Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure.

BACKGROUND: Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal-flow device) against existing technology (a commercially available axial-flow device) in patients with advanced heart failure who were ineligible for heart transplantation. METHODS: We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal-flow) device or the control (axial-flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. RESULTS: The intention-to treat-population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. CONCLUSIONS: In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal-flow LVAD was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347 .).

Left ventricular assist device management in the ICU.

OBJECTIVES: To review left ventricular assist device physiology, initial postoperative management, common complications, trouble shooting and management of hypotension, and other common ICU problems. DATA SOURCE: Narrative review of relevant medical literature. DATA SYNTHESIS: Left ventricular assist devices prolong the lives of patients with end-stage heart failure, and their use is increasing. Continuous-flow left ventricular assist devices have replaced first-generation pulsatile devices. These patients present unique management concerns. In the immediate postimplant period, care must be taken to support the unassisted right ventricle. Invasive monitors for blood pressure, pulmonary artery catheterization, and echocardiography are essential to optimize left ventricular assist device settings and cardiac performance. Anticoagulation is necessary to prevent devastating thrombotic and embolic complications, but bleeding is a major source of morbidity due to inherent bleeding diatheses and prescribed anticoagulants. Infection of the device can be life threatening, and all infections must be aggressively treated to avoid seeding the device. Patients are at risk of ventricular arrhythmias because of their underlying disease, as well as the placement and position of the inflow cannula. Aortic valve stenosis and insufficiency develop over time and can lead to thrombosis or heart failure. Cardiopulmonary resuscitation with chest compressions must be performed with care or not at all due to risk of dislodging the device. CONCLUSION: Intensivists are increasingly likely to encounter patients requiring mechanical circulatory support with left ventricular assist devices at various points in the trajectory of their disease, from the immediate postimplant period to subsequent admissions for complications, and at end of life. A basic understanding of left ventricular assist device physiology is essential to the safe and effective care of these patients.

Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation.

BACKGROUND: Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. METHODS AND RESULTS: We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. CONCLUSIONS: A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751972.

Patients with severe asymptomatic carotid artery stenosis do not have a higher risk of stroke and mortality after coronary artery bypass surgery.

BACKGROUND AND PURPOSE: Stroke development is a major concern in patients undergoing coronary artery bypass grafting (CABG). Whether asymptomatic severe carotid artery stenosis (CAS) contributes to the development of stroke and mortality in such patients remains uncertain. METHODS: A retrospective analysis of 878 consecutive patients with documented carotid duplex ultrasound who underwent isolated CABG in our institution from January 2003 to December 2009 was performed. Patients with severe CAS (n=117) were compared with those without severe CAS (n=761) to assess the rates of stroke and mortality during hospitalization for CABG. The 30-day mortality rate was also assessed. RESULTS: Patients with severe CAS were older and had a higher prevalence of peripheral arterial disease and heart failure. Patients with severe CAS had similar rates of in-hospital stroke (3.4% versus 3.6%; P=1.0) and mortality (3.4% versus 4.2%; P=1.0) compared with patients without severe CAS. The 30-day rate of mortality was also similar between the 2 cohorts (3.4% versus 2.9%; P=0.51). CONCLUSIONS: Severe CAS alone is not a risk factor for stroke or mortality in patients undergoing CABG. The decision to perform carotid imaging and subsequent revascularization in association with CABG must be individualized and based on clinical judgment.

A randomized, open-label pilot study comparing desirudin and argatroban in patients with suspected heparin-induced thrombocytopenia with or without thrombosis: PREVENT-HIT Study.

Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. Sixteen patients were randomized to treatment with fixed-dose desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time-adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to direct thrombin inhibitor therapy, whereas Arm B included 8 patients on argatroban for at least 24 hours before randomization. The primary efficacy measure was the composite of new or worsening thrombosis (objectively documented), amputation, or death. Other end points included major and minor bleeding while on drug therapy, time to platelet count recovery, and pharmacoeconomics. No amputations or deaths occurred. One patient randomized to argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2 patients on argatroban and in none during desirudin treatment. There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.

Perioperative outcomes in reoperative cardiac surgery guided by cardiac multidetector computed tomographic angiography.

BACKGROUND: Preoperative evaluation with contrast-enhanced multidetector computed tomographic angiography (MDCTA) is considered an "appropriate" indication based on expert consensus. We aimed to evaluate how the presurgical evaluation with MDCTA impacts the outcomes after reoperative cardiac surgery (RCS). METHODS: We retrospectively studied 364 patients undergoing RCS between 2004 and 2008, including 137 referred for MDCTA. High-risk CT findings were defined as the presence of right ventricle or aorta <10 mm from the sternum or a bypass graft <10 mm from the sternum crossing the midline. The primary clinical end point was the composite of perioperative death, myocardial infarction (MI), stoke, and hemorrhage-related reoperation. Secondary end points included surgical procedural variables and the perioperative volume of bleeding and of red blood cell (RBC) transfusion. RESULTS: Baseline clinical characteristics were similar between the 2 groups. Individuals referred for MDCTA showed a trend toward a lower incidence of the composite primary end point (17.5% vs 24.2%, P = .13), primarily related to a significantly lower incidence of perioperative MI (0% vs 5.7%, P = .002). Multidetector computed tomographic angiography was also associated with shorter perfusion (90 vs 110 minutes, P = .002), cross clamp time (63 vs 75 minutes, P = .003), and total time in intensive care unit (103 vs 148 hours, P = .04), and a lower volume of postoperative RBC transfusion (627 vs 824 mL, P = .09). These differences remained significant after adjustment for the Society of Thoracic Surgeons score and the performing surgeon. CONCLUSION: The use of MDCTA before RCS was associated with shorter perfusion and cross clamp time, shorter intensive care unit stays, and less frequent perioperative MI.

Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention with drug-eluting stents for patients with multivessel coronary artery disease.

BACKGROUND: Advances in coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) with drug-eluting stents have dramatically improved results of these procedures. The optimal treatment for patients with multivessel coronary artery disease is uncertain given the lack of prospective, randomized data reflecting current practice. This study represents a "real-world" evaluation of current technology in the treatment of multivessel coronary artery disease. METHODS AND RESULTS: A total of 1680 patients undergoing revascularization for multivessel coronary artery disease were identified. Of these, 1080 patients were treated for 2-vessel disease (196 CABG and 884 PCI) and 600 for 3-vessel disease (505 CABG and 95 PCI). One-year mortality, cerebrovascular events, Q-wave myocardial infarction, target vessel failure, and composite major adverse cardiovascular and cerebrovascular events were compared between the CABG and PCI cohorts. Outcomes were adjusted for baseline covariates and reported as hazard ratios. The unadjusted major adverse cardiovascular and cerebrovascular event rate was reduced with CABG for patients with 2-vessel disease (9.7% CABG versus 21.2% PCI; P<0.001) and 3-vessel disease (10.8% CABG versus 28.4% PCI; P<0.001). Adjusted outcomes showed increased major adverse cardiovascular and cerebrovascular event with PCI for patients with 2-vessel (hazard ratio 2.29; 95% CI 1.39 to 3.76; P=0.01) and 3-vessel disease (hazard ratio 2.90; 95% CI 1.76 to 4.78; P<0.001). Adjusted outcomes for the nondiabetic subpopulation demonstrated equivalent major adverse cardiovascular and cerebrovascular event with PCI for 2-vessel (hazard ratio 1.77; 95% CI 0.96 to 3.25; P=0.07) and 3-vessel disease (hazard ratio 1.70; 95% CI 0.77 to 3.61; P=0.19). CONCLUSIONS: Compared with PCI with drug-eluting stents, CABG resulted in improved major adverse cardiovascular and cerebrovascular event in patients with 2- and 3-vessel coronary artery disease, primarily in those with underlying diabetes. Coronary artery bypass surgery may be the preferred revascularization strategy in diabetic patients with multivessel coronary artery disease.

Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery.

BACKGROUND: Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG. METHODS: In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications. RESULTS: As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4 percent in each of these two groups vs. 4.0 percent in the placebo group; risk ratio for each comparison, 1.9; 95 percent confidence interval, 1.1 to 3.2; P=0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0 percent vs. 0.5 percent; risk ratio, 3.7; 95 percent confidence interval, 1.0 to 13.5; P=0.03). CONCLUSIONS: The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.

Early readmission of low-risk patients after coronary surgery.

BACKGROUND: Early readmission after coronary artery bypass grafting (CABG) is an expensive adverse outcome. Although the perioperative experience of high-risk CABG patients has been studied extensively, little attention has been paid to low-risk CABG patients. The primary goal of this study was to identify the preoperative characteristics and to define risk predictors of readmission and preventive factors for readmission in low-risk isolated-CABG patients. METHODS: We identified 2157 patients who underwent CABG between January 2000 and December 2005 at Washington Hospital Center, Washington, DC, and defined as low risk patients who had a Parsonnet bedside risk score lower than the 25th percentile. Patients who were rehospitalized within 30 days after surgery were compared with those who were not rehospitalized during this period. RESULTS: The overall readmission rate for this study cohort was 6.3%. Compared with non-readmitted patients, early-readmitted patients were more likely to have diabetes mellitus (27.94% versus 20.88%, P = .05) and less likely to have hypertension (42.65% versus 51.36%, P = .05). Blood product transfusion (P < .01), postoperative length of intensive care unit stay (P = .01), and length of hospital stay (P = .05) were all significantly increased in the readmitted patients. The use of beta-blockers (P = .03) and angiotensin-converting enzyme inhibitors (P = .04) was significantly lower at discharge in this group of patients; however, multivariate regression analysis demonstrated diabetes (odds ratio, 1.59; 95% confidence interval, 1.08-2.42) to be the only independent predictor of early readmission. CONCLUSIONS: For low-risk CABG patients, diabetes mellitus is the risk predictor of early readmission. Early discharge was not associated with early readmission.

Effect of clopidogrel premedication in off-pump cardiac surgery: are we forfeiting the benefits of reduced hemorrhagic sequelae?

BACKGROUND: Premedication with clopidogrel has reduced thrombotic complications after percutaneous coronary revascularization procedures. However, because of the enhanced and irreversible platelet inhibition by clopidogrel, patients requiring surgical revascularization have a higher risk of bleeding complications and transfusion requirements. A principal benefit of surgical coronary revascularization without cardiopulmonary bypass is its lower hemorrhagic sequelae. The purpose of this study was to evaluate the effect of preoperative clopidogrel administration in the incidence of hemostatic reexploration, blood product transfusion rates, morbidity, and mortality in patients undergoing off-pump coronary artery bypass graft surgery using a large patient sample and a risk-adjusted approach. METHODS AND RESULTS: Two hundred eighty-one patients (17.9%) did and 1291 (82.1%) did not receive clopidogrel before their surgery, for a total of 1572 patients undergoing isolated off-pump coronary artery bypass graft surgery between January 2000 and June 2002. Risk-adjusted logistic regression analyses and a matched pair analyses by propensity scores were used to assess the association between clopidogrel administration and reoperation as a result of bleeding, intraoperative and postoperative blood transfusions received, and the need for multiple transfusions. Hemorrhage-related preoperative risk factors identified in the literature and those found significant in a univariate model were used. The clopidogrel group had a higher likelihood of hemostatic reoperations (odds ratio [OR], 5.1; 95% confidence interval [CI], 2.47 to 10.47; P<0.01) and an increased need in overall packed red blood cell (OR, 2.6; 95% CI, 1.94 to 3.60; P<0.01), multiple unit (OR, 1.6; 95% CI, 1.07 to 2.48; P=0.02), and platelet (OR, 2.5; 95% CI, 1.77 to 3.66; P<0.01) transfusions. Surgical outcomes and operative mortality (1.4% versus 1.4%; P=1.00) were not statistically different. CONCLUSIONS: Clopidogrel administration in the cardiology suite increases the risk for hemostatic reoperation and the requirements for blood product transfusions during and after off-pump coronary artery bypass graft surgery.

Comparisons of cardiac surgery outcomes in Jehovah's versus Non-Jehovah's Witnesses.

Jehovah's Witnesses is a Christian faith whose members will not accept blood or blood products under any circumstances on the basis of religious grounds. To date, no comparative studies have evaluated the outcome of open heart surgery in Jehovah's Witnesses compared with patients who accept the transfusion of blood products. The present study was conducted to systematically compare the operative mortality and early clinical outcome after open cardiac surgery in Jehovah's Witnesses versus non-Jehovah's Witnesses. From January 1990 to July 2004, 49 Jehovah's Witness patients underwent cardiac surgery, and their data were compared with those of a contemporaneous control group of 196 non-Jehovah's Witnesses. Logistic regression analysis was used to compare operative mortality, postoperative intensive care unit care, and hospital length of stay between the 2 groups, controlling for preoperative risk factors. The Jehovah's Witnesses were matched in a 1:4 ratio to the non-Jehovah's Witnesses using propensity scores. No significant differences were identified in unadjusted stroke (p = 0.5), acute myocardial infarction (p = 0.6), new-onset atrial fibrillation (p = 0.106), prolonged ventilation (p = 0.82), acute renal failure (p = 0.70), and hemorrhage-related reexploration (p = 0.59) rates between the 2 groups. On multivariate analysis, Jehovah's Witnesses had operative mortality (odds ratio 0.66, 95% confidence interval 0.12 to 3.59, p = 0.63), intensive care unit stay (odds ratio 1.36, 95% confidence interval 0.46 to 3.97, p = 0.58), and postoperative length of stay (odds ratio 1.43, 95% confidence interval 0.92 to 2.20, p = 0.16) comparable to those of the non-Jehovah's Witnesses, after controlling for preoperative risk factors through matching. In conclusion, cardiac surgery in Jehovah's Witnesses is associated with clinical outcomes comparable to those of non-Jehovah's Witnesses by adhering to blood conservation protocols.

Patients Awaiting Heart Transplantation on HVAD Support for Greater Than 2 Years.

Advanced heart failure patients who are classified as bridge to transplant (BTT) often remain on mechanical circulatory support (MCS) for long durations because of the limited supply of donor organs. Here, we present the outcomes of patients who have been supported by the HeartWare ventricular assist device system for more than 2 years. In the HeartWare BTT and continued access protocol trial, 74 of the 382 total patients (19.4%) had more than 2 years of MCS with a mean time of 1,045 days on device. The long-term group was more frequently female, was nonwhite, and had Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7. Postimplant adverse event rates including bleeding, cardiac arrhythmia, infection, stroke, renal dysfunction, and right heart failure were less frequent in the long-term cohort. In addition, the long-term cohort displayed significant improvements in Kansas City Cardiomyopathy Questionnaire Overall Summary Score, EuroQOL-5D Overall Health State Score, and 6 minute walk scores from baseline values. The rate of heart transplantation was lower for the long-term cohort, which may have been a result of their sex and blood type. However, most of these patients are still listed for cardiac transplantation and maintained their quality of life profiles through 3 years of support.

Chronologic distribution of stroke after minimally invasive versus conventional coronary artery bypass.

OBJECTIVES: We sought to investigate whether the chronologic distribution of the onset of stroke occurring after coronary artery bypass graft surgery (CABG) without cardiopulmonary bypass (off-pump CABG) is different from the conventional on-pump approach (CABG with cardiopulmonary bypass). BACKGROUND: Off-pump CABG has been associated with a lower stroke rate, compared with conventional on-pump CABG. However, it is unknown whether the chronologic distribution of the onset of stroke is different between the two approaches. METHODS: We evaluated the chronologic distribution of postoperative stroke in patients undergoing CABG from June 1996 to August 2001 (n = 10,573). Preoperative risk factors for stroke were identified using the Northern New England preoperative estimate of stroke risk. Multivariate logistic regression analysis was used to determine the independent predictors of early stroke and to delineate the association between the surgical approach and the chronologic distribution of the onset of stroke. RESULTS: Stroke occurred in 217 patients (2%, n = 10,573). A total of 44 (20%) and 173 (80%) of these patients had stroke after off-pump CABG and on-pump CABG, respectively. The median time for the onset of stroke was two days (range 0 to 11 days) after on-pump CABG versus four days (range 0 to 14 days) after off-pump CABG (p < 0.01). On-pump CABG was associated with a higher risk of early stroke (odds ratio 5.3, 95% confidence interval 2.6 to 10.9; p < 0.01) compared with off-pump CABG. CONCLUSIONS: Compared with off-pump CABG, on-pump CABG is associated with an earlier onset of postoperative stroke during the recovery phase, suggesting different mechanisms in the pathogenesis of stroke between the two surgical approaches.

One-year outcome after combined coronary artery bypass grafting and transmyocardial laser revascularization for refractory angina pectoris.

Long-term outcomes after coronary artery bypass graft surgery (CABG) plus transmyocardial revascularization (TMR) are largely unknown. We report the results of 30-day and 3-, 6-, and 12-month clinical follow-up after CABG plus TMR in a consecutive series of patients with refractory angina pectoris and > or = 1 myocardial ischemic area not amenable to CABG. All patients who underwent CABG plus TMR (n = 169) (mean age 63 +/- 10 years, 70% men, 51% with previous CABG, 82% were deemed inoperable at other heart surgery centers due to small vessels or diffuse disease) between March 1996 and February 2000 were clinically followed and end points of interest (survival, stroke, acute myocardial infarction, and revascularization) and angina class were recorded at 30 days and 3, 6, and 12 months after CABG. At 1 year, actuarial survival and event-free survival were 85% and 81%, respectively. At the end of the first year after the procedure, 7 patients (4%) had angina class III/IV versus 152 patients (90%) at baseline (p <0.001). Predictors of major adverse cardiac events were advanced age (odds ratio [OR] 3.4, 95% confidence intervals [CI] 1.2 to 9.4, p = 0.01), prolonged intensive care unit stay (OR 3.3, CI 1.1 to 9.7, p <0.001), new-onset atrial fibrillation (OR 2.8, CI 1.1 to 7.0, p = 0.02), and in-hospital myocardial infarction (OR 1.5, CI 1.3 to 1.7, p <0.001). Thus, procedural success at 30 days and overall event-free and actuarial survival in a high-risk population setting shows that CABG plus TMR is a safe revascularization option for patients with intractable angina pectoris.

Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: results of the CABG surgery cohort of the GUARDIAN study.

OBJECTIVES: To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk of myocardial necrosis after coronary artery bypass graft surgery. METHODS: In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients > or =18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and > or =2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint. RESULTS: Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P =.027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P =.005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P =.033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population. CONCLUSIONS: Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.

Stroke after conventional versus minimally invasive coronary artery bypass.

BACKGROUND: Postoperative stroke is a serious complication after coronary artery bypass grafting with cardiopulmonary bypass (on-pump), and portends higher morbidity and mortality. It is unknown whether an off-pump cardiopulmonary bypass (OPCAB) approach may yield a lower stroke rate over conventional on-pump coronary artery bypass grafting. METHODS: From June 1994 to December 2000, OPCAB was performed in 2,320 patients and compared with 8,069 patients who had on-pump coronary artery bypass grafting, during the same period of time. The patients undergoing OPCAB were randomly matched to on-pump patients by propensity score. A logistic regression model was used to test the difference in the postoperative stroke rate between OPCAB and on-pump procedures controlling for the correlation between matched sets. A multiple logistic regression model predicting the risk of stroke adjusted by stroke risk factors and operation type was also computed. RESULTS: Matches by propensity score were found for 72% of the patients undergoing OPCAB. Patients undergoing on-pump coronary artery bypass grafting were 1.8 (95% confidence interval 1.0 to 3.1, p = 0.03) times more likely to suffer a stroke postoperatively than OPCAB patients after controlling for preoperative risk factors through matching. Independent predictors of stroke identified from the multiple logistic model included on-pump operation (versus OPCAB operation), female gender, 4 to 6 vessels grafted (versus <4 grafts), hypertension, history of previous cerebrovascular accident, carotid artery disease, chronic obstructive pulmonary disease, and depressed ejection fraction. CONCLUSIONS: Off-pump cardiopulmonary bypass avoids the risks of cardiopulmonary bypass and atrial trauma. A substantially lower stroke rate suggests that OPCAB is a neurologically safe treatment option for revascularization.

Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass.

BACKGROUND: During cardiac surgery requiring cardiopulmonary bypass, pro-inflammatory complement pathways are activated by exposure of blood to bio-incompatible surfaces of the extracorporeal circuit and reperfusion of ischemic organs. Complement activation promotes the generation of additional inflammatory mediators thereby exacerbating tissue injury. We examined the safety and efficacy of a C5 complement inhibitor for attenuating inflammation-mediated cardiovascular dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass. METHODS: Pexelizumab (Alexion Pharmaceuticals, Inc, Cheshire, CT), a recombinant, single-chain, anti-C5 monoclonal antibody, was evaluated in a randomized, double-blinded, placebo-controlled, multicenter trial that involved 914 patients undergoing coronary artery bypass grafting with or without valve surgery requiring cardiopulmonary bypass. RESULTS: Pexelizumab was administered intravenously as a bolus (2.0 mg/kg) or bolus plus infusion (2.0 mg/kg plus 0.05 mg/kg/h for 24 hours), and inhibited complement activation. There were no statistically significant differences between placebo-treated and pexelizumab-treated patients in the primary endpoint (composite of death, or new Q-wave, or non-Q-wave [myocardial-specific isoform of creatine kinase > 60 ng/mL] myocardial infarction, or left ventricular dysfunction, or new central nervous system deficit). However, post hoc analysis revealed a reduction in the composite of death or myocardial infarction (myocardial-specific isoform of creatine kinase >/= 100 ng/mL) for the isolated coronary artery bypass grafting, bolus plus infusion subgroup on POD 4 (p = 0.007) and on POD 30 (p = 0.004). CONCLUSIONS: Pexelizumab had no statistically significant effect on the primary endpoint. However, the reduction in death or myocardial infarction (myocardial-specific isoform of creatine kinase >/= 100 ng/mL) as revealed in the post hoc analysis in the isolated coronary artery bypass grafting bolus plus infusion subpopulation, suggests that further investigation of anti-C5 therapy for ameliorating complement-mediated inflammation and myocardial injury is warranted.

Operative mortality after conventional versus coronary revascularization without cardiopulmonary bypass.

OBJECTIVE: Off-pump coronary artery bypass (CABG) is a safe revascularization option with comparable or superior results to the conventional on-pump CABG. However, comparative analysis of the type of surgical approach on the mortality rate is largely unknown. This study sought to investigate whether CABG without cardiopulmonary bypass (off-pump CABG) is associated with lower operative mortality than the conventional on-cardiopulmonary bypass (on-pump) approach. METHODS: From October 1998 to June 2001, off-pump CABG was performed on 2477 patients and on-pump CABG was performed on 3077 patients. The patients undergoing off-pump CABG were randomly matched to on-pump patients via propensity score. Seventy-four percent of the off-pump CABG patients were matched with on-pump patients via propensity scores. A logistic regression model was used to test the difference in the postoperative mortality rate between off-pump CABG and on-pump CABG, controlling the correlation between matched sets. A multiple logistic regression model predicting the risk of mortality adjusted by risk factors of mortality and operation type was computed. RESULTS: Results from the general estimating equation showed that patients who had on-pump CABG were 1.6 (95% confidence intervals (CI)=1.2-2.0, P<0.01) times more likely to die during the first 30 days after surgery than patients who had off-pump CABG. Independent predictors of 30-day mortality identified from the multiple logistic model included on-pump CABG (versus off-pump CABG), advanced age, female gender, carotid artery disease, chronic renal failure, depressed ejection fraction, reoperative CABG, preoperative intraaortic balloon counterpulsation, and recent myocardial infarction. CONCLUSION: Excellent clinical results and a lower operative mortality rate can be achieved with the off-pump CABG technique compared with the conventional on-pump approach.