Multicenter experience with valve-in-valve transcatheter aortic valve replacement compared with primary, native valve transcatheter aortic valve replacement.

BACKGROUND: Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) offers an alternative to reoperative surgical aortic valve replacement. The short- and intermediate-term outcomes after ViV TAVR in the real world are not entirely clear. PATIENTS AND METHODS: A multicenter, retrospective analysis of a consecutive series of 121 ViV TAVR patients and 2200 patients undergoing primary native valve TAVR from 2012 to 2017 at six medical centers. The main outcome measures were in-hospital mortality, 30-day mortality, stroke, myocardial infarction, acute kidney injury, and pacemaker implantation. RESULTS: ViV patients were more likely male, younger, prior coronary artery bypass graft, "hostile chest," and urgent. 30% of the patients had Society of Thoracic Surgeons risk score <4%, 36.3% were 4%-8% and 33.8% were >8%. In both groups many patients had concomitant coronary artery disease. Median time to prosthetic failure was 9.6 years (interquartile range: 5.5-13.5 years). 82% of failed surgical valves were size 21, 23, or 25 mm. Access was 91% femoral. After ViV, 87% had none or trivial aortic regurgitation. Mean gradients were <20 mmHg in 54.6%, 20-29 mmHg in 30.6%, 30-39 mmHg in 8.3% and ≥40 mmHg in 5.87%. Median length of stay was 4 days. In-hospital mortality was 0%. 30-day mortality was 0% in ViV and 3.7% in native TAVR. There was no difference in in-hospital mortality, postprocedure myocardial infarction, stroke, or acute kidney injury. CONCLUSION: Compared to native TAVR, ViV TAVR has similar peri-procedural morbidity with relatively high postprocedure mean gradients. A multidisciplinary approach will help ensure patients receive the ideal therapy in the setting of structural bioprosthetic valve degeneration.

Comparative effectiveness of revascularization strategies for early coronary artery disease: A multicenter analysis.

OBJECTIVES: The goal of this analysis was to examine the comparative effectiveness of coronary artery bypass grafting versus percutaneous coronary intervention among patients aged less than 60 years. METHODS: We performed a multicenter, retrospective analysis of all cardiac revascularization procedures from 2005 to 2015 among 7 medical centers. Inclusion criteria were age less than 60 years and 70% stenosis or greater in 1 or more major coronary artery distribution. Exclusion criteria were left main 50% or greater, ST-elevation myocardial infarction, emergency status, and prior revascularization procedure. After applying inclusion and exclusion criteria, the final study cohort included 1945 patients who underwent cardiac surgery and 2938 patients who underwent percutaneous coronary intervention. The primary end point was all-cause mortality stratified by revascularization strategy. Secondary end points included stroke, repeat revascularization, and 30-day mortality. We used inverse probability weighting to balance differences among the groups. RESULTS: After adjustment, there was no significant difference in 30-day mortality (surgery: 0.8%; percutaneous coronary intervention: 0.7%, P = .86) for patients with multivessel disease. Patients undergoing surgery had a higher risk of stroke (1.3% [n = 25] vs 0.07% [n = 2], P < .001). Overall, surgery was associated with superior 10-year survival compared with percutaneous coronary intervention (hazard ratio, 0.71; 95% confidence interval, 0.57-0.88; P = .002). Repeat procedures occurred in 13.4% (n = 270) of the surgery group and 36.4% (n = 1068) of the percutaneous coronary intervention group, with both groups mostly undergoing percutaneous coronary intervention as their second operation. Accounting for death as a competing risk, at 10 years, surgery resulted in a lower cumulative incidence of repeat revascularization compared with percutaneous coronary intervention (subdistribution hazard ratio, 0.34; 95% confidence interval, 0.28-0.40; P < .001). CONCLUSIONS: Among patients aged less than 60 years with 2-vessel disease that includes the left anterior descending or 3-vessel coronary artery disease, surgery was associated with greater long-term survival and decreased risk of repeat revascularization.

Cardiac Surgery Outcomes: A Case for Increased Screening and Treatment of Obstructive Sleep Apnea.

BACKGROUND: Because of the limited published information on complications that obstructive sleep apnea (OSA) patients experience during and after cardiac surgery, we investigated OSA as a risk factor for postoperative outcomes. METHODS: This project used the Northern New England Cardiovascular Disease Study Group's data collected between 2011 and 2017 based on The Society of Thoracic Surgeons Adult Cardiac Surgery Database Data Collections form. A retrospective analysis of 1555 patients with OSA and 10,450 patients without OSA across 5 medical centers undergoing isolated coronary artery bypass grafting, isolated valve surgery, and combined coronary artery bypass grafting valve surgery was conducted. We used 1:1 nearest-neighbor propensity score matching with no replacement to balance characteristics among patients with and without OSA. RESULTS: There was a statistically significant increased risk of postoperative pneumonia, increased length of total and postoperative stay, and time to initial extubation. Two outcomes trended toward significance: intra- and postoperative intraaortic balloon pump use. Outcomes that failed to show statistical significance were surgical site infection, atrial fibrillation, cerebrovascular accident, permanent pacemaker placement, and blood products given. A chart review conducted on a subset of the study cohort revealed that more than 40% of OSA patients did not receive continuous positive airway pressure or bilevel positive airway pressure therapy postoperatively during their hospitalization. CONCLUSIONS: Our study aligns with the literature in concluding that OSA has deleterious effects on postoperative outcomes of cardiac surgery patients. Further research to better stratify OSA patients by severity are still needed. Additionally heightened awareness of the need to screen, diagnose, and properly treat patients for OSA is needed.

Assessment of the Early Disabling Effects of Coronary Artery Bypass Graft Surgery Using Direct Measures of Physical Function.

PURPOSE: Coronary artery bypass graft (CABG) surgery is an important treatment option in patients with coronary artery disease. Despite its beneficial effects, CABG surgery and its subsequent hospitalization may reduce physical functional capacity in patients, contributing to physical disability. Our objective was to assess the early disabling effects of CABG surgery and its subsequent hospitalization using direct measurements of physical function. METHODS: Patients (n = 44) were assessed pre-surgery and at hospital discharge for physical function using the Short Physical Performance Battery (SPPB) and self-reported physical and mental health by questionnaire. RESULTS: The total SPPB score (P < .001) and all of its components (P < .01-.001) decreased markedly following CABG surgery and hospitalization, with greater reductions in total SPPB score (P < .05) and gait speed (P < .01) in patients with higher body mass index. While CABG surgery and hospitalization reduced patient-reported physical function, changes in these indices largely did not correlate with changes in SPPB outcomes. CONCLUSION: Our results show the early disabling effects of CABG surgery and hospitalization on directly measured physical function, and that patients with higher body mass index had greater reductions. In addition, our results underscore the need to perform direct measurements of physical function to describe reductions in physiological functional capacity. These findings suggest the need for inpatient rehabilitation or early mobility programs to address this decline in physical function.

Improvement in Physical Function After Coronary Artery Bypass Graft Surgery Using a Novel Rehabilitation Intervention: A RANDOMIZED CONTROLLED TRIAL.

PURPOSE: Cardiorespiratory and skeletal muscle deconditioning occurs following coronary artery bypass graft surgery and hospitalization. Outpatient, phase 2 cardiac rehabilitation (CR) is designed to remediate this deconditioning but typically does not begin until several weeks following hospital discharge. Although an exercise program between discharge and the start of CR could improve functional recovery, implementation of exercise at this time is complicated by postoperative physical limitations and restrictions. Our objective was to assess the utility of neuromuscular electrical stimulation (NMES) as an adjunct to current rehabilitative care following postsurgical discharge and prior to entry into CR on indices of physical function in patients undergoing coronary artery bypass graft surgery. METHODS: Patients were randomized to 4 wk of bilateral, NMES (5 d/wk) to their quadriceps muscles or no intervention (control). Physical function testing was performed at hospital discharge and 4 wk post-discharge using the Short Physical Performance Battery and the 6-min walk tests. Data from 37 patients (19 control/18 NMES) who completed the trial were analyzed. The trial was registered at ClinicalTrials.gov (NCT03892460). RESULTS: Physical function measures improved from discharge to 4 wk post-surgery across our entire cohort (P < .001). Patients randomized to NMES, however, showed greater improvements in 6-min walk test distance and power output compared with controls (P < .01). CONCLUSION: Our results provide evidence supporting the utility of NMES to accelerate recovery of physical function after coronary artery bypass graft surgery.

The 30-Year Influence of a Regional Consortium on Quality Improvement in Cardiac Surgery.

BACKGROUND: The Northern New England Cardiovascular Disease Study Group (NNECDSG) was founded in 1987 as a regional consortium to improve cardiovascular quality in Maine, New Hampshire, and Vermont. We sought to assess the longitudinal impact of the NNECDSG on quality and cost of coronary artery bypass grafting (CABG) during the past 30 years. METHODS: Patients undergoing isolated CABG at 5 medical centers from 1987-2017 were retrospectively reviewed (n = 67,942). They were divided into 4 time periods: 1987-1999 (n = 36,885), 2000-2005 (n = 14,606), 2006-2011(n = 8470), and 2012-2017 (n = 7981). The first period was the time the NNECDSG initiated a series of quality improvement initiatives including data feedback, quality improvement training, process mapping, and site visits. RESULTS: Throughout the 4 time intervals, there was a consistent decline in in-hospital mortality, from 3.4% to 1.8% despite an increase in predicted risk of mortality (P < .001), and a significant decline in in-hospital morbidity, including return to the operating room for bleeding, acute kidney injury, mediastinitis, and low output failure (P < .001). Median length of stay decreased from 7 to 5 days (P < .001), which translated into potential savings of $82,722,023. There was a decrease in use of red blood cells from 3.1 units to 2.6 units per patient in the most current time, which translated into potential savings of $1,985,456. CONCLUSIONS: By using collaborative quality improvement initiatives, the NNECDSG has succeeded in significant, sustained improvements in quality and cost for CABG during the past 30 years. These data support the utility of a regional consortium in improving quality.

A complicated abscess from a dropped gallstone.

Laparoscopic cholecystectomies represent one of the most common procedures of General Surgery. Dropped gallstones during laparoscopic cholecystectomy is a rare occurrence but can potentially lead to morbid complications. We present a rare case of a broncho-pleuro-cutaneous fistula in a patient with recurrent abscess formations after an elective laparoscopic cholecystectomy. The fistula formed over 3 years from a gallstone that eroded through the diaphragm, into the pleural space, and eventually into a terminal bronchiole. Bilirubin staining within the fistula tract was confirmed on hematoxylin and eosin staining.

Tissue versus mechanical aortic valve replacement in younger patients: A multicenter analysis.

OBJECTIVE: The goal of this study was to examine the long-term survival of patients between the ages of 50 and 65 years who underwent tissue versus mechanical aortic valve replacement (AVR) in a multicenter cohort. METHODS: A multicenter, retrospective analysis of all AVR patients (n = 9388) from 1991 to 2015 among 7 medical centers reporting to a prospectively maintained clinical registry was conducted. Inclusion criteria were: patients aged 50 to 65 years who underwent isolated AVR. Baseline comorbidities were balanced using inverse probability weighting for a study cohort of 1449 AVRs: 840 tissue and 609 mechanical. The primary end point of the analysis was all-cause mortality. Secondary end points included in-hospital morbidity, 30-day mortality, length of stay, and risk of reoperation. RESULTS: During the study period, there was a significant shift from mechanical to tissue valves (P < .001). There was no significant difference in major in-hospital morbidity, mortality, or length of hospitalization. Also, there was no significant difference in adjusted 15-year survival between mechanical versus tissue valves (hazard ratio, 0.87; 95% confidence interval [CI], 0.67-1.13; P = .29), although tissue valves were associated with a higher risk of reoperation with a cumulative incidence of 19.1% (95% CI, 14.4%-24.3%) versus 3.0% (95% CI, 1.7%-4.9%) for mechanical valves. The reoperative 30-day mortality rate was 2.4% (n = 2) for the series. CONCLUSIONS: Among patients 50 to 65 years old who underwent AVR, there was no difference in adjusted long-term survival according to prosthesis type, but tissue valves were associated with a higher risk of reoperation.

Surgical Atrial Fibrillation Ablation Improves Long-Term Survival: A Multicenter Analysis.

BACKGROUND: The Society of Thoracic Surgeons guidelines recommend surgical ablation (SA) at the time of concomitant mitral operations, aortic valve replacement, coronary artery bypass grafting (CABG), and aortic valve replacement plus CABG for patients in atrial fibrillation (AF). The goal of this analysis was to assess the influence of SA on long-term survival. METHODS: A retrospective analysis of 20,407 consecutive CABG or valve procedures from 2008 to 2015 among seven centers reporting to a prospectively maintained clinical registry was conducted. Patients undergoing operation with documented preoperative AF were included (n = 2,740). Patients receiving SA were compared with patients receiving no SA. The primary end point was all-cause mortality. Secondary end points included in-hospital morbidity and mortality. RESULTS: The frequency of SA was 23.1% (n = 634), and an increase was seen in the rate of SA over the study period (p < 0.001). Concomitant SA was performed in 16.2% of CABG, 30.6% of valve, and 24.3% of valve plus CABG procedures. A substantial improvement was found in unadjusted survival among patients undergoing SA (hazard ratio 0.54, 95% confidence interval: 0.42 to 0.70). Moreover, no differences were found in postoperative complications. SA did have longer bypass times (p < 0.001) but a shorter overall length of stay (p < 0.001). After risk adjustment, SA patients had an improved 5-year survival (hazard ratio 0.69, 95% confidence interval: 0.51 to 0.92), and the effect was observed across all operations. CONCLUSIONS: In a multicenter cohort of patients with AF, concomitant SA resulted in substantially improved long-term survival across patients who underwent CABG, valve, and valve plus CABG. These findings support current guidelines from The Society of Thoracic Surgeons that recommend broader application of concomitant SA.

Intensity of Glycemic Control Affects Long-Term Survival After Coronary Artery Bypass Graft Surgery.

BACKGROUND: A patient's hemoglobin (Hb) A1c level, regardless of diabetic status, is a measure of glycemic control. Studies have found it is an independent predictor of short-term death in patients undergoing coronary artery bypass grafting (CABG). In this study, we used preoperative HbA1c to assess whether levels are associated with short-term and long-term survival after CABG. METHODS: From a regional registry of consecutive cases, we identified 6,415 patients undergoing on-pump isolated CABG from 2008 to 2015 with documented preoperative HbA1c level. We defined four HbA1c groups: less than 5.7% (n = 1,713), 5.7% to 6.4% (n = 2,505), 6.5% to 8.0% (n = 1,377), and more than 8% (n = 820). Relationship to in-hospital outcomes and long-term survival was assessed. Outcome rates and hazard ratios were adjusted for patient and disease risk factors using multivariable logistic regression and Cox models. RESULTS: The study included 3,740 patients (58%) not diagnosed as having diabetes and 2,674 with diabetes. Prediabetes (HbA1c 5.7% to 6.4%) was documented in 52% (n = 1,933) of nondiabetic patients. Higher HbA1c values were associated with younger age, female sex, greater body mass index, more comorbid diseases, lower ejection fraction, more 3-vessel coronary disease, and recent myocardial infarction (p < 0.05 trend for all). After adjustment for patient risk, greater HbA1c values were not associated with higher rates of in-hospital death or morbidity. Long-term survival was significantly worse as HbA1c increased. Risk of death increased by 13% for every unit increase in HbA1c (adjusted hazard ratio, 1.13; 95% confidence interval, 1.07 to 1.19; p < 0.001). CONCLUSIONS: Preadmission glycemic control, as assessed by HbA1c, is predictive of long-term survival, with higher levels associated with poorer prognosis. Whether this risk can be modified by better glycemic control postoperatively remains to be determined.

Comparative effectiveness of coronary artery bypass grafting versus percutaneous coronary intervention in a real-world Surgical Treatment for Ischemic Heart Failure trial population.

OBJECTIVE: There are no prospective randomized trial data to guide decisions on optimal revascularization strategies for patients with multivessel coronary artery disease and reduced ejection fraction. In this analysis, we describe the comparative effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in this patient population. METHODS: A multicenter, retrospective analysis of all CABG (n = 18,292) and PCIs (n = 55,438) performed from 2004 to 2014 among 7 medical centers reporting to the Northern New England Cardiovascular Disease Study Group. After applying inclusion and exclusion criteria from the Surgical Treatment for Ischemic Heart Failure trial, there were 955 CABG and 718 PCI patients with an ejection fraction ≤ 35% and 2- or 3-vessel disease. Inverse probability weighting was used for risk adjustment. The primary end point was all-cause mortality. Secondary end points included rates of 30-day mortality, stroke, acute kidney injury, and incidence of repeat revascularization. RESULTS: The median duration of follow-up was 4.3 years (range, 1.59-6.71 years). CABG was associated with improved long-term survival compared with PCI after risk adjustment (hazard ratio, 0.59; 95% confidence interval, 0.50-0.71; P < .01). Although CABG and PCI had similar 30-day mortality rates (P = .14), CABG was associated with a higher frequency of stroke (P < .001) and acute kidney injury (P < .001), whereas PCI was associated with a higher incidence of repeat revascularization (P < .001). CONCLUSIONS: Among patients with reduced ejection fraction and multivessel disease, CABG was associated with improved long-term survival compared with PCI. CABG should be strongly considered in patients with ischemic cardiomyopathy and multivessel coronary disease.

Coronary Revascularization With Single Versus Bilateral Mammary Arteries: Is It Time to Change?

BACKGROUND: Arterial conduits are preferred to venous conduits for coronary artery bypass grafting because of longer patency. A single internal mammary artery (SIMA) is used routinely. Bilateral internal mammary arteries (BIMA) are used less frequently. We sought to determine whether BIMA were superior to SIMA. METHODS: From our regional registry of consecutive open heart operations, we identified 47,984 patients who underwent isolated coronary artery bypass grafting from 1992 to 2014. Of the 1,482 BIMA patients, 1,297 were propensity matched to a cohort of SIMA patients. Short-term outcomes were compared using standard statistical techniques. Long-term survival was compared using Kaplan-Meier estimators and compared using a log-rank test. RESULTS: BIMA patients were younger and had fewer comorbid conditions than SIMA patients. After propensity weighting, BIMA and SIMA patients were well matched. There was no difference in in-hospital outcomes for BIMA versus SIMA patients for mortality (1.2% [n = 15] vs 0.8% [n = 10], p = 0.315), stroke (0.7% [n = 9] vs 0.7% [n = 9), p = 1.000), bleeding (2.2% [n = 28] vs 2.8% [n = 36], p = 0.311), or mediastinitis (0.8% [n = 10] vs 0.9% [n = 12], p = 0.667). The median follow-up was 12 years. Survival was better for BIMA than SIMA (adjusted hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.91; p < 0.001). Survival curves began to separate after 5 years. At 15 years, the absolute difference in survival was 8.4%. CONCLUSIONS: In a large regional experience, BIMA is associated with no upfront risk of adverse events and improved long-term survival compared with SIMA. Our results indicate that BIMA conduits should be considered more frequently during coronary artery bypass grafting due to their demonstrated survival advantage.

Ten-year clinical experience of humanitarian cardiothoracic surgery in Rwanda: Building a platform for ultimate sustainability in a resource-limited setting.

OBJECTIVE: Despite its near complete eradication in resource-rich countries, rheumatic heart disease remains the most common acquired cardiovascular disease in sub-Saharan Africa. With a ratio of physicians/population of 1 per 10,500, including only 4 cardiologists for a population of 11.4 million, Rwanda represents a resource-limited setting lacking the local capacity to detect and treat early cases of strep throat and perform lifesaving operations for advanced rheumatic heart disease. Humanitarian surgical outreach in this region can improve the delivery of cardiovascular care by providing sustainability through mentorship, medical expertise, training, and knowledge transfer, and ultimately the creation of a cardiac center. METHODS: We describe the experience of consecutive annual visits to Rwanda since 2008 and report the outcomes of a collaborative approach to enable sustainable cardiac surgery in the region. The Ferrans and Powers Quality of Life Index tool's Cardiac Version (http://www.uic.edu/orgs/qli/) was administered to assess the postoperative quality of life. RESULTS: Ten visits have been completed, performing 149 open procedures, including 200 valve implantations, New York Heart Association class III or IV, with 4.7% 30-day mortality. All procedures were performed with the participation of local Rwandan personnel, expatriate physicians, nurses, residents, and support staff. Early complications included cerebrovascular accident (n = 4), hemorrhage requiring reoperation (n = 6), and death (n = 7). Quality of life was assessed to further understand challenges encountered after cardiac surgery in this resource-limited setting. Four major domains were considered: health and functioning, social and economic, psychologic/spiritual, and family. The mean total quality of life index was 20.79 ± 4.07 on a scale from 0 to 30, for which higher scores indicated higher quality of life. Women had significantly lower "social and economic" subscores (16.81 ± 4.17) than men (18.64 ± 4.10) (P < .05). Patients who reported receiving their follow-up care in rural health centers also had significantly lower "social and economic" subscores (15.67 ± 3.81) when compared with those receiving follow-up care in urban health facilities (18.28 ± 4.16) (P < .005). Value afforded to family and psychologic factors remained high among all groups. Major postsurgical challenges faced included barriers to follow-up and systemic anticoagulation. CONCLUSIONS: This report represents the first account of a long-term humanitarian effort to develop sustainability in cardiac surgery in a resource-limited setting, Rwanda. With the use of volunteer teams to deliver care, transfer knowledge, and mentor local personnel, the results demonstrate superior outcomes and favorable indices of quality of life. The credibility gained over a decade of effort has created the opportunity for a partnership with Rwanda to establish a dedicated center of cardiac care to assist in mitigating the burden of cardiovascular disease throughout sub-Saharan Africa.

Should Diabetes Be a Contraindication to Bilateral Internal Mammary Artery Grafting?

BACKGROUND: This study evaluates the influence of bilateral internal mammary artery (BIMA) versus single internal mammary artery (SIMA) grafting on postoperative morbidity and long-term survival among diabetic patients undergoing coronary artery bypass grafting (CABG). METHODS: A multicenter, retrospective analysis of 47,984 consecutive CABGs performed from 1992 to 2014 at 7 medical centers was conducted. Among the study population, 1,482 CABGs with BIMA were identified, and 1,297 BIMA patients were propensity-matched to 1,297 SIMA patients. The study cohort for this analysis, drawn from matched data, included 430 diabetic patients: 217 SIMA and 213 BIMA. The primary endpoint was long-term survival. Secondary endpoints included postoperative morbidity, length of stay, and in-hospital mortality. RESULTS: The median duration of follow-up was 9.3 (range, 4.3 to 13.9) years. Among propensity-matched diabetic patients, there was no significant difference in age, body mass index, or major baseline comorbidities. The groups were also well matched on the number of diseased coronary arteries and number of distal anastomoses performed. There was no difference in the rate of mediastinitis or sternal dehiscence (p = 0.503) or in-hospital mortality (p = 0.758) between groups. Both groups had a similar median length of stay of 5 (range, 4 to 7) days. Diabetic patients who received a BIMA had significantly improved long-term survival when compared with SIMA patients (hazard ratio 0.75 [95% confidence interval 0.57 to 0.98], p = 0.034). CONCLUSIONS: Among diabetics undergoing CABG, use of BIMA grafting does not result in increased in-hospital morbidity or mortality and confers a long-term survival advantage when compared with SIMA grafting. Thus, diabetic patients should be considered for BIMA grafting more frequently.

Does Use of Bilateral Internal Mammary Artery Grafting Reduce Long-Term Risk of Repeat Coronary Revascularization? A Multicenter Analysis.

BACKGROUND: Although previous studies have demonstrated that patients receiving bilateral internal mammary artery (BIMA) conduits during coronary artery bypass grafting have better long-term survival than those receiving a single internal mammary artery (SIMA), data on risk of repeat revascularization are more limited. In this analysis, we compare the timing, frequency, and type of repeat coronary revascularization among patients receiving BIMA and SIMA. METHODS: We conducted a multicenter, retrospective analysis of 47 984 consecutive coronary artery bypass grafting surgeries performed from 1992 to 2014 among 7 medical centers reporting to a prospectively maintained clinical registry. Among the study population, 1482 coronary artery bypass grafting surgeries with BIMA were identified, and 1297 patients receiving BIMA were propensity-matched to 1297 patients receiving SIMA. The primary end point was freedom from repeat coronary revascularization. RESULTS: The median duration of follow-up was 13.2 (IQR, 7.4-17.7) years. Patients were well matched by age, body mass index, major comorbidities, and cardiac function. There was a higher freedom from repeat revascularization among patients receiving BIMA than among patients receiving SIMA (hazard ratio [HR], 0.78 [95% CI, 0.65-0.94]; P=0.009). Among the matched cohort, 19.4% (n=252) of patients receiving SIMA underwent repeat revascularization, whereas this frequency was 15.1% (n=196) among patients receiving BIMA (P=0.004). The majority of repeat revascularization procedures were percutaneous coronary interventions (94.2%), and this did not differ between groups (P=0.274). Groups also did not differ in the ratio of native versus graft vessel percutaneous coronary intervention (P=0.899), or regarding percutaneous coronary intervention target vessels; the most common targets in both groups were the right coronary (P=0.133) and circumflex arteries (P=0.093). In comparison with SIMA, BIMA grafting was associated with a reduction in all-cause mortality at 12 years of follow-up (HR, 0.79 [95% CI, 0.69-0.91]; P=0.001), and there was no difference in in-hospital morbidity. CONCLUSIONS: BIMA grafting was associated with a reduced risk of repeat revascularization and an improvement in long-term survival and should be considered more frequently during coronary artery bypass grafting.

Optimal Timing From Myocardial Infarction to Coronary Artery Bypass Grafting on Hospital Mortality.

BACKGROUND: Whether delaying coronary artery bypass grafting (CABG) after myocardial infarction (MI) is associated with better outcomes or is an unnecessary use of health care resources is unclear. This study investigated the relationship between MI-to-CABG timing on in-hospital death. METHODS: From the Northern New England Cardiovascular Disease Study Group (NNE) Cardiac Surgery Registry we identified 3,060 isolated CABG patients with prior MI from 2008 to 2014. We compared in-hospital death by MI-to-CABG timing of less than 1 day, 1 to 2 days, 3 to 7 days, and 8 to 21 days. We adjusted for patient characteristics using logistic regression. RESULTS: Among patients with prior MI, CABG was performed within 1 day for 99 (3.2%), 1 to 2 days for 369 (12.1%), 3 to 7 days for 1,966 (64.3%), and 8 to 21 days for 626 (20.5%) patients. NNE-predicted mortality was similar for patients operated on within 1 day (1.8%), 1 to 2 days (1.8%), and 3 to 7 days (1.9%), but was higher for 8 to 21 days (2.4%) of MI. Crude in-hospital mortality was higher for those with MI-to-CABG time of less than 1 day (5.1%) compared with 1 to 2 days (1.6%), 3 to 7 days (1.6%), and 8 to 21 days (2.7%, p = 0.044). Adjusted in-hospital mortality remained high for less than 1 day (5.4%; 95% CI, 1.5% to 9.4%), and similar for 1 to 2 days (1.8%; 95% CI, 0.4% to 3.1%), 3 to 7 days (1.7%; 95% CI, 1.1% to 2.3%), and 8 to 21 days (2.3%; 95% CI, 1.2% to 3.3%) between MI and CABG. CONCLUSIONS: Patients operated on 1 to 2 days and 3 to 7 days after MI had a similar mortality rate, suggesting it may be possible to reduce the MI-to-CABG interval for some patients without sacrificing outcomes. Patients operated on within 1 day after MI had a higher mortality rate.

Disabling Mitochondrial Peroxide Metabolism via Combinatorial Targeting of Peroxiredoxin 3 as an Effective Therapeutic Approach for Malignant Mesothelioma.

Dysregulation of signaling pathways and energy metabolism in cancer cells enhances production of mitochondrial hydrogen peroxide that supports tumorigenesis through multiple mechanisms. To counteract the adverse effects of mitochondrial peroxide many solid tumor types up-regulate the mitochondrial thioredoxin reductase 2--thioredoxin 2 (TRX2)--peroxiredoxin 3 (PRX3) antioxidant network. Using malignant mesothelioma cells as a model, we show that thiostrepton (TS) irreversibly disables PRX3 via covalent crosslinking of peroxidatic and resolving cysteine residues in homodimers, and that targeting the oxidoreductase TRX2 with the triphenylmethane gentian violet (GV) potentiates adduction by increasing levels of disulfide-bonded PRX3 dimers. Due to the fact that activity of the PRX3 catalytic cycle dictates the rate of adduction by TS, immortalized and primary human mesothelial cells are significantly less sensitive to both compounds. Moreover, stable knockdown of PRX3 reduces mesothelioma cell proliferation and sensitivity to TS. Expression of catalase in shPRX3 mesothelioma cells restores defects in cell proliferation but not sensitivity to TS. In a SCID mouse xenograft model of human mesothelioma, administration of TS and GV together reduced tumor burden more effectively than either agent alone. Because increased production of mitochondrial hydrogen peroxide is a common phenotype of malignant cells, and TS and GV are well tolerated in mammals, we propose that targeting PRX3 is a feasible redox-dependent strategy for managing mesothelioma and other intractable human malignancies.