six patients (34%) were diabetics, 84 (14%) had severe left ventricular dysfunction (ejection fraction of ,35%), and 26 (4.3%) underwent emergency operations. In 574 patients, the right ITA was used as a free graft connected to the in-situ left ITA. In 26, the free left ITA was attached to the in-situ right ITA, and in 38, mini-composite grafts (free distal left ITA on the left ITA, or free distal right ITA on the right ITA) were constructed. The average number of grafts was 3.0/patient (range, 2‐6). Results: The operative mortality was 2.8% (na 17), and there were ten (1.7%), deep sternal wound infections. The mean follow-up was 25 months (range, 14‐36 months). The 3-year survival was 92.5%. Ninety-seven percent of the surviving patients were angina-free. Conclusions: We currently perform this surgery routinely in most patients referred for CABG, and regard bilateral skeletonized internal thoracic arteries as the most appropriate arterial conduits for the composite technique. q 2001 Elsevier Science B.V. All rights reserved.

Objectives: Higher patency rates of the internal thoracic artery have led myocardial revascularization with bilateral internal thoracic arteries to be a procedure designated primarily for young patients. Fewer leg wound complications and sternal collateral flow preservation with the skeletonizing dissection technique can make bilateral internal thoracic artery grafting attractive also for elderly patients. Methods: Between May 1996 and May 1998, 303 consecutive patients aged 70 years or older (mean age 75.5 years; range 70-92 years) underwent coronary artery bypass grafting with double skeletonized internal thoracic arteries. Forty-four (14.5%) patients were 80 years or older, and 89 (28%) had diabetes. The mean number of grafts was 3.1 per patient (2-6). Results: Operative mortality was 2.6% (n = 8): it was higher for octogenarians (6.8%) than for younger patients (1.9%) ( P =.06). The only significant preoperative predictors of early mortality were complicated percutaneous transluminal coronary angioplasty ( P =.03) and preoperative use of intra-aortic balloon pumping ( P =.03). Six patients (2%) had sternal wound infections for which chronic lung disease ( P =.02) and emergency operation ( P =.006) were the only significant predictors. Twenty-two (7.2%) late deaths occurred, and 1- and 3-year survivals were 93% and 90%, respectively. The 3-year survival of patients 80 years old or older was 92%. Conclusions: Bilateral grafting of the skeletonized internal thoracic artery carries relatively low morbidity and mortality in elderly patients and can be recommended for selected patients including octogenarians. (J Thorac Cardiovasc Surg 2000;120:290-7)

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.

New coronary artery revascularization strategies are developing: improved quantification of coronary artery disease by the SYNTAX score, new-generation drug-eluting stents and increased use of stents for multivessel disease, ongoing evaluation of stents for left main disease, new strategies for minimally invasive coronary artery bypass grafting (CABG) including the use of robotic-assisted CABG, hybrid procedures, and off pump CABG. In comparisons of all these strategies, the impact on survival is arguably the most important parameter. It has long been accepted that using the left internal mammary artery (LIMA) to bypass the left anterior descending coronary artery (LAD) is the gold standard and may confer the survival advantage reported for CABG compared with percutaneous coronary intervention in the literature. The survival advantage of using additional arterial conduits as compared to the conventional use of LIMA with saphenous veins only has long been debated. Our study, which involved a large cohort of 8,622 patients with multivessel disease, followed over a long period of time, has shown that in primary isolated CABG surgery performed more than 15 years ago with the use of LIMA to the LAD, bypassing the non-LAD targets with at least 1 additional arterial graft, either the right internal mammary artery and/or the radial artery, was an independent predictor of increased survival during the following 15 years. The results were confirmed with both a propensity-matched analysis that included 1,153 patients in each group and a multivariate analysis that was able to control for all differences between the groups because of the power of the large cohort in this series. The significant survival advantage of coronary artery bypass surgery with the use of multiple arterial grafting cannot be ignored in patients with multivessel coronary artery disease as various revascularization strategies are considered.

To compare long-term survival with multiple arterial coronary artery bypass grafting (CABG) (MultArt) versus percutaneous coronary intervention (PCI) in patients with multivessel disease (MVD).We reviewed 12,615 patients with MVD with isolated primary CABG or PCI from 1993 to 2009. Patients with CABG (n = 6667) were grouped according to the number of arterial grafts into left internal thoracic artery (LITA)/saphenous vein (SV) (n = 5712) or MultArt (n = 955); patients with PCI (n = 5948) were grouped into balloon angioplasty (BA) (n = 1020), drug-eluting stent (DES) (n = 1686), and bare metal stent (BMS) (n = 3242).Unadjusted long-term survival was lower for CABG than PCI (15-year survival, 34% vs 46%; P .001); however, in patients with MultArt, survival was greater than LITA/SV, BA, BMS (15-year survival, 65% vs 31%, 47%, 45%, respectively; P .001), and DES (8-year survival, 87% vs 70%; P .001). In matched analyses, 15-year survival of MultArt was higher than BA (66% vs 57%; P = .002), LITA/SV (64% vs 56%; P = .02), and BMS (5-year survival 94% vs 90%; P = .01), and similar to DES at 8 years. In multivariate analysis, compared with MultArt, LITA/SV had worse survival (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09-1.52; P = .003). BMS (HR, 0.87; 95% CI, 0.80-0.94; P .001) and DES (HR, 0.76; 95% CI, 0.66-0.88; P .001) had improved survival versus LITA/SV but not versus MultArt (HR, 1.12; 95% CI, 0.94-1.34; P = .21, and HR, 0.98; 95% CI, 0.79-1.21; P = .83, respectively). Secondary analyses for treatment crossover indicated lower survival for LITA/SV versus MultArt and PCI.In patients with MVD undergoing primary revascularization, MultArt increased survival benefit versus LITA/SV compared with PCI. Use of MultArt must increase.

Objectives: Sepsis and septic shock are major causes of morbidity and mortality in critically-ill patients. Sepsis constitutes the systemic response to infection, that is predominantly mediated by the pro-inflammatory cytokines TNF-α and IL-1β. Hence, cytokine modulation provides a promising target for the treatment of sepsis. In this work we evaluated the effect of a low-dose Vipera aspis venom (VAV) vaccine on survival and cytokine serum levels in a rat model of lipopolysaccharide (LPS)-induced septic shock. Methods: Adult male Wistar rats were given either VAV vaccine or saline, and 2 weeks later half of each group received LPS challenge, and were monitored for mortality, cytokine levels, blood count and chemistry. Results: Survival rate was significantly higher in venom-treated, compared to non-vaccinated septic rats. Furthermore, VAV treatment significantly reduced LPS-associated TNF-α and LDH, without affecting IL-6 and IL-10 levels, and modified WBC and platelet counts. Conclusions: Our data suggest that sub-toxic doses of VAV have a protective effect against LPS-induced septic shock that may be mediated, at least partially, by the modulated TNF-α activity. This study thus offers a novel therapeutic approach for the attenuation of bacteremia-induced septic shock through the modulation of a central pro-inflammatory cytokine by VAV vaccination in mammals.

Background Occasionally pulmonary artery banding is necessary to reduce pulmonary arterial blood flow and pressure in patients who cannot be repaired in a single stage. Traditional extraluminal PAB can be associated with significant morbidity. We describe our technique, applications, and results of endoluminal pulmonary artery banding (EPAB) with and without creation of an aortopulmonary window (APW) for complex cardiac anomalies. Methods Thirty-two patients underwent EPAB; 20 patients had simultaneous creation of an APW. Median patient age was 40 days (range, 2 to 3,210); median weight was 3.5 kg (range, 2.4 to 23 kg). Endoluminal pulmonary artery banding fenestrations of 2 to 8 mm were centrally placed in a Dacron patch that was attached circumferentially and intraluminally in the main pulmonary artery. Fenestrations were sized by presence of APW and patient weight. Thirty-one of 32 patients underwent associated cardiac procedures. The mean follow-up period was 2.6 years (range, 0 to 15.5). Results Overall early mortality was 31% (10 of 32); 8% in EPAB alone (1 of 12) and 45% for EPAB+APW (9 of 20). Of the early deaths, 7 of 10 had severe, preoperative ventricular dysfunction. There was 1 early EPAB-related complication requiring band revision for relief of partial obstruction of the APW. At hospital dismissal, the mean pressure gradient after EPAB was 55.1 ± 8.4 mm Hg as assessed by echocardiography. No patient experienced distal pulmonary hypertension, distortion, or band occlusion. There were 6 late deaths. At late follow-up, 5 patients underwent band revision, and complete repair was accomplished in 10 patients. Conclusions Endoluminal pulmonary artery banding provided a consistently effective and durable reduction in pulmonary arterial blood flow with no pulmonary artery distortion. Early mortality was low for EPAB alone. Endoluminal pulmonary artery banding alone is preferred when controlled pulmonary blood flow and cardiopulmonary bypass are required to address intracardiac abnormalities. The role of EPAB with APW needs to be defined.

Background: The use of the radial artery (RA) in coronary bypass operations has become increasingly popular in recent years, but there is almost no documentation regarding the midterm and long-term arm complications. Methods: Between January 1 and December 31, 1998, 109 patients underwent operations for myocardial revascularization employing a pedicled RA as 1 of the coronary grafts. The patients were surveyed for subjective arm morbidities at 2 times during their follow-up: short term (mean, 7 months postoperatively; range, 0.3-14 months) and long term (mean, 49 months postoperatively; range, 46-57 months). Results: At the short-term follow-up, 33 (33.3%) of the patients had some complaints regarding the arm that was operated on, with 4 (4%) of the patients reporting arm disability with complaints that focused on pain (11, 11%), numbness (15, 15%), and parasthesias (12, 12%). At the long-term follow-up, only 9 patients (10.5%) still experienced some sort of inconvenience with the arm that was operated on, with 1 case of functional disability, 4 complaints (4.6%) of residual parasthesias, and 1 report (2.3%) each of pain or numbness. All but 2 of the patients with complaints at the short-term follow-up reported amelioration of symptoms at the long-term follow-up. Conclusion: It appears that severe arm disability early after RA harvesting is likely to dissolve with time. Our favorable late follow-up results support the continuation of the employment of the RA as a conduit for coronary artery bypass grafting operations.

Acute aortic dissection (AAD) is a life-threatening condition for which prompt diagnosis is essential for successful management. The imaging modalities for demonstrating the dissecting membrane include retrograde aortography, contrast-enhanced computed tomography (CT), transesophageal echocardiography (TEE), and magnetic resonance imaging. Of these, aortography had long been considered the gold standard in diagnosing aortic dissection. We present a case of AAD in which contrast-enhanced CT and retrograde aortography failed to demonstrate an aortic membranous flap, whereas TEE swiftly provided clear-cut evidence of the pathology. TEE should be considered when AAD is suspected despite negative findings on other imaging modalities.

Background: Skeletonized dissection of the internal thoracic artery (ITA) decreases the occurrence of sternal devascularization, thus decreasing the risk of postoperative sternal complications in patients undergoing bilateral ITA grafting. Methods: From April 1996 to July 1999, 1000 consecutive patients underwent bilateral skeletonized ITA grafting. Of the 770 male and 230 female patients, 420 were older than 70 years, and 312 had diabetes. Results: Operative mortality was 3.3%. Follow-up (4078 months) revealed 79 late deaths, and the Kaplan-Meier 6-year survival rate was 88%. Cox regression analysis revealed increased overall mortality (early and late) in patients with preoperative congestive heart failure (risk ratio [RR], 2.13; 95% confidence interval [CI], 1.31-3.45), in patients with peripheral vascular disease (RR, 5.52; 95% CI, 3.31-9.19), and in patients older than 70 years (RR, 2.18; 95% CI, 1.37-3.47). Early postoperative morbidity included sternal infection (2.2%), cerebrovascular accident (1.6%), and perioperative myocardial infarction (1%). Multiple regression analysis showed repeat operation (odds ratio [OR], 7.5; 95% CI, 1.77-31.6) and chronic obstructive pulmonary disease (OR, 3.6; 95% CI, 1.27-10.75) to be independent predictors of sternal infection. During follow-up, angina returned in 95 patients, 24 of whom required reintervention (20 cases of percutaneous balloon angioplasty and 4 reoperations). Postoperative coronary angiography performed in 87 patients revealed an ITA patency rate of 91%. Conclusions: Bilateral skeletonized ITA grafting is associated with satisfactory early and midterm results. We do not recommend the use of this surgical technique in patients with chronic obstructive pulmonary disease.

Background: Detection of severe atherosclerotic ascending aorta during coronary artery bypass grafting requires alterations in the standard surgical technique to reduce the probability of stroke-related atheroembolization. Off-pump coronary artery bypass grafting (OPCAB) confers the benefits of avoiding aortic cannulation and clamping, and may therefore attenuate this risk. Methods: OPCAB (n # 41) was compared to cardiopulmonary bypass (CPB) using femoral arterial cannulation and hypothermic fibrillatory arrest (n = 15), in patients with porcelain ascending aorta undergoing myocardial revascularization. In both groups, a ‘no touchrsquo; technique was applied by avoiding aortic cannulation and clamping. Proximal anastomoses on the atherosclerotic aorta were avoided by arterial grafting, (in-situ or T-graft configurations) in all cases. Results: Operative mortality was comparable (2.4% and 6.6% in the OPCAB and CPB groups respectively, p # NS). The rate of adverse neurological events, (two strokes and one transient ischemic attack), was higher in the CPB group (p # 0.0164). Based on brain CT, the nature of the recorded stroke suggested retrograde emboli. Three year survival (Kaplan-Meier) for the OPCAB and CPB groups was 86.7% and 81.3%, respectively (p = NS). Occurrence of late neurological adverse events during follow-up (8–51 months) was similar. Conclusions: In patients with porcelain ascending aorta undergoing myocardial revascularization, neurological outcome of OPCAB patients is better than CPB using femoral artery cannulation.

Background The complementary graft of choice to the right coronary artery system in patients undergoing left-sided bilateral internal thoracic artery grafting has yet to be determined. Saphenous vein graft (SVG) was compared with right gastroepiploic artery (RGEA) as the supplemental conduit to the right coronary artery when left-sided bilateral internal thoracic artery grafting is implemented. Methods From April 1996 to July 1999, 234 patients underwent bilateral internal thoracic artery grafting to the left coronary system with RGEA grafted to the posterior descending artery (RGEA group). They were compared with 127 patients with left-sided bilateral internal thoracic artery in whom SVG was used for grafting the right coronary system (SVG group). Results Female sex (27% versus 14.5%), diabetic patients (40% versus 27%), emergency cases (21% versus 7.3%), and left main coronary artery disease (34% versus 23%) were more prevalent in the SVG group. Number of grafts per patient was higher in the SVG group (3.8 versus 3.5, p = 0.04). Thirty-day mortality was 3.9% in the SVG and 2.6% in the RGEA group (not significant). Occurrence of postoperative complications (myocardial infarctions, strokes, bleeding, and sternal infections) was similar. Return of angina was similar (1.6% versus 3.8% in the SVG and RGEA groups, respectively). Midterm follow-up (4 to 56 months) showed comparable 1-year and 4-year survival (Kaplan-Meier) for both groups (92.8% and 91.7% in the SVG group, and 94.7% and 88% in the RGEA group, respectively). Conclusions In patients undergoing left-sided bilateral internal thoracic artery grafting, the use of RGEA for revascularization of the right coronary system does not confer clinical benefits over SVG after midterm follow-up.

Objective: The left internal thoracic artery (LITA) is the most important graft for coronary artery bypass grafting (CABG). Its distal region is, however, prone to vasospasm. The effect of nitroglycerin (NTG) and isosorbide-dinitrate (ISDN) on different segments of this region was studied. Methods: Rings of three segments of the LITA were studied: 6‐9 mm proximal to the bifurcation (part A); 1‐3 mm proximal to the bifurcation (part B); and 3‐6 mm distal to the bifurcation (part C). After baseline, maximal contraction of the rings was achieved using 60 mmol/l of KCl, they were exposed to increasing doses of ISDN and NTG (10‐100 mg/ml), and dose‐response curves were recorded. Results: The contractile response of part A to KCl was significantly lower than that of parts B and C (1.87 ^ 0.25 versus 4.05 ^ 0.39 and 7.64 ^ 0.54 g, respectively; P , 0:001). Both nitrates inhibited the contractile response in a concentration-dependent manner. The relaxing effects of both nitrates on part A was most pronounced (P , 0:01), with the effect of ISDN being higher than that of NTG (P , 0:01). Conclusions: The region 6‐9 mm proximal to the LITA bifurcation is less prone to vasospasm, and has greater relaxation responses to ISDN and NTG than the more vasospastic distal parts of the LITA. We recommend avoiding the use of the very distal part of this artery during CABG, and to use high doses of ISDN rather than NTG as an anti-spastic measure. q 2001 Elsevier Science B.V. All rights reserved.

Background . Protamine is commonly used in cardiac surgery to reverse the anticoagulant effects of heparin. We investigated the role of different nitric oxide synthase pathways in the response of the human internal thoracic artery to protamine and evaluated whether heparin could prevent this effect. Methods . A tension-recording method was used to obtain baseline measurements of contractions of human internal thoracic artery rings achieved with norepinephrine. Isolated internal thoracic artery rings were suspended in two organ chambers. One contained Krebs-Henseleit solution and served as control. The other contained a heparin or Nω-Nitro-L-arginine (L-NAM, an inhibitor of both endothelial and inducible nitric oxide synthase) or a specific inhibitor of inducible nitric oxide synthase, aminoguanidine. Increasing doses of protamine were added to both chambers and dose-response curves were obtained. Results . Protamine was found to relax contracted internal thoracic arteries 56% ± 4.7% of baseline measurements in a concentration-dependent manner. When L-NAM was added, protamine caused only a slight decrease of tension. There were no differences in the relaxing effect of protamine in the presence of aminoguanidine or heparin. Conclusions . Protamine induces nitric oxide-dependent relaxation of the internal thoracic artery by activation of endothelial nitric oxide synthase pathway. Heparin could not prevent this relaxing effect of protamine.

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 NoCPB 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 NoCPB 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.

Increasing evidence suggests that a locally integrated or intramyocardial renin-angiotensin system plays a significant role in ischemia-reperfusion injury. We evaluated the effects of losartan, an angiotensin II type 1 receptor blocking agent, on ischemic and nonischemic isolated rat hearts.Using the modified Langendorff model, hearts were perfused with either low or high doses of losartan (18.2 mmol/L or 182.2 mmol/L, respectively) or with saline added to Krebs-Henseleit solution during phase I of the study. During phase II, hearts were exposed to a 60-minute period of global ischemia. Ischemic arrest was induced with warm cardioplegic solution (KCl, 16 mEq/L) containing either high-dose losartan (182.2 mmol/L) or Krebs-Henseleit solution only.During phase I of the study, no statistically significant differences were observed between the low-dose losartan group and the control group. However, hearts treated with high-dose losartan demonstrated an increase in peak systolic pressure, maximum first derivative of pressure, pressure-time integral, coronary flow, and oxygen consumption (p0.0001). During phase II, hearts treated with losartan showed a significantly better recovery on reperfusion, as reflected by better contractility (p0.001), higher oxygen consumption (p0.001), higher coronary flow (p0.0001), and lower creatine phosphokinase levels (41.1 +/- 1.7 versus 73.3 +/- 5.6 U/L; p0.001).High doses of losartan have a positive inotropic effect on normally perfused hearts. Given in cardioplegic solution, the drug has a significant protective effect on ischemic isolated rat hearts.

ObjectivesThe present study aimed to investigate the influence of endogenous tumor necrosis factor-alpha (TNF-α) that was synthesized during ischemia and exogenous TNF-α on endothelial and inducible nitric oxide synthase (eNOS and iNOS) messenger ribonucleic acid (mRNA) expression and nitric oxide (NO) production in the isolated rat heart.BackgroundTumor necrosis factor-α is recognized as being a proinflammatory cytokine with a significant cardiodepressant effect. One of the proposed mechanisms for TNF-α-induced cardiac contractile dysfunction is increased NO production via iNOS mRNA upregulation, but the role of NO in TNF-α-induced myocardial dysfunction is highly controversial.MethodsIsolated rat hearts studied by a modified Langendorff model were randomly divided into subgroups to investigate the effect of 1-h global cardioplegic ischemia or the effect of 1-h perfusion with exogenous TNF-α on the expression of eNOS mRNA and iNOS mRNA and on NO production.ResultsAfter 1 h of ischemia, there were significant increases in TNF levels in the effluent (from hearts), and eNOS mRNA expression had declined (from 0.91 ± 0.08 to 0.68 ± 0.19, p < 0.001); but there were no changes in iNOS mRNA expression, and NO was below detectable levels. Perfusion of isolated hearts with TNF-α had a cardiodepressant effect and decreased eNOS mRNA expression to 0.67 ± 0.04 (p < 0.002). Inducible nitric oxide synthase mRNA was unchanged, and NO was below detectable levels.ConclusionsWe believe this is the first study to directly show that TNF-α does not increase NO synthesis and release but does downregulate eNOS mRNA in the ischemic and nonischemic isolated rat heart.

Radial artery (RA) conduits are prone to early vasospasm. Current intraoperative treatment with papaverine fails to inhibit postoperative RA constriction. Pretreatment with topical a-antagonist solutions can inhibit RA vasoconstriction and cause dilatation for a longer period than achieved with papaverine.In 10 patients undergoing myocardial revascularization, the radial artery was harvested as a skeletonized vessel. A composite graft with reverse free RA on an in situ left internal thoracic artery was prepared before construction of distal coronary anastomoses. The RA pedicle was then put in a small syringe filled with Regitine (phentolamine methansulphonic, 0.07 mg/mL) ("Jacuzzi") and warmed by immersing the container in a warm saline bath for 8 to 15 minutes. The RA free flow was measured before and after topical treatment with Regitine.The mean number of grafts per patient was 2.9 (range 2 to 4). The mean number of radial anastomoses was 1.8 per patient. Left internal thoracic artery free flow was 110 +/- 29 mL/min. Regitine increased radial free flow from 49 +/- 35 to 77 +/- 30 mL/min (p0.01). Five patients underwent postoperative coronary angiography. All radial anastomoses were patent.Topical treatment of RA with Regitine increases RA free flow and is an effective intraoperative means of decreasing RA spasticity.

Background: Atherosclerotic or calcified ascending aorta is an important predictor of adverse cerebrovascular events. Using off-pump coronary artery bypass (OPCAB) with composite and in situ arterial grafting to avoid aortic manipulation and clamping may reduce the risk of stroke related to aortic atheroembolism. When the aorta is calcified and cannot serve as a safe site for proximal anastomosis, this anastomosis can be performed on the proximal segment of the right internal thoracic artery (ITA) and right gastroepiploic artery (RGEA). Four such cases are described. Methods: In 2 patients, the proximal right ITA was used as the site for proximal saphenous vein graft (SVG) anastomosis. Chronic obstructive lung disease in one patient and insulin-dependent diabetes in the other precluded performance of OPCAB with bilateral ITA. In addition, positive Allen test precluded performance of composite T-graft with radial artery (RA) on ITA. Both SVGs were anastomosed distally to the posterior descending artery. In 2 other patients, RA was connected end-to-side to the proximal segment of the RGEA. Both of these patients had repeat operations. The distal end of the RGEA was too small, and concerns regarding the future flow to a very large coronary bed precluded its use as an in situ graft. Results: All patients underwent the operative procedures without any neurological or cardiovascular adverse effects, and all are midterm, symptom-free survivors. Postoperative graft patency was confirmed intraoperatively with flow measurements and postoperatively with control angiography or coronary imaging computed tomography. Conclusions: The RITA and proximal RGEA can serve safely as sites for proximal anastomosis in patients with atherosclerotic calcified aorta undergoing OPCAB.