The Year in Cardiovascular Surgery

Transcription

1 Journal of the American College of Cardiology Vol. 45, No. 9, by the American College of Cardiology Foundation ISSN /05/$30.00 Published by Elsevier Inc. doi: /j.jacc YEAR IN CARDIOLOGY SERIES The Year in Cardiovascular Surgery Robert H. Jones, MD, FACC Durham, North Carolina This paper highlights information from cardiovascular surgery articles published in 2004 that are likely to have a broad impact on the practice of cardiovascular specialists in the years ahead. A scan of major general and cardiovascular journals, complemented by a formal MEDLINE search, focused on identifying well-conducted randomized or observational studies of clinical outcomes that should inform cardiovascular surgery care management decisions for individual patients with specific cardiovascular disease presentations. Articles intentionally avoided were those describing promising but undocumented technology as well as articles detailing failure of previously promising but now less attractive surgical techniques. Preference has been given to reporting articles that are fresh in vision, thoughtful in design, and definitive in conclusions. QUALITY OF CARDIOVASCULAR SURGICAL CARE Cardiovascular surgery databases. In 1989, the Society of Thoracic Surgeons (STS) created a voluntary database that continues as the most effective effort among cardiovascular professional organizations to support quality improvement (1). Clinical information related to 2,164,079 surgical procedures from 70% of hospitals currently performing heart surgery in the U.S. serves as a national resource for benchmarking cardiac surgery patient outcomes that also may be used to track national trends of change over time (Table 1). Patients undergoing a coronary artery bypass grafting (CABG) operation in 2000 to 2003 were heavier in weight and had greater incidences of diabetes and cerebrovascular disease than those undergoing this procedure in 1995 to 1999 (Table 2). Increased preoperative severity of illness appeared responsible for more blood transfusions, longer postoperative ventilator use, and more hospital readmissions within 30 days after discharge in the 2000 to 2003 compared with the 1995 to 1999 patient cohort (Table 3). Multivariable algorithms developed from the total population predicted an increased risk of death, morbidity, and other complications in this 2000 to 2003 patient cohort because of greater severity of disease at baseline (Table 4). The degree of agreement in numbers of CABG operations and deaths reported in the Medicare Provider and Analysis Review (MEDPAR) and STS datasets suggests that under-reporting of unfavorable outcomes in the STS From the Department of Surgery/Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. Manuscript received February 2, 2005; revised manuscript received February 25, 2005, accepted March 1, database is not a major concern. Table 5 shows the STS to be a more inclusive dataset than MEDPAR. This observation is explained in part by the MEDPAR policies of omitting patients enrolled in health maintenance organizations and categorizing CABG combined with other procedures separately from CABG. The STS policy of including CABG with and without associated procedures may explain the higher rate of mortality in the more-inclusive STS dataset. Overall, these comparisons suggest there is no systemic under-reporting of deaths in the STS database. The STS has encouraged point of entry data quality controls with immediate internal auditing for data consistency to assess data quality in this voluntary system. The question of whether unaudited records from the STS database were accurate was directly addressed in an audit of 10% of records of an annual experience at one institution (2). Discrepancies were noted in 5% or less of the more than 15 audited fields for 98.8% of records. Among the 32 variables used in mortality risk algorithms, discrepancies were present in 10% of audits on 30 of the 32 variables. This audit of a single site suggests that well-motivated sites can provide consistently high-quality data. However, it does not address the issue of the occurrence of selective reporting or upcoding of baseline variables at sites in which concern about surgical performance might foster an overstating of preoperative risk. Use of cardiovascular databases to improve quality of care of cardiovascular surgery. The most common use of large cardiovascular databases has been to compare risk-adjusted expected with observed mortality to monitor the quality of care of institutions and their providers. Database information also can be interrogated for opportunities for improvement in management decisions on individual patients or patient groups. For example, the accurate prediction of the likelihood that patients who present with unstable angina will subsequently undergo CABG might guide a physician as to the proper use of antiplatelet agents early on admission. To address this question, the Thrombolysis In Myocardial Infarction (TIMI)-18 database of 2,220 patients was used to derive an average likelihood score that was prospectively validated on 3,318 patients in the TIMI-IIB and TIMI-III registries (3). Multivariable analysis identified six variables that, when reduced to a simplified risk score, separated patients with a low, intermediate, or high probability of undergoing CABG during operation (Table 6). This risk score operated in the test population with a C statistic of A more accurate prediction of the likeli-

2 1518 Jones JACC Vol. 45, No. 9, 2005 Year in Cardiovascular Surgery May 3, 2005: Table 1. STS Database Summary for All Adult Cardiac Operations Variable Number of records 946, ,987 Age (yrs) Male (%) Weight (kg) Diabetes (%) Peripheral vascular disease (%) Cerebrovascular disease (%) Blood transfusion (%) Ventilator hours Postoperative LOS (days) Readmission 30 days (%) Source: LOS length of stay; STS Society of Thoracic Surgeons. Table 2. STS Database Baseline Characteristics for Patients Undergoing CABG Operations Variable Number of records 793, ,586 Age (yrs) Male (%) Ejection fraction Total ICU hours NA 51.2 Weight (kg) Diabetes (%) Peripheral vascular disease (%) Cerebrovascular disease (%) Previous other cardiac (PCI) (%) Meds-antiplatelets (%) NA 23.6 Source: CABG coronary artery bypass graft; ICU intensive care unit; PCI percutaneous coronary intervention; STS Society of Thoracic Surgeons. Table 3. STS Database Operative Outcomes Variable Blood products (%) Total hours ventilated Postoperative LOS Operative mortality (%) Mortality, % cardiac cause Readmission 30 days (%) Source: Abbreviations as in Table 1. hood of subsequent CABG at the time of diagnosis of acute coronary syndrome would permit cardiologists to better balance the potential benefit of clopidogrel with the risk of increasing postoperative bleeding when making a decision with an individual patient. The risk-adjusted mortality rate of each surgeon reporting data to the New York State Cardiovascular Database has been used to evaluate the influence of patient race on their access to a high-quality surgeon to perform their CABG (4). After controlling for patient characteristics, such as comorbidity and socioeconomic status, the hospital in which surgery was performed, and the number of surgeries performed by the surgeon during a three-month period, non- Caucasian patients were treated by surgeons with higher risk-adjusted mortality rates compared with Caucasian patients. Documentation of this modest, but important, absolute mortality difference of 0.17% (p 0.01) in operative mortality between non-caucasian and Caucasian patients required use of a geographic-based source of high-quality data. This resource also provides a mechanism to monitor the effectiveness of initiatives implemented to reduce the disparity in the access of minorities to high-quality cardiac surgeons. The objective for all patients to have access to highquality surgical care conflicts with the reality that in geographic regions with a low population density, cardiac surgical teams often do not attain the high volume necessary to maintain low rates of cardiac surgical mortality. Preferential referral of only high-risk patients to more remote high-volume centers while providing cardiac surgical care to the low-risk population locally has been evaluated as a strategy to balance access with quality using data from the New York State Cardiac Surgery Reporting System (5). The overall mortality of 57,150 patients undergoing isolated CABG surgery in New York State between 1997 and 1999 was 2.2%. Therefore, patients with a predicted mortality of 2% were defined as low risk and those with mortality greater than this threshold were defined as moderate- to high-risk patients. A total of 312 (0.79%) patients died among 39,491 low-risk patients who comprised 69% of all isolated CABG cases, and 948 patients (5.37%) died among 17,659 patients with moderate-to-high risk. In all five groupings of New York hospitals by the median annual hospital volumes created by the thresholds set at 100 operation increments between 200 and 600 operations, the risk reduction for undergoing CABG in a high-volume hospital ranged from 0.45 to 0.77 compared with the low-risk group and from 0.62 to 0.91 for the moderate- to high-risk group. The percentage of deaths that were avoidable decreased for both risk groups as the volume threshold increased but was always higher for the low-risk group (Fig. 1). The number needed to treat to avoid one death in the low-risk group ranged from 114 to 446 and always exceeded the number needed to treat to avoid one death in the moderate- to high-risk group, which ranged from 37 to 184 (Fig. 2). At all individual annual surgeon volume thresholds between 50 and 150, adjusted odds ratios comparing high- to low-volume individual surgeon mortality ranged from 0.43 to 0.47 for the low-risk group and from 0.79 to 0.86 for the Table 4. STS Database Multivariate Prediction of Risk Variable Mortality (%) Deep sternal wound infection (%) Reoperation (%) Permanent stroke (%) Prolonged ventilation (%) Renal failure (%) Morbidity or mortality (%) Source: STS Society of Thoracic Surgeons.

3 JACC Vol. 45, No. 9, 2005 May 3, 2005: Jones Year in Cardiovascular Surgery 1519 Table 5. Comparison of Hospital CABG Volume and In-Hospital Mortality in the STS and Medicare Datasets Number of hospitals Medicare volume 43,342 60,304 72,845 76,170 73,587 61,675 STS volume 46,247 63,594 79,597 85,043 85,868 74,906 Medicare deaths 1,624 2,173 2,616 2,631 2,466 2,101 STS deaths 2,050 2,597 3,217 3,328 3,229 2,899 Medicare mortality (%) STS mortality (%) Source: Welke KF, et al., Ann Thorac Surg 2004;77: Abbreviations as in Table 2. moderate- to high-risk group. Subsetting by the surgeon and hospital volume showed only a significantly greater chance of death when low-risk patients were treated at low-volume hospitals by low-volume surgeons. In the moderate- to high-risk group, only patients treated by a high-volume surgeon in a high-volume hospital had a significant reduction in death. For the purposes of healthcare planning, these data support policies that encourage the creation of cardiac surgery centers that perform at least 600 CABG operations annually that also are staffed with a sufficiently small number of cardiac surgeons to permit each to achieve a case volume exceeding 125 CABG operations annually. For guiding optimal management decisions in individual patients, these data support the referral of all high-risk patients to highvolume surgeons in high-volume centers. Patients with a low predictive CABG operative risk appear to be protected from the increase in risk incurred by undergoing operation at a low-volume hospital as long as they are under the care of a high-volume cardiac surgeon. However, because of the lower density of expected deaths in the low-risk population referred, it becomes impossible for individual cardiologists to assess significant differences among surgical providers for low-risk patients. Therefore, it is the responsibility of every cardiac surgery center and every cardiac surgeon, but especially those with low case volumes, to prospectively monitor and report cardiac surgical mortality using standardized methodology. SURGERY FOR CORONARY ARTERY DISEASE (CAD) Outcome comparison of CABG with alternate therapies. The question of whether percutaneous coronary intervention (PCI) or CABG offers an advantage over medical therapy (MED) in patients with stable angina and multivessel disease was addressed in the Medicine, Angioplasty, or Surgery Study (MASS-II) (6). This single-center trial identified 2,077 patients who were considered eligible for either CABG or PCI and randomized 611 patients to CABG (n 203), PCI (n 205), or MED (n 203) who met the entry criteria of angiographically documented proximal multivessel CAD, stable angina, or stress-induced ischemia. Patients were followed for a minimum of one year and a maximum of six years for the combined primary end point of cardiac mortality, myocardial infarction, or refractory angina requiring revascularization. Patients assigned to the PCI group had more events (n 50) than did patients receiving MED (n 29) or CABG (n 13). The cumulative cardiac-related mortality did not differ among the three therapeutic strategies (Fig. 3). The greatest difference among the three groups was the frequency of additional interventions (PCI or CABG) required during the year of follow-up, which was 25 for the PCI group, 16 for the medical group, and 1 for the CABG group (Fig. 4). This randomized trial has addressed a long-overlooked question about the relative value of revascularization compared with continued MED in patients with stable CAD and preserved left ventricular function. In the 25-year interval since this question has been addressed in a randomized trial, modern MED has evolved to offer patients a survival rate that is much higher than their natural history of disease that was the comparison called MED in earlier randomized trials. Because the maximal survival benefit of revascularization is limited by the number of deaths with MED, improvements in MED lower the opportunity for any revascularization therapy to enhance survival. Although the small numbers of events limit definitive conclusions, this study supports a patient-management strategy that takes time to maximize MED in patients with stable CAD and reserves revascularization options for signs of treatment failure. This first randomized trial of MED in multivessel patients eligible for revascularization by either CABG or PCI showed only modest symptomatic benefit of revascularization over MED. Compared with the MED group, PCI resulted in 34 more patients who were angina free at one year; however, nine more patients required repeat Table 6. Prediction of CABG in Patients With Unstable Angina Parameter Points Prior CABG 2 Positive troponin 3 Prior angina 1 ST-segment duration 0.05 m 1 Peripheral artery disease 1 Male 1 Total points CABG during hospitalization 6% 22% 55% CABG coronary artery bypass graft.

4 1520 Jones JACC Vol. 45, No. 9, 2005 Year in Cardiovascular Surgery May 3, 2005: Figure 1. Percentage of deaths avoidable if applying hospital volume-based referral for low- and moderate- to high-risk groups. Reprinted with permission from Wu et al. (5). angioplasty because of unstable angina. In contrast, the CABG group had 33 more patients that were angina free at one year and 15 fewer additional interventions than did the medical treatment group. The use of CABG resulted in more symptom- and event-free results than either PCI or MED. Three-year follow-up of the 1,205 patients with multivessel disease randomly assigned to PCI or CABG in the Arterial Revascularization Therapy Study (ARTS) (7) shows equivalent three-year survival rates without stroke or myocardial infarction for both treatments. Because PCIassigned patients undergo more repeat procedures than those assigned randomly to CABG, the earlier greater cost of CABG of 19,257 euros ($25,600) has decreased to 10,492 euros ($14,000). Diabetes (p ) and maximal pressure for stent deployment (p 0.002) were the strongest independent predictors of events at three years after PCI. Left anterior descending (LAD) coronary artery grafting was the best predictor of event-free survival after CABG (p 0.002). The assumption that CABG causes a decline in neurologic and cognitive function has been based on studies without controlled observations. A prospectively designed substudy of 153 of the 988 total patients in the Stent or Surgery Trial (SoS) evaluated neurologic and cognitive function by a battery of five neuropsychologic examinations at baseline, 6 months, and 12 months (8). No difference was observed at any time interval for any of the five tests between the 77 patients undergoing PCI or 68 patients undergoing CABG. The absence of significant cognitive decline after the procedure in either group and lack of difference between CABG and PCI argue for caution in drawing any guidelines for clinical practice from uncontrolled observations of cognitive decline. Graft patency. The long-term patency of saphenous vein and left internal thoracic artery (LITA) grafts recently was Figure 2. The number needed to treat (NNT) by higher-volume hospitals to avoid one death if applying hospital volume-based referral for low- and moderate- to high-risk groups. Reprinted with permission from Wu et al. (5).

5 JACC Vol. 45, No. 9, 2005 May 3, 2005: Jones Year in Cardiovascular Surgery 1521 Figure 3. Probability of survival free of cardiac-related mortality among Medicine, Angioplasty, or Surgery Study (MASS-II) patients in the three treatment groups with medical therapy (MT), coronary artery bypass grafting (CABG), or percutaneous coronary intervention (PCI). Reprinted with permission from Hueb et al. (6). assessed in a population of 1,254 patients who had been participants in one of two Veterans Affairs cooperative trials conducted in the 1980s to examine the effect of antiplatelet agents on graft patency by postoperative angiography at one week and one year after CABG (9). At least one postoperative cardiac catheterization occurred in 1,079 (86%) of the 1,254 patients. All but 5 of these 1,079 patients had one or more saphenous vein grafts, and 457 patients had a LITA graft. Therefore, patency rates must be considered in context of a 36% LITA graft use that most likely occurred to coronary arteries more suitable for grafting than those chosen for grafting with veins. The overall 10-year patency rate was 61% for saphenous vein grafts and 85% for LITA grafts (Fig. 5). If a vein graft was patent at the 1-week study, the 6-year patency rate was 76% and the 10-year patency rate was 68%. If a LITA graft was patent at 1 week, the 6-year and 10-year patency rates were 90% and 80%, respectively. Therefore, both LITA and vein grafts that were patent at six years had a similar modest occlusion rate over the subsequent four years. At 10 years, vein graft patency to the LAD coronary artery (69%) was better (p 0.001) than vein graft patency to the right coronary artery Figure 4. Probability of survival free of cardiac mortality, unstable angina requiring revascularization, and myocardial infarction among patients in the three treatment groups: medical therapy (MT), coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI). Reprinted with permission from Hueb et al. (6).

6 1522 Jones JACC Vol. 45, No. 9, 2005 Year in Cardiovascular Surgery May 3, 2005: Figure 5. Plot of time-related graft patency (or freedom from graft occlusion) for saphenous vein grafts (SVG) and internal mammary artery (IMA) grafts. The number of patients at each time point is listed. *p (IMA vs. SVG). CABG coronary artery bypass grafting. Reprinted with permission from Goldman et al. (9). (56%) or circumflex coronary artery (58%) (Fig. 6). Left internal thoracic artery grafts to the LAD had a higher patency than single saphenous vein grafts to the LAD, 89% versus 69% (p 0.001). Along with LAD as the distal site, the best predictor of graft patency during the 10-year period after bypass was the diameter of the recipient vessel. The 10-year patency rate was 88% in vessels 2 mm compared with 55% in vessels with diameters 2 mm(p 0.001). The 10-year patency rate of conduits to an LAD 2 mm was 90% for saphenous vein grafts and 100% for LITA grafts. In contrast, the patency rate for conduits to LADs Figure 6. Plot of time-related graft patency (or freedom from graft occlusion) for saphenous vein grafts (SVG) to the left anterior descending (LAD), circumflex (CX), and right coronary (RCA) arteries. The number of patients at each time point is listed. *p (LAD vs. CX and/or RCA). CABG coronary artery bypass grafting. Reprinted with permission from Goldman et al. (9). with 2 mm diameter was 52% for saphenous vein grafts and 82% for LITA grafts. Other positive significant predictors of graft patency during the 10-year period after bypass were older age, use of aspirin after CABG, lower serum cholesterol, and Canadian Cardiovascular Society (CCS) angina class I. The presence of diabetes and cigarette smoking did not predict graft patency. These data argue for more selectivity in choosing to graft borderline coronary arteries and for intensive risk factor modification in all patients undergoing CABG. A subgroup of 407 of the 1,829 patients entered into the Bypass Angioplasty Revascularization Investigation (BARI) underwent a 5-year angiogram as part of an ancillary study (Fig. 7) (10). Their myocardial jeopardy index for ischemia fell from 60% at baseline to 17% for PCI patients and 7% for CABG patients one year after randomization to treatment. At the 5-year assessment, the myocardial jeopardy index increased to 25% for patients undergoing PCI and 20% for patients undergoing CABG, but intercurrent revascularization procedures had occurred in 53% of patients assigned to PCI compared with 8% of patients assigned to CABG. Disease progression, not revascularization failure, was the most common cause of increased jeopardy in both populations. Lipid-lowering drugs were used at baseline in only 5% of patients, and by the time of five-year follow-up, only 44% of patients were on lipid-lowering medications. Comparison of outcomes for CABG procedures performed on and off cardiopulmonary bypass. A metaanalysis of data from 18 randomized trials published before August 2003 assessed the combined postoperative end point of mortality, stroke, and myocardial infarction in 1,584 patients, of which 783 were randomized to off-pump and 801 to on-pump coronary surgery (11). Compared with on-pump CABG, off-pump CABG reduced the relative risk of the combined end point by 27% at 2 weeks, 25% at 1 month, 45% at 3 months, and 34% at 1 year. However, the absolute numbers of events was sufficiently small enough so that none of these differences reached statistical significance. In 2004, five additional randomized trials reported shortterm outcomes in an additional 1,164 patients. The combined end point of death, stroke, or myocardial infarction occurred in 17 (2.9%) of 580 on-pump and 23 (3.9%) of 584 off-pump CABG operations (12 16). Surviving patients from three of these studies underwent subsequent angiographic assessment. In one study, a oneyear follow-up coronary angiography in 255 patients of 400 randomized patients showed excellent and equivalent patency of arterial grafts in both the on- and off-pump cohorts (17). However, coronary bypass grafts constructed with a saphenous vein showed an unusually low one-year patency in both groups that was 59% for on-pump and 49% for off-pump CABG. The reason for this uncharacteristically low patency rate for the entire cohort is unclear and limits the generalizability of this study. More generalizable graft patency data were reported for an 82-patient subgroup of a 104-patient randomized trial in which patients were studied

7 JACC Vol. 45, No. 9, 2005 May 3, 2005: Jones Year in Cardiovascular Surgery 1523 Figure 7. (A) The distribution of myocardial jeopardy scores at baseline, one-year, and five-year angiography among the subset of 183 patients with baseline, one-year, and five-year angiographic assessments. The center block on each vertical line depicts the mean myocardial jeopardy; the horizontal hash marks at each end of the vertical line represent myocardial jeopardy scores at 1 SD from the mean. The n values for the percutaneous coronary intervention (PCI) group reflect not having undergone previous coronary artery bypass grafting (CABG) surgery at each follow-up assessment. Reprinted with permission from Alderman et al. (10). by coronary angiography three months postoperatively (15) and for a 153-patient subgroup of 200 randomized patients studied by coronary angiography at one year in another study (16). The overall graft patency rate was higher when CABG was performed using cardiopulmonary bypass in both studies, but this difference was only statistically significant in the study reporting patency at three months. Combining patency data for all conduits from both studies showed 249 (95.8%) of 260 grafts constructed on-pump to be patent compared with 235 (93.6%) of 251 grafts that remained patent in off-pump patients. The evolving information on short-term outcomes shows no consistent advantage to support the routine use of off-pump CABG as standard surgical revascularization therapy. However, on-pump CABG appears sufficiently safe to justify its use in selected patients, such as patients with extensive atherosclerosis in whom it may be difficult or unsafe to establish arterial inflow needed for cardiopulmonary bypass. However, equivalent short-term outcomes must be accompanied by convincing information that documents constructing anastomoses on the beating heart inflicts no long-term detriment in survival or increased need for repeat procedures. The most substantial data now available on short- and long-term comparative outcomes of on- and off-pump coronary bypass have been reported from the New York State Cardiac Reporting System (18). In-hospital mortality and complications and three-year mortality and revascularization were compared in 9,135 off-pump CABG patients and 59,044 on-pump CABG patients undergoing operation during 1997 to Risk-adjusted inpatient mortality was 2.02% for off pump compared with 2.16 for on pump (p 0.390). Off-pump patients had lower rates of perioperative stroke (1.6% vs. 2.0%, p 0.003) and bleeding requiring an operation (1.6% vs. 2.2%, p 0.001) and higher rates of gastrointestinal bleeding, perforation, or infarction (1.2% vs. 0.9%, p 0.003). Off-pump patients had lower postoperative lengths of stay (median 5 days vs. 6 days, p 0.001). On-pump patients had higher three-year survival (adjusted risk ratio 1.086, p 0.045) and higher freedom from death or revascularization (adjusted risk ratio 1.232, p 0.001). These data raise major concerns about the efficacy of off-pump surgery. Part of this detriment in intermediateterm survival and need for subsequent revascularization may be attributed to the learning curve during the initial use of off-pump CABG by many New York surgeons. Patients undergoing off-pump operations in the last two years of the four-year study interval did not show a difference in

8 1524 Jones JACC Vol. 45, No. 9, 2005 Year in Cardiovascular Surgery May 3, 2005: intermediate-term survival compared with on-pump CABG patients. However, this 1999 to 2000 off-pump cohort still required more subsequent revascularization procedures. These New York data do not capture the initial intentionto-treat and reflect only the operative technique reported. Therefore, all detrimental outcomes from emergency conversions would have been assigned to the on-pump group, and the true detriment of off-pump surgery may have been greater than that reported. Failure to address the impact of emergency crossover from off- to on-pump CABG has flawed all previous randomized and observational studies of short- and intermediate-term mortality. An outstanding paper addressing this issue found that emergency crossover had a major negative influence on later mortality and morbidity (19). Because most patients who become unstable during attempts at off-pump CABG survive to undergo on-pump CABG, the magnitude of any survival detriment is doubled in a comparison made by operation received and not by intention-to-treat. The impact of this observation on interpretation of these previous studies is the subject of a Viewpoint article (20) in this issue of the Journal. Until a prospective randomized trial, such as the ongoing Veterans Affairs Outcomes Following Myocardial Revascularization: On and Off Cardiopulmonary Bypass (ROOBY) trial, addressing this issue is completed, the value of off-pump surgery will not be definitively known. Randomized trials related to the conduct of CABG surgery. Pexelizumab, a C5 complement inhibitor, was compared with placebo in a randomized double blind placebo-controlled trial of 3,099 patients undergoing CABG surgery with or without valve surgery for the primary composite end point of reduction of death or myocardial infarction at 30 days (21). Pexelizumab did not significantly reduce the primary end point in CABG-only patients but was associated with statistically significant reduction three days after the procedure among all patients undergoing CABG with or without valve surgery. The modest reduction in perioperative myocardial infarction (33 fewer in 3,099 patients), which was the dominant benefit of this agent, was offset by an almost two-fold increase in pneumonia (19 more in 2,990 patients). This agent would appear to have low value for cardiac surgical patients. The importance of tight diabetic control was assessed in 141 diabetic patients undergoing CABG who were prospectively randomized to glycemic control (serum glucose 1.5 to 200 mg/dl) with glucose-insulin-potassium or standard therapy using intermittent subcutaneous insulin (22). Patients treated with glucose-insulin-potassium had lower serum glucose levels, less atrial fibrillation (AF) perioperatively, shorter postoperative length of stay, and a survival advantage over the initial two years after surgery (Fig. 8). Patients with tight diabetic control also had fewer episodes of recurrent ischemia (5% vs. 19%, p 0.01) and fewer sternal or leg wound infections (1% vs. 10%, p 0.03). The results of this study in context of similar benefit found in Figure 8. Long-term survival. Survival was prolonged in patients treated with glucose-insulin-potassium because of a decreased rate of mortality in patients treated with glucose-insulin-potassium (GIK) over the initial two-year course after surgery. Reprinted with permission from Lazar et al. (22). previous observational studies suggest tight diabetic control should become the standard postoperative management for diabetic patients. ATRIAL FIBRILLATION Medical prophylaxis of AF in cardiac surgical patients. The value of the administration of prophylactic magnesium to reduce the incidence of supraventricular arrhythmias after cardiac surgery was evaluated by a meta-analysis of 17 trials that included data on 2,069 patients (23). This drug reduced the incidence of AF by 29% and ventricular arrhythmias by 48% but had no benefit on the length of hospitalization, incidence of myocardial infarction, or mortality. Another randomized trial of 202 patients reported in 2004 also supports the conclusion that prophylactic magnesium administration does not provide sufficient benefit to warrant its routine use in cardiac surgical patients (24). The efficacy of sotalol was compared with that of atenolol for prevention of AF in 253 consecutive patients randomized in an open-label randomized study (25). Atrial fibrillation occurred in 34 (22.2%) of the 153 atenolol-treated patients and in 10 (10%) of the 100 sotalol-treated patients (p 0.013). Sotalol prolonged QT intervals, but no severe proarrhythmic events were observed. Whether the modest observed decrease in AF warrants the added risk of proarrhythmic events with routine use of this agent in cardiac surgical patients remains unclear. Surgical prophylaxis of AF in cardiac surgical patients. Two observational studies have explored the value of cardiac denervation at the time of cardiac surgical operation for reducing postoperative AF. The role of ventral cardiac denervation for prevention of AF was examined in 207 patients by removing the nerves around the large vessels at the base of the heart beginning with the right side of the superior vena cava and continuing through the midportion of the anterior pulmonary artery (26). This dissection that removed fat pads surrounding the superior vena cava, aorta,

9 JACC Vol. 45, No. 9, 2005 May 3, 2005: Jones Year in Cardiovascular Surgery 1525 and anterior and right pulmonary arteries required an extra 5 min of operative time with no associated operative complications. The 219 subjects considered as nonrandomized controls were similar in baseline and operative characteristics except for fewer grafts per patient in the control group. Postoperative AF occurred in 15 (7%) of 207 patients undergoing ventral cardiac denervation and in 56 (27%) of 219 control subjects (p 0.001). After baseline differences were corrected by multivariable adjustment, ventral cardiac denervation remained the most significant negative predictor of postoperative AF. The 7% reported incidence of AF is remarkably low and, if confirmed in broader experience, would certainly justify adding this minimal modification to cardiac operations. The influence of parasympathetic nerves in the anterior fat pad was examined in 55 patients undergoing CABG who were randomly assigned to receive either dissection or no dissection of the anterior fat pad located between the base of the aorta and main pulmonary artery (27). Evoking sinus cycle length prolongation with stimulation identified the fat pad before cardiopulmonary bypass. Stimulation at the conclusion of surgery documented increased sinus cycle length in patients with the fat pad preserved and failure to increase sinus length documented denervation in patients with the fat pad removed. Removal of the fat pad increased postoperative AF from 37% compared with 7% in patients with the fat pad preserved. The authors suggest that dissection of the anterior fat pad, which often occurs incidental to cardiac surgery, may contribute to postoperative AF. Both of these studies of the influence of operative dissection of cardiac sympathetic and parasympathetic nerves identify a fruitful area for additional work directed toward the important goal of decreasing postoperative AF in cardiac surgical patients. Surgical treatment of chronic AF. The influence of preoperative atrial arrhythmias on long-term survival was examined in 451 (0.95%) of 46,984 patients who underwent isolated CABG (28). Before CABG, 411 of these patients had AF and 40 patients had atrial flutter. Multivariable logistic regression defined a propensity score that by pairwise propensity matching created groups with similar baseline characteristics with and without AF. Chronic AF decreased the average survival by an average of 1.7 years at 10 years follow-up and 2.9 years after 15 years follow-up. These data define the maximal potential survival that might be added to a population by a procedure that would eliminate AF at the time a patient with chronic AF undergoes coronary bypass grafting (26). A modified Cox maze III procedure conducted with bipolar radiofrequency energy in 40 consecutive patients undergoing cardiac surgical procedures was accomplished with no operative deaths and a mean additional operating time of 47 min (29). Follow-up magnetic resonance imaging showed no evidence of pulmonary vein stenosis, and atrial contraction was preserved in all patients. At the six-month follow-up, 91% of patients (21 of 23) were in sinus rhythm, and there were no late strokes. This procedure appears reasonable to add to patients with pre-existing chronic AF at the time of performing coronary bypass operations. SURGERY FOR HEART FAILURE Ventricular reconstruction. Observations on 285 consecutive patients who underwent ventricular reconstruction between 1983 and 2002 represent the largest report of long-term outcomes for this operation (30). The left ventricular reconstruction procedure was performed most commonly in the open beating heart using a modified linear closure and a septoplasty when indicated. The ejection fraction in the group averaged 24%, and 83% of patients had heart failure class III or IV preoperatively. Associated operative procedures included CABG in 92%, septoplasty in 22%, ablation for ventricular tachycardia in 41%, and mitral valve procedure in 2%. There were 69 deaths during follow-up that extended up to 19 years (mean, 63 months). The entire population showed an overall survival of 92% at 1 year, 82% at 5 years, and 62% at 10 years. The 82% 5-year survival in this group was higher than the 69% survival reported for the 22 of the 1,198 patients followed by the Reconstructive Endoventricular Surgery returning Torsion Original Radius Elliptical shape to the left ventricle (RESTORE) group through five years (31). Transmyocardial laser revascularization (TMR). Extended follow-up was obtained in 218 (83%) of 263 patients previously enrolled in a transmyocardial laser revascularization study between 1996 and 1998 (32). Patients had been characterized as those who would have been incompletely revascularized by CABG alone and, therefore, were subsequently randomly assigned to receive CABG alone or CABG/TMR with holmium:yag laser. At mean five-year follow-up, both groups had significant improvement of angina compared with baseline. The CABG/TMR group had a significantly lower proportion of patients with class III or greater angina (p 0.009). However, the number of angina-free patients was 78% for the TMR group versus 63% for the CABG group (p 0.08). Survival at six years was similar. From 1996 to 1998, a cohort of patients with medically refractory CCS class IV angina who were not candidates for additional methods of revascularization was randomized to receive TMR using the holmium:yag laser or continued maximum medical management (33). Long-term follow-up was conducted on 212 (77%) of 275 patients in the original study cohort. Medical management was pursued in 112 patients initially, and 29 of these patients met a priori criteria for treatment failure and crossed over to receive TMR. Therefore, long-term outcomes were assessed on a two-group intention-to-treat basis as defined by the original randomization and a three-group analysis that compared patients randomly assigned to receive TMR with patients

10 1526 Jones JACC Vol. 45, No. 9, 2005 Year in Cardiovascular Surgery May 3, 2005: randomly assigned to receive MED but excluding crossovers that were analyzed as the third group. At an average follow-up of five years, 16 (33%) of 48 patients treated with TMR were angina free compared with 4 (11%; p 0.02) of 36 patients managed medically. At five years, the intentionto-treat survival was increased for patients assigned to receive TMR compared with those assigned to medical management (65% vs. 52%; p 0.05). However, in the three-treatment analysis, survival estimates were 65%, 53%, and 48%, respectively, for randomly assigned TMR patients, medically managed patients excluding crossovers, and crossover patients (p 0.16). Whether TMR added survival benefit when patients initially were entered into the study as the intention-to-treat analysis suggests or whether the added mortality in medically treated patients by initial intention-to-treat analysis resulted from the mortality of TMR at the time of unnecessary crossover cannot be assessed from these data. Heart transplantation. Between April 1997 and March 1998, 60 patients undergoing heart transplantation were randomly assigned to a subgroup with (n 30) or without (n 30) a De Vega tricuspid valve annuloplasty performed on the donor heart before implantation (34). The group receiving hearts with a tricuspid valve annuloplasty had shorter intraoperative reperfusion times and higher mean pulmonary artery to central venous pressure differences. Early mortality from donor heart dysfunction was 4 in 30 patients who received hearts without the annuloplasty and 0 in 30 when patients received a donor heart in which the annuloplasty was performed. The percentage of patients with 2 or greater tricuspid valvular regurgitation was 34% in hearts without tricuspid annuloplasty but none in hearts with (p 0.05). These observations argue for including tricuspid annuloplasty as a routine adjunct with bicaval orthotopic heart transplantation. CARDIAC VALVE SURGERY Mitral valve. The need to add valve repair to coronary bypass grafting in patients with ischemic mitral regurgitation was investigated in 51 consecutive patients who underwent CABG and mitral valve repair from 1996 to 2001 (35). A propensity analysis used 24 covariates to match equal cohorts of similar patients with ischemic mitral regurgitation undergoing CABG during the same period that did not have mitral valve repair. Mitral regurgitation severity was 3 to 4 in 94% of the CABG group with mitral repair and 96% in the CABG-alone patients. Mortality occurred in two patients in each of the 51-patient groups. Survival was similar at all times during the five-year follow-up period with a mean group follow-up of 38 months. Whereas a mitral valve repair can be safely added to CABG in patients with ischemic mitral regurgitation, these data suggest that the impact of this operative strategy on survival may be minimal. An edge-to-edge (Alfieri) mitral valve repair holds the advantage of technical simplicity that may be useful in specific clinical circumstances (36). In 224 patients who underwent an Alfieri repair from January 1997 through October 2001, the dominant indication was ischemic cardiomyopathy in 143 patients. Concomitant ring annuloplasty was performed in 188 patients. Preoperative mitral regurgitation was 3 to 4 in 109 patients. At hospital discharge, 79% of patients had no mitral regurgitation, and only 5% of patients had 3 to 4 mitral regurgitation. During the first three postoperative months, absence of mitral regurgitation declined to 40%. Mitral valve functional stenosis was not a major issue, but the rapid reappearance of mitral regurgitation in a large number of patients suggests this technique should be reserved for specific clinical circumstances that make other repairs difficult. Aortic valve. A retrospective review was performed of 160 consecutive patients who underwent aortic valve repair between 1986 and 2001 for aortic insufficiency that was caused by annular dilation leading to central leakage or a bicuspid valve in more than two thirds of patients (37). Only one early death occurred, and two patients required repeat repair of the aortic valve during the initial hospitalization. During mean follow-up of 4.2 years, there were 16 late deaths. The risk of reoperation on the valve gradually increased to 15% by seven years of follow-up. This experience suggests aortic valve repair can be performed with low risk and reasonable freedom from valve failure. Because this procedure does not require chronic anticoagulation, it may represent a useful option for some patients who are willing to accept the low-but-definite risk of early failure to avoid the risks of anticoagulation. Tricuspid valve. The cohort of 790 patients who underwent tricuspid valve annuloplasty for tricuspid regurgitation from 1990 to 1997 reduced their incidence of 3 or 4 severity from 87% to 14% at time of hospital discharge (38). However, 3 or 4 tricuspid insufficiency gradually recurred over time on follow-up echocardiograms. Incorporation of a semirigid ring into the tricuspid annuloplasty accomplished the best long-term freedom from 3 or 4 mitral regurgitation that was more than 90% at five years. By contrast, techniques that did not incorporate annular support had recurrence rates of 3 or 4 tricuspid regurgitation approaching 50% by this time. Transtricuspid placement of pacemaker leads is a preventable cause of tricuspid regurgitation that should be avoided when possible. STATUS REPORT OF MAJOR ONGOING RANDOMIZED CLINICAL TRIALS IN CARDIAC SURGICAL PATIENTS Outcomes Following Myocardial Revascularization: On and Off Cardiopulmonary Bypass (ROOBY trial). SPON- SOR. Veterans Affairs Cooperative Study. PRINCIPAL INVESTIGATOR. Frederick L. Grover, MD (frederick.grover@uchsc.edu).

11 JACC Vol. 45, No. 9, 2005 May 3, 2005: Jones Year in Cardiovascular Surgery 1527 HYPOTHESIS. In properly selected patients, 30-day and one-year mortality and morbidity are equivalent when CABG is conducted with or without using cardiopulmonary bypass. SECONDARY END POINTS. Angiographic graft status, completeness of revascularization, recurrent ischemia, neuropsychologic status, quality of life, resource use. DESIGN. Randomization stratified by surgeon; urgent or elective isolated CABG procedures; 2,200 patients randomized within four years; one-year follow-up. JANUARY 2005 STATUS. More than 8,800 patients screened, 1,327 randomized; major exclusions: small, diffusely diseased coronary arteries (36%); conversion rates: 11.3% for off-to-on-pump and 3.0% for on-to-off-pump; outcomes of total group unadjusted death rate, all cause, both treatment arms: 30-day 1.3%, 6-month 20%, 1-year 2.7%, perioperative myocardial infarction 0.3%, return to operating room for bleeding (48 h) 1.8%, cardiac arrest 1.6%, repeat cardiac surgery 0.2%, stroke 1.1%, sternal wound infection 1.4%, and renal failure 1.3%. CLINICAL SITES. A total of 17 U.S. Veterans Affairs hospitals. Surgical Treatment for Ischemic Heart Failure (STICH trial). SPONSOR. National Institutes of Health. PRINCIPAL INVESTIGATOR. Robert H. Jones, MD (jones060@mc.duke.edu). HYPOTHESES. 1) CABG combined with intensive MED improves long-term survival compared with MED alone in 1,500 patients with left ventricular ejection fraction (LVEF) 0.35 and CAD amenable to CABG; 2) Adding surgical ventricular restoration (SVR) to CABG and MED improves survival free of cardiac hospitalization in 1,000 patients with LVEF 0.35, CAD amenable to CABG, and dominant anterior akinesia or dyskinesia. SECONDARY END POINTS. Cardiac mortality and morbidity, resource use, quality of life, noninvasive cardiac study predictor of primary end points by myocardial ischemia and viability, left ventricular size and function, neurohormonal and cytokine levels, and genetic polymorphisms or mutations. DESIGN. A total of 2,425 patients with a LVEF 0.35 and CAD amenable to CABG will be stratified on the basis of MED eligibility (no left main stenosis 50% or CCS angina class III) and SVR eligibility (dominant anterior akinesia or dyskinesia amenable to SVR). Patients eligible for either MED or CABG but not eligible for the SVR procedure (Stratum A) will be assigned randomly in equal proportions to MED versus CABG. Patients eligible for all three therapies (Stratum B) will be assigned randomly in equal proportions to MED, CABG, and CABG plus SVR. Patients whose angina or CAD severity makes them ineligible for MED but who are appropriate candidates for both CABG and SVR (Stratum C) will be assigned randomly in equal proportions to CABG versus CABG SVR. Use of patients in Stratum B assigned to CABG to address both primary hypotheses provides 2,500 end points from 2,425 enrolled patients. JANUARY 2005 STATUS. Hypothesis 1 enrollment: 363 patients; completion expected December Hypothesis 2 enrollment: 609 patients; completion expected December CLINICAL SITES. A total of 76 North American, European, Asian-Pacific, and South American enrolling sites. Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial. SPONSOR. National Institutes of Health. PRINCIPAL INVESTIGATOR. Valentin Fuster, MD (valetin.fuster@mssm.edu). HYPOTHESIS. In 2,400 diabetic patients with multivessel disease amenable to CABG and PCI and indication for revascularization, either CABG or PCI will be superior in preventing death, nonfatal myocardial infarction, and stroke. PRIMARY END POINT. One of the clusters of death, nonfatal myocardial infarction, and nonfatal stroke. SECONDARY END POINTS. Cardiovascular mortality, quality of life, cost. DESIGN. Multicenter, open label, two-arm with equal allocation, two-year enrollment, three years minimum followup, PCI with FDA-approved drug-eluting stent of choice. JANUARY 2005 STATUS. Recruiting 100 international sites. Reprint requests and correspondence: Dr. Robert H. Jones, Duke Clinical Research Institute, P.O. Box 17969, Durham, North Carolina jones060@mc.duke.edu. REFERENCES 1. Welke KF, Ferguson TB Jr., Coombs LP, et al. Validity of the Society of Thoracic Surgeons National Adult Cardiac Surgery Database. Ann Thorac Surg 2004;77: Herbert MA, Prince SL, Williams JL, Magee MJ, Mack MJ. Are unaudited records from an outcomes registry database accurate? Ann Thorac Surg 2004;77: ; discussion Sadanandan S, Cannon CP, Gibson CM, Murphy SA, DiBattiste PM, Braunwald E, for the TIMI Study Group. A risk score to estimate the likelihood of coronary artery bypass surgery during the index hospitalization among patients with unstable angina and non ST-segment elevation myocardial infarction. J Am Coll Cardiol 2004;44: Rothenberg BM, Pearson T, Zwanziger J, Mukamel D. Explaining disparities in access to high-quality cardiac surgeons. Ann Thorac Surg 2004;78: Wu C, Hannan EL, Ryan TJ, et al. Is the impact of hospital and surgeon volumes on the in-hospital mortality rate for coronary artery bypass graft surgery limited to patients at high risk? Circulation 2004;110:784 9.