Risk score for predicting long-term mortality after coronary artery bypass graft surgery.

BACKGROUND: No simplified bedside risk scores have been created to predict long-term mortality after coronary artery bypass graft surgery. METHODS AND RESULTS: The New York State Cardiac Surgery Reporting System was used to identify 8597 patients who underwent isolated coronary artery bypass graft surgery in July through December 2000. The National Death Index was used to ascertain patients' vital statuses through December 31, 2007. A Cox proportional hazards model was fit to predict death after CABG surgery using preprocedural risk factors. Then, points were assigned to significant predictors of death on the basis of the values of their regression coefficients. For each possible point total, the predicted risks of death at years 1, 3, 5, and 7 were calculated. It was found that the 7-year mortality rate was 24.2 in the study population. Significant predictors of death included age, body mass index, ejection fraction, unstable hemodynamic state or shock, left main coronary artery disease, cerebrovascular disease, peripheral arterial disease, congestive heart failure, malignant ventricular arrhythmia, chronic obstructive pulmonary disease, diabetes mellitus, renal failure, and history of open heart surgery. The points assigned to these risk factors ranged from 1 to 7; possible point totals for each patient ranged from 0 to 28. The observed and predicted risks of death at years 1, 3, 5, and 7 across patient groups stratified by point totals were highly correlated. CONCLUSION: The simplified risk score accurately predicted the risk of mortality after coronary artery bypass graft surgery and can be used for informed consent and as an aid in determining treatment choice.

Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial.

CONTEXT: Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery bypass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery. OBJECTIVE: To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days. DESIGN, SETTING, AND PARTICIPANTS: The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010. INTERVENTIONS: Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction. MAIN OUTCOME MEASURE: Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28. RESULTS: Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured. CONCLUSION: In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00872001.

First Successful LVAD Implantation After BioVentrix Revivent TC Ventricular Reshaping.

The Revivent TC System (BioVentrix Inc, San Ramon, CA) enables a less invasive approach for left ventricular reshaping and scar exclusion in selected patients with ischemic cardiomyopathy. Although the system is designed to improve quality of life and to promote reverse remodeling, patients can still progress to end-stage heart failure requiring advanced therapies. This report describes a case of left ventricular assist device surgery in a patient 16 months after Revivent System implantation. The planning process and surgical technique proved to be complex. This case report can help provide guidance to advanced heart failure teams who encounter patients with the Revivent System who require left ventricular assist device support.

Pacing-induced cardiac gap junction remodeling: modulation of connexin43 phosphorylation state.

BACKGROUND: Altered myocardial distribution of gap junctions and intercellular coupling have been implicated in nonuniform conduction of the depolarization wave and repolarization asynchrony in the mammalian heart. We tested the hypothesis that short-term cardiac pacing is associated with structural remodeling of gap junctions and their altered spatial distribution in cardiac myocytes in the immediate vicinity of the pacing site. MATERIALS AND METHODS: Isolated adult male rat hearts (n = 8) were perfused using a Langendorff apparatus. A multimicroelectrode array pacing catheter was positioned in the endocardial apical region of the right ventricle. Pacing (330 bpm; stimulus: 1.5 V, 5 milliseconds) was applied for 3 hours. Immunoblotting and immunohistochemical assays [using serine specific (Ser368) anti-connexin43 and anti-phosphoserine antibody] were used to determine the phosphorylation state of connexin43 (Cx43) and to determine its spatial distribution. RESULTS: Pacing was associated with a consistent, increased dephosphorylation state of Cx43 at the pacing site when compared to remote regions. In control hearts, Cx43 manifested a predominantly phosphorylated state; Western blotting analysis showed that dephosphorylated Cx43 was more abundant (1.5 +/- 0.33-fold) in the paced hearts than in controls (P < 0.02). Global cardiac function parameters, such as developed left ventricular pressure and oxygen demand index (rate-pressure product), did not differ significantly in paced hearts compared with controls (P > 0.05). CONCLUSIONS: A relatively short period of cardiac asynchronous pacing is associated with remodeling of gap junctions as manifested in the altered phosphorylation state of their constituent Cx43. This effect is confined to the myocardial tissue surrounding the pacing electrodes and does not alter global cardiac mechanics and energetics. These results, considered together with the known involvement of Ser368 in the gating of Cx43 and the putative role of Cx43 in the intercellular conductance, suggest that pacing-induced localized gap junctional remodeling could contribute to the creation of a reentrant substrate.

Vascular lesions of the mediastinum.

Most mediastinal masses seen on thoracic imaging are of solid tumor origin. As such, vascular lesions of the mediastinum can be mistaken for, or misinterpreted as, one of these more common mediastinal masses. This article stresses the importance of considering vascular entities in the differential diagnosis of mediastinal masses.

Single versus multiple internal mammary artery grafting for coronary artery bypass: 15-year follow-up of a clinical practice trial.

BACKGROUND: The long-term clinical advantages of using routine multiple internal mammary artery (IMA) grafts for coronary artery bypass (CAB) are not clear. This study was designed to test the hypothesis that multiple IMA grafts would provide better 15-year outcomes when compared with single IMA and vein grafts. METHODS AND RESULTS: Between 1984 and 1987, 1067 consecutive patients undergoing isolated CAB were referred to 1 surgeon practicing primarily single and another surgeon maximizing multiple IMA grafts (clinical practice trial). A 207-patient subset with multiple IMAs underwent postoperative graft angiography at 1 to 32 weeks to define initial IMA patency. Patients were followed-up yearly, and the groups were analyzed as (I) surgical strategy (surgeon operating) (single=413 versus multiple=654), (II) ultimate operation performed (single=418 versus multiple=449), or (III) single versus multiple coronary systems revascularized with IMAs (single=490 versus multiple=377). Advantages of this study design were that an entire referral population was examined, multiple IMAs were applied to the entire spectrum of baseline patient risk, 15-year follow-up provided a complete prognostic picture, and the subgroups were potentially comparable at baseline. In all 3 analyses, single and multiple groups were statistically similar with respect to baseline, operative, and immediate postoperative variables. Early IMA patency was 98.5% (333/338 grafts patent), validating the quality of IMA procedures. Unadjusted and adjusted 15-year outcome analyses for I, II, and III for death, myocardial infarction, percutaneous coronary intervention, redo coronary bypass, and the composite of all events identified multiple versus single as a significant predictor of outcome for the composite end point in adjusted analysis III (hazard ratio=0.808; 95% CI, 0.689 to 0.948; P=0.009), because of a 5% to 10% absolute reduction in each of the outcome variables at 15 years. Moreover, >50% reduction in reoperation rate was observed at 15 years in every analysis. CONCLUSIONS: At 15-year follow-up, multiple IMA grafting was associated with a 19.2% adjusted risk reduction in death and cardiac events, caused by decreases in all adverse end points and fewer reoperations. These data indicate that the clinical advantages of maximizing IMA conduits are significant. Based on this information, it is suggested that multiple IMA grafting to 2 coronary systems should be applied liberally to patients with noncardiac risk profiles predictive of long-term survival.

Comparison of 3-Year Outcomes for Coronary Artery Bypass Graft Surgery and Drug-Eluting Stents: Does Sex Matter?

BACKGROUND: Several randomized controlled trials and observational studies have compared outcomes for coronary artery bypass graft (CABG) surgery and drug-eluting stents (DES), but these studies have not thoroughly investigated the relative difference in outcomes by sex. We aimed to compare 3-year outcomes (mortality, mortality/myocardial infarction/stroke, and repeat revascularization) for CABG surgery and percutaneous coronary interventions with DES by sex. METHODS: A total of 4,532 women (2,266 pairs of CABG and DES patients) and 11,768 men (5,884 pairs) were propensity matched separately using multiple patient risk factors and were compared with respect to 3-year outcomes. RESULTS: Both women and men receiving DES had significantly higher mortality rates (adjusted hazard ratio, 1.28; 95% confidence interval, 1.06 to 1.54 and adjusted hazard ratio, 1.22; 95% confidence interval, 1.06 to 1.41, respectively) and myocardial infarction/mortality/stroke rates (adjusted hazard ratio, 1.40; 95% confidence interval, 1.19 to 1.64 and adjusted hazard ratio, 1.36; 95% confidence interval, 1.20 to 1.54, respectively) with DES. The advantage for CABG surgery was also present for several preselected patient subgroups. Men had consistently lower adverse outcome rates than women for both procedures. For example, the mortality rates for CABG and DES for men were 8.0% and 9.1%, compared with respective rates of 11.8% and 13.7% for women. CONCLUSIONS: For women, the advantage of CABG surgery over DES is very similar to what was found for men, and this advantage persisted for patients with and without high-risk characteristics.

Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype.

BACKGROUND: Intercellular crosstalk and cellular plasticity are key factors in embryogenesis and organogenesis. The microenvironment plays a critical role in directing the progression of stem cells into differentiated cells. We hypothesized that intercellular interaction between adult human mesenchymal stem cells and adult human cardiomyocytes would induce stem cells to acquire the phenotypical characteristics of cardiomyocytes, and we tested the role that direct cell-to-cell contact plays in directing this differentiation process. Human mesenchymal stem cells were cultured in the presence of human cardiomyocytes ("coculture") or in the presence of media conditioned by separate cultures of human cardiomyocytes ("conditioned media"). METHODS: Human cardiomyocytes were labeled with chloromethyl derivatives of fluorescein diacetate. In the coculture experiments, human mesenchymal stem cells and human cardiomyocytes were mixed at a 1:1 ratio in smooth muscle 2 media and seeded at a cell density of 10,000 cells/cm(2). Cells were cocultured in an incubator at 37 degrees C for 48 hours. Subsequently, fluorescence-activated cell sorting was used to extract the differentiating human mesenchymal stem cells. In the conditioned media experiments, human mesenchymal stem cells were incubated in media previously conditioned by cardiomyocytes, in the presence and absence of serum (+/-serum). The conditioned media was changed 3 times, at intervals of 48 hours. Total RNA was isolated and reverse transcriptase-polymerase chain reaction was performed for expression of contractile proteins and cardiac specific genes. Immunostaining against myosin heavy chain, beta-actin troponin-T, and troponin-I was performed. RESULTS: Fluorescence-activated cell sorting analysis identified 66% of the human mesenchymal stem cells in the G1 phase. Differentiated hMSCs from the coculture experiments expressed myosin heavy chain, beta-actin, and troponin-T by reverse transcriptase-polymerase chain reaction. Immunostaining was also positive against myosin heavy chain and troponin-T. In contrast, only beta-actin expression was observed in the human mesenchymal stem cells incubated with conditioned media +/- serum. CONCLUSION: In addition to soluble signaling molecules, direct cell-to-cell contact is obligatory in relaying the external cues of the microenvironment controlling the differentiation of adult stem cells to cardiomyocytes. These data indicate that human mesenchymal stem cells are plastic and can be reprogrammed into a cardiomyogenic lineage that may be used in cell-based therapy for treating heart failure.

Central sympathetic blockade ameliorates brain death-induced cardiotoxicity and associated changes in myocardial gene expression.

OBJECTIVE: Brain death results in cardiac injury and hemodynamic instability. After brain death, catecholamine levels surge in concert with increased expression of select myocardial gene products. Sympathetic blockade was used to investigate the effects of the adrenergic nervous system on myocardial gene expression in a rabbit model of brain death. METHODS: A balloon expansion model of brain death in rabbits (n = 42) was used with and without sympathetic blockade (xylazine, acetylpromazine, and ketamine). Sham-operated and naive rabbits served as control animals. Over 4 hours, mean arterial pressure, heart rate, electrocardiographic results, catecholamine levels, myocardial histology, and messenger RNA levels were assessed. RESULTS: Sympathetic blockade decreased basal catecholamine levels and blocked the catecholamine surge accompanying brain death. The typical hemodynamic instability, adverse electrocardiographic changes, and myocellular injury associated with brain death were all significantly decreased. Sympathetic blockade not only suppressed the previously reported increases in myocardial gene expression (cardiac and skeletal alpha-actin, egr-1, and heat shock protein 70) but also suppressed the expression of multiple other genes (alpha and beta myosin heavy chain, calcium ATPase [sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase pump, SERCA-2a], phospholamban [ryanodine receptor], and c-jun). CONCLUSION: Central sympathetic blockade minimizes the hemodynamic instability associated with brain death and neutralizes the increased expression of multiple myocardial gene products associated with brain death.

Off-pump epicardial ventricular reconstruction restores left ventricular twist and reverses remodeling in an ovine anteroapical aneurysm model.

OBJECTIVE: The loss of normal apical rotation is associated with left ventricular (LV) remodeling and systolic dysfunction in patients with congestive heart failure after myocardial infarction. The objective of the present study was to evaluate the effect of epicardial ventricular reconstruction, an off-pump, less-invasive surgical reshaping technique, on myocardial strain, LV twist, and the potential alteration of myocardial fiber orientation in an ovine model of LV anteroapical aneurysm. METHODS: LV anteroapical myocardial infarction was induced by coil embolization of the left anterior descending artery. Eight weeks after occlusion, epicardial ventricular reconstruction was performed using left thoracotomy under fluoroscopic guidance in 8 sheep to completely exclude the scar. The peak systolic longitudinal/circumferential strains and LV twist were evaluated using speckle tracking echocardiography before (baseline), after device implantation, and at 6 weeks of follow-up. RESULTS: Epicardial ventricular reconstruction was completed in all sheep without any complications. Immediately after device implantation, LV twist significantly increased (4.18 ± 1.40 vs baseline 1.97 ± 1.92; P = .02). The ejection fraction had increased 17% and LV end-systolic volume had decreased 40%. The global longitudinal strain increased from -5.3% to -9.1% (P < .05). Circumferential strain increased in both middle and apical LV segments, with the greatest improvement in the inferior lateral wall (from -11.4% to -20.6%, P < .001). These effects were maintained ≥6 weeks after device implantation without redilation. CONCLUSIONS: Less invasive than alternative therapies, epicardial ventricular reconstruction on the off-pump beating heart can restore LV twist and systolic strain and reverse LV remodeling in an ovine anteroapical aneurysm model.

Predictors of contemporary coronary artery bypass grafting outcomes.

OBJECTIVES: The study objective was to identify the predictors of outcomes in a contemporary cohort of patients from the Reduction in cardiovascular Events by acaDesine in patients undergoing CABG (RED-CABG) trial. Despite the increasing risk profile of patients who undergo coronary artery bypass grafting, morbidity and mortality have remained low, and identification of the current predictors of adverse outcomes may permit new treatments to further improve outcomes. METHODS: The RED-CABG trial was a multicenter, randomized, double-blind, placebo-controlled study that determined that acadesine did not reduce adverse events in moderately high-risk patients undergoing nonemergency coronary artery bypass grafting. The primary efficacy end point was a composite of all-cause death, nonfatal stroke, or the need for mechanical support for severe left ventricular dysfunction through postoperative day 28. Logistic regression modeling with stepwise variable selection identified which prespecified baseline characteristics were associated with the primary outcome. A second logistic model included intraoperative variables as potential covariates. RESULTS: The 4 independent preoperative risk factors predictive of the composite end point were (1) a history of heart failure (odds ratio, 2.9); (2) increasing age (odds ratio, 1.033 per decade); (3) a history of peripheral vascular disease (odds ratio, 1.6); and (4) receiving aspirin before coronary artery bypass grafting (odds ratio, 0.5), which was protective. The duration of the cardiopulmonary bypass (odds ratio, 1.8) was the only intraoperative variable that contributed to adverse outcomes. CONCLUSIONS: Patients who had heart failure and preserved systolic function had a similar high risk of adverse outcomes as those with low ejection fractions, and new approaches may mitigate this risk. Recognition of patients with excessive atherosclerotic burden may permit perioperative interventions to improve their outcomes. The contemporary risks of coronary artery bypass grafting have changed, and their identification may permit new methods to improve outcomes.

Hot shot induction and reperfusion with a specific blocker of the es-ENT1 nucleoside transporter before and after hypothermic cardioplegia abolishes myocardial stunning in acutely ischemic hearts despite metabolic derangement: hot shot drug delivery before hypothermic cardioplegia.

OBJECTIVE: Simultaneous inhibition of the cardiac equilibrative-p-nitrobenzylthioinosine (NBMPR)-sensitive (es) type of the equilibrative nucleoside transport 1 (ENT1) nucleoside transporter, with NBMPR, and adenosine deaminase, with erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA), prevents release of myocardial purines and attenuates myocardial stunning and fibrillation in canine models of warm ischemia and reperfusion. It is not known whether prolonged administration of hypothermic cardioplegia influences purine release and EHNA/NBMPR-mediated cardioprotection in acutely ischemic hearts. METHODS: Anesthetized dogs (n = 46), which underwent normothermic aortic crossclamping for 20 minutes on-pump, were divided to determine (1) purine release with induction of intermittent antegrade or continuous retrograde hypothermic cardioplegia and reperfusion, (2) the effects of postischemic treatment with 100 µM EHNA and 25 µM NBMPR on purine release and global functional recovery, and (3) whether a hot shot and reperfusion with EHNA/NBMPR inhibits purine release and attenuates ventricular dysfunction of ischemic hearts. Myocardial biopsies and coronary sinus effluents were obtained and analyzed using high-performance liquid chromatography. RESULTS: Warm ischemia depleted myocardial adenosine triphosphate and elevated purines (ie, inosine > adenosine) as markers of ischemia. Induction of intermittent antegrade or continuous retrograde hypothermic (4°C) cardioplegia releases purines until the heart becomes cold (<20°C). During reperfusion, the levels of hypoxanthine and xanthine (free radical substrates) were >90% of purines in coronary sinus effluent. Reperfusion with EHNA/NBMPR abolished ventricular dysfunction in acutely ischemic hearts with and without a hot shot and hypothermic cardioplegic arrest. CONCLUSIONS: Induction of hypothermic cardioplegia releases purines from ischemic hearts until they become cold, whereas reperfusion induces massive purine release and myocardial stunning. Inhibition of cardiac es-ENT1 nucleoside transporter abolishes postischemic reperfusion injury in warm and cold cardiac surgery.

Durability of epicardial ventricular restoration without ventriculotomy.

OBJECTIVES: We previously presented early results employing a technique designed for beating heart, ventricular volume reduction (surgical ventricular restoration, SVR) without ventriculotomy for patients with antero-septal scar and dilated ischaemic cardiomyopathy. Significant volume reduction and clinical improvement were achieved. We now report durability in the first 11 patients available for assessment at 6 and 12 months after operation. METHODS: After the Ethics Committee approval, 31 symptomatic patients with left ventricular (LV) dilatation and antero-septal scars underwent operation. The scarred lateral LV wall was apposed to the septal scar with serial paired anchors placed through epicardial transmural catheters, excluding non-viable portions of the chamber. Patients were followed at 1, 3, 6 and 12 months postoperatively with echocardiograms. Data are presented for the first 11 patients for whom core lab echocardiographic data were available at 12 months of follow-up. RESULTS: LV end-systolic index (LVESVI), percent decreases from baseline at 6 and 12 months were 36.2 ± 18.3 (P < 0.001) and 39.6 ± 14.8 (P < 0.001). LV end-diastolic volume index (LVEDVI) percent decreases from baseline at 6 and 12 months were 28.6 ± 18.8 (P < 0.001) at 6 months and 32.2 ± 14.9 (P < 0.005) at 12 months. All comparisons were by one-tailed t-tests using paired data. CONCLUSIONS: These results demonstrate the persistence of volume reduction employing a technique designed to be used on beating hearts without ventriculotomy or cardiopulmonary bypass. The extent of volume reduction was consistent with results of conventional SVR in experienced centres. These early data validate the further development of technical iterations leading to a clinical study employing a closed chest endovascular platform.

Epicardial catheter-based ventricular reconstruction: a novel therapy for ischaemic heart failure with anteroapical aneurysm.

OBJECTIVES: Surgical ventricular reconstruction has been used to treat ischaemic cardiomyopathy with large akinetic or dyskinetic areas. However, application of this approach requires a sternotomy, cardiopulmonary bypass and a left ventriculotomy. This study assessed the feasibility and efficacy of minimally invasive, off-pump, epicardial catheter-based ventricular reconstruction (ECVR) in an anteroapical aneurysm ovine model. METHODS: Left ventricular (LV) anteroapical myocardial infarction was induced percutaneously by coil embolization of the left anterior descending coronary artery. Eight weeks after infarction, via mini left thoracotomy and without cardiopulmonary bypass, ECVR was performed in six sheep. The scar was excluded by placing anchor pairs on the LV epicardial anterior wall and the right ventricular side of the interventricular septum under fluoroscopic guidance. LV performance was evaluated before, immediately after device implantation and after 6 weeks by echocardiography. Terminal histopathology was performed. RESULTS: ECVR was completed expeditiously in all animals without complications. Parameters obtained 6 weeks after device implantation were compared with baseline (pre-device). End-systolic volume was decreased by 38% (25.6 ± 6.1 ml vs baseline 41.2 ± 7.2 ml, P = 0.02) with preservation of stroke volume. Ejection fraction was significantly increased by 13% (48.5 ± 7% vs baseline 35.8 ± 7%, P = 0.02). The circumferential strain in the anterior septum (-7.67 ± 5.12% vs baseline -0.96 ± 2.22%, P = 0.03) and anterior wall (-9.01 ± 3.51% vs baseline -4.15 ± 1.36%, P = 0.01) were significantly improved. The longitudinal strain in apex was reversed (-3.08 ± 1.53% vs baseline 3.09 ± 3.39%, P = 0.01). Histopathology showed full endocardial healing over the anchors with appreciable reduction of the chronic infarct in the LV. CONCLUSIONS: ECVR without cardiopulmonary bypass is a less invasive alternative to current standard therapies, reverses LV remodelling and improves cardiac performance in an ovine model of anteroapical aneurysm.

Long-term mortality of coronary artery bypass graft surgery and stenting with drug-eluting stents.

BACKGROUND: Few studies have examined differences in long-term mortality between coronary artery bypass graft surgery and stenting with drug-eluting stents (DES) for multivessel disease without left main coronary artery stenosis. This study compares the risks of long-term mortality between these 2 procedures during a follow-up of up to 5 years. METHODS: Patients who underwent isolated bypass surgery (n=13,212) and stenting with DES (n=20,161) between October 2003 and December 2005 in New York State were followed for their vital status through 2008. To control for treatment selection bias, bypass and stenting patients were matched on age, number of diseased coronary vessels, presence of proximal or nonproximal left anterior descending (LAD) artery disease, and propensity of undergoing bypass surgery. Five-year survival rates for the 2 procedures were compared and hazard ratios for death of bypass surgery compared with stenting were obtained. RESULTS: The respective 5-year survival rates in the 8,121 pairs of matched bypass and stenting patients were 80.4% and 73.6% (p<0.001), and the risk of death after bypass surgery was 29% lower than for stenting (hazard ratio = 0.71, 95% confidence interval: 0.67 to 0.77, p<0.001). Significantly lower risks of death for bypass surgery were observed in patients with LAD artery disease but not in patients without LAD artery disease. Significantly lower risks of death for bypass surgery were also found in all patient subgroups defined by the presence of selected baseline risk factors. CONCLUSIONS: Bypass surgery is associated with lower risk of death than stenting with DES for multivessel disease without left main stenosis.

On-pump inhibition of es-ENT1 nucleoside transporter and adenosine deaminase during aortic crossclamping entraps intracellular adenosine and protects against reperfusion injury: role of adenosine A1 receptor.

OBJECTIVE: The inhibition of adenosine deaminase with erythro-9 (2-hydroxy-3-nonyl)-adenine (EHNA) and the es-ENT1 transporter with p-nitro-benzylthioinosine (NBMPR), entraps myocardial intracellular adenosine during on-pump warm aortic crossclamping, leading to a complete recovery of cardiac function and adenosine triphosphate (ATP) during reperfusion. The differential role of entrapped intracellular and circulating adenosine in EHNA/NBMPR-mediated protection is unknown. Selective (8-cyclopentyl-1,3-dipropyl-xanthine) or nonselective [8-(p-sulfophenyl)theophyline] A1 receptor antagonists were used to block adenosine A1-receptor contribution in EHNA/NBMPR-mediated cardiac recovery. METHODS: Anesthetized dogs (n = 45), instrumented to measure heart performance using sonomicrometry, were subjected to 30 minutes of warm aortic crossclamping and 60 minutes of reperfusion. Three boluses of the vehicle (series A) or 100 µM EHNA and 25 µM NBMPR (series B) were infused into the pump at baseline, before ischemia and before reperfusion. 8-Cyclopentyl-1,3-dipropyl-xanthine (10 µM) or 8-(p-sulfophenyl)theophyline (100 µM) was intra-aortically infused immediately after aortic crossclamping distal to the clamp in series A and series B. The ATP pool and nicotinamide adenine dinucleotide was determined using high-performance liquid chromatography. RESULTS: Ischemia depleted ATP in all groups by 50%. The adenosine/inosine ratios were more than 10-fold greater in series B than in series A (P < .001). ATP and function recovered in the EHNA/NBMPR-treated group (P < .05 vs control group). 8-Cyclopentyl-1,3-dipropyl-xanthine and 8-(p-sulfophenyl)theophyline partially reduced cardiac function in series A and B to the same degree but did not abolish the EHNA/NBMPR-mediated protection in series B. CONCLUSIONS: In addition to the cardioprotection mediated by activation of the adenosine receptors by extracellular adenosine, EHNA/NBMPR entrapment of intracellular adenosine provided a significant component of myocardial protection despite adenosine A1 receptor blockade.

Myocardial protection in beating heart cardiac surgery: I: pre- or postconditioning with inhibition of es-ENT1 nucleoside transporter and adenosine deaminase attenuates post-MI reperfusion-mediated ventricular fibrillation and regional contractile dysfunction.

OBJECTIVE: To determine the role of the p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 (es-ENT1) in postmyocardial infarction reperfusion injury-mediated ventricular fibrillation and regional dysfunction. We used erythro-9 (2-hydroxy-3-nonyl)-adenine and p-nitrobenzylthioinosine to inhibit both adenosine deamination and transport in a canine model of off pump acute myocardial infarction. METHODS: Anesthetized adult dogs (n = 37), instrumented to monitor the percentage of systolic segmental shortening and wall thickening using sonomicrometry, underwent 90 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion. Myocardial coronary blood flow, adenosine triphosphate pool, infarct size, and the incident of ventricular fibrillation and cardioversion were also measured. The dogs received an intravenous infusion of the vehicle (control) or 100 µM of erythro-9 (2-hydroxy-3-nonyl)-adenine and 25 µM p-nitrobenzylthioinosine before ischemia (preconditioning group) or just before reperfusion (postconditioning group). RESULTS: In the control group, adenosine triphosphate depletion was associated with the accumulation of more inosine than adenosine during ischemia and washed out during reperfusion. Myocardial adenosine and inosine were the major nucleosides in the pre- and postconditioning groups during ischemia and remained detectable during reperfusion. In both groups, recovery of systolic segmental shortening and wall thickening and a reduction in the incidence of ventricular fibrillation (P < .05 vs the control group) coincided with retention of myocardial nucleosides. The infarct size in the 3 groups was not significantly different, independent of myocardial blood flow during ischemia. CONCLUSIONS: Preconditioning or postconditioning with erythro-9 (2-hydroxy-3-nonyl)-adenine/p-nitrobenzylthioinosine significantly reduced the incidence of ventricular fibrillation and cardioversion and attenuated regional contractile dysfunction mediated by postmyocardial infarction reperfusion injury. It is concluded that p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 played a major role in these events.

A comparison of long-term mortality for off-pump and on-pump coronary artery bypass graft surgery.

BACKGROUND: The survival difference between off-pump and on-pump coronary artery bypass graft surgery for follow-up longer than 5 years is not well-understood. The objective of this study is to examine the difference in 7-year mortality after these 2 procedures. METHODS AND RESULTS: The state of New York's Cardiac Surgery Reporting System was used to identify the 2640 off-pump and 5940 on-pump patients discharged from July through December 2000. The National Death Index was used to ascertain patients' vital statuses through 2007. A logistic regression model was fit to predict the probability of receiving an off-pump procedure using baseline patient characteristics. Off-pump and on-pump patients were matched with a 1:1 ratio based on the probability of receiving an off-pump procedure. Kaplan-Meier survival curves for the 2 procedures were compared using the propensity-matched data, and the hazard ratio for death for off-pump in comparison with on-pump procedures was obtained. In subgroup analyses, the significance of interactions between type of surgery and baseline risk factors was tested. In this study, 2631 pairs of off-pump and on-pump patients were propensity matched. The 7-year Kaplan-Meier survival rates were 71.2% and 73.4% (P=0.07) for off-pump and on-pump surgery, respectively. The hazard ratio for death (off-pump versus on-pump) was 1.10 (95% confidence interval: 0.99 to 1.21, P=0.07). No statistical significance was detected for the interaction terms between the type of surgery and a number of different baseline risk factors. CONCLUSIONS: The difference in long-term mortality between on-pump and off-pump coronary artery bypass graft surgery is not statistically significant.