Increased risk of atrial fibrillation among patients undergoing coronary artery bypass graft surgery while receiving nitrates and antiplatelet agents.

Background Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass graft (CABG) surgery. This arrhythmia occurs more frequently among patients who receive perioperative inotropic therapy (PINOT). Administration of nitrates with antiplatelet agents reduces the conversion rate of cyclic guanosine monophosphate to guanosine monophosphate. This process is associated with increased concentrations of free radicals, catecholamines, and blood plasma volume. We hypothesized that patients undergoing CABG surgery who receive PINOT may be more susceptible to POAF when nitrates are administered with antiplatelet agents. Methods Clinical records were examined from a prospectively maintained cohort of 4,124 patients undergoing primary isolated CABG surgery to identify POAF-associated factors. Results POAF risk was increased among patients receiving PINOT, and the greatest effect was observed when nitrates were administered with antiplatelet therapy. Adjustment for comorbidities did not substantively change the study results. Conclusions Administration of nitrates with certain antiplatelet agents was associated with an increased POAF risk among patients undergoing CABG surgery. Additional studies are needed to determine whether preventive strategies such as administration of antioxidants will reduce this risk.

Factors Associated with Discharge to a Skilled Nursing Facility after Transcatheter Aortic Valve Replacement Surgery.

An assumption regarding transcatheter aortic valve replacement (TAVR), a minimally invasive procedure for treating aortic stenosis, is that patients remain at, or near baseline and soon return to their presurgical home to resume activities of daily living. However, this does not consistently occur. The purpose of this study was to identify preoperative factors that optimally predict discharge to a skilled nursing facility (SNF) after TAVR. Delineation of these conditions is an important step in developing a risk stratification model to assist in making informed decisions. Data was extracted from the American College of Cardiology (ACC) transcatheter valve therapy (TVT) registry and the Society of Thoracic Surgeons (STS) database on 285 patients discharged from 2012⁻2017 at a tertiary referral heart institute located in the southeastern region of the United States. An analysis of assessment, clinical and demographic variables was used to estimate relative risk (RR) of discharge to a SNF. The majority of participants were female (55%) and white (84%), with a median age of 82 years (interquartile range = 9). Approximately 27% (n = 77) were discharged to a SNF. Age > 75 years (RR = 2.3, p = 0.0026), female (RR = 1.6, p = 0.019), 5-meter walk test (5MWT) >7 s (RR = 2.0, p = 0.0002) and not using home oxygen (RR = 2.9, p = 0.0084) were identified as independent predictive factors for discharge to a SNF. We report a parsimonious risk-stratification model that estimates the probability of being discharged to a SNF following TAVR. Our findings will facilitate making informed treatment decisions regarding this older patient population.

Perioperative Inotrope Therapy and Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery: Evidence of a Racial Disparity.

BACKGROUND AND OBJECTIVE: Following coronary artery bypass graft (CABG) surgery, mortality rates are significantly higher among black patients who experience postoperative atrial fibrillation (POAF). Perioperative inotropic therapy (PINOT) was associated with POAF in previous reports, but the extent to which race influences this association is unknown. In the present study, the relationship between PINOT, race, and POAF was examined in patients undergoing CABG surgery. METHODS AND SETTING: Clinical records were examined from a prospectively maintained cohort of 11,855 patients (median age 64 yrs; 70% male; 16% black) undergoing primary isolated CABG at a large cardiovascular institute in the southeastern region of the United States. Relative risk (RR) and 95% confidence intervals (CIs) were computed using log-binomial regression. MAIN RESULTS: The association between PINOT and POAF was significantly increased among black patients (adjusted RR 1.7, CI 1.4-2.0) compared with white patients (adjusted RR 1.3, CI 1.2-1.4) (pinteraction  = 0.013). CONCLUSIONS: These findings suggest that PINOT may be disproportionately associated with POAF among black patients undergoing CABG surgery. Additional studies are needed to examine further the potential underlying mechanisms of this association.

Plasma Catecholamine Levels on the Morning of Surgery Predict Post-Operative Atrial Fibrillation.

OBJECTIVES: This study sought to determine whether plasma catecholamines and monoamine oxidase-B (MOA-B) are associated with post-operative atrial fibrillation (POAF) in patients undergoing elective cardiac surgery. BACKGROUND: Although intra- and post-operative adrenergic tone has been demonstrated to be an causative factor for POAF, the role and association of pre-operative plasma catecholamines remains unclear. METHODS: Prior to administration of anesthesia on the morning of surgery, blood samples were obtained from 324 patients undergoing nonemergent coronary artery bypass graft and/or aortic valve surgery with cardiopulmonary bypass at East Carolina Heart Institute. The concentrations of norepinephrine (NE), dopamine (DA), epinephrine (EPI), and enzyme MAO-B were assessed in platelet-rich plasma. A log-binomial regression model was used to determine the association between quartiles of these variables and POAF. RESULTS: Levels of NE (p = 0.0006) and EPI (p = 0.047) in the 4th quartile [Formula: see text] were positively associated with POAF, whereas DA (p = 0.0034) levels in the 4th quartile [Formula: see text] were inversely associated with POAF. Adjusting for age, heart failure (HF), and history of atrial fibrillation, the composite pre-operative (adrenergic) plasma marker [Formula: see text] was associated with a 4-fold increased occurrence of POAF (adjusted p = 0.0001). No association between plasma MAO-B and POAF was observed. CONCLUSIONS: Our results suggest that pre-operative adrenergic tone is an important factor underlying POAF. This information provides evidence that assessment of plasma catecholamines may be a low-cost method that is easy to implement for predicting which patients are likely to develop POAF. More investigation in a multicentric setting is needed to validate our results.

A BMI >35 does not protect patients undergoing cardiac bypass surgery from red blood cell transfusion.

The effect of obesity on allogeneic intraoperative blood product transfusion in patients undergoing coronary artery bypass graft surgery (CABG) is poorly understood. We analyzed the influence of obesity on the risk of intraoperative red blood cell (RBC) transfusion among 45,200 consecutive non-reoperative CABG procedures from a multi-institutional perfusion database. A body mass index (BMI) in obese I category was associated with a 9.9% decrease in transfusion risk (p<0.05). Compared to patients with a normal BMI, obese I and obese III patients do not have any change in the relative risk of RBC transfusion. Overweight and mild obesity have a protective role in reducing intraoperative blood transfusion during cardiopulmonary bypass (CPB) surgery. However, logistic regression analysis showed that much of the observed reduction in transfusion rates for obese patients can be accounted for by other known confounds. The lack of a linear effect of increasing BMI on blood transfusion risk is a novel finding and warrants further investigation.

Long-Term Survival after Cardiac Surgery in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although many patients with chronic obstructive pulmonary disease (COPD) require a prolonged length of stay (PLOS) following coronary artery bypass grafting (CABG), the impact of PLOS on long-term survival has not been examined in this population. OBJECTIVES: To determine the association between PLOS and long-term survival among COPD and non-COPD patients after CABG and to examine consequent policy and practice-based implications. METHODS: A retrospective cohort study of CABG patients was conducted between 2002 and 2011. Long-term survival was compared in patients with and without COPD and stratified by PLOS. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 203 patients (4.2%) had PLOS after nonemergent CABG (N = 4801). PLOS was an important independent predictor of decreased long-term survival (no COPD, no PLOS: HR = 1.0; COPD, no PLOS: adjusted HR [95% CI], 1.8 [1.5-2.1]; no COPD, PLOS: 3.3 [2.5-4.4]; COPD, PLOS: 6.0 [4.4-8.2]; PTrend < .001). CONCLUSIONS: COPD and PLOS are 2 of many factors that affect long-term mortality in postoperative CABG patients. Aggressive treatment strategies aimed at early weaning off of mechanical ventilation and prevention of reintubation among COPD patients must be considered carefully as a means to reduce length of stay after CABG. Our results also have important implications for the long-term management of these patients and strategies for containing costs over the life course of the patient.

Seasonal Incidence of Emergent Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Emergent coronary artery bypass grafting (CABG) surgery is often required in the case of severe coronary artery disease, which is refractory to traditional management. The objective of our study was to test the hypothesis that there is seasonal variation in the incidence of emergent CABG. METHODS: A sinusoidal logistic regression model was used to analyze operative data at our cardiovascular institute of 270 cases spanning 5939 calendar days. RESULTS: A cyclic peak risk for emergent CABG was observed for late winter (calendar day 66; P = .036). The odds ratios for the 1-, 2- and 3-month window surrounding this peak were 1.8 (95% CI = 0.94-3.5, P = .072), 1.6 (95% CI = 1.06-2.5, P = .024) and 1.4 (95% CI = 0.9-1.8, P = .066), respectively. CONCLUSION: Our results suggest that a seasonal variation may exist in the incidence of patients presenting with severe coronary artery disease requiring emergent CABG. This information is useful in the scheduling of hospital resources and staff. It also provides important etiology clues underlying coronary artery disease that may lead to future interventions or targeted therapies.

Comparison of Risk of Atrial Fibrillation in Black Versus White Patients After Coronary Artery Bypass Grafting.

Obesity has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). However, no studies have addressed the influence of race on this association. A total of 13,594 patients undergoing first-time, isolated CABG without preoperative AF between 1992 and 2011 were included in our study. The association between body mass index and POAF was compared by race. Relative risk and 95% CIs were computed using maximum likelihood log-binomial regression. Increasing levels of body mass index were associated with higher POAF risk after CABG in black but not white patients (pinteraction = 0.0009).

Conditional long-term survival following minimally invasive robotic mitral valve repair: a health services perspective.

BACKGROUND: Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to compute conditional survival in patients who received a robotically assisted, minimally invasive mitral valve repair procedure (RMVP). METHODS: Patients who received RMVP with annuloplasty band from May 2000 through April 2011 were included. A 5- and 10-year conditional survival model was computed using a multivariable product-limit method. RESULTS: Non-smoking men (≤65 years) who presented in sinus rhythm had a 96% probability of surviving at least 10 years if they survived their first year following surgery. In contrast, recent female smokers (>65 years) with preoperative atrial fibrillation only had an 11% probability of surviving beyond 10 years if alive after one year post-surgery. CONCLUSIONS: In the context of an increasingly managed healthcare environment, conditional survival provides useful information for patients needing to make important treatment decisions, physicians seeking to select patients most likely to benefit long-term following RMVP, and hospital administrators needing to comparatively assess the life-course economic value of high-tech surgical procedures.

Corrigendum to "Obesity in a model of gpx4 haploinsufficiency uncovers a causal role for lipid-derived aldehydes in human metabolic disease and cardiomyopathy" [Mol Metab 4 (6) (2015) 493-506].

[This corrects the article DOI: 10.1016/j.molmet.2015.04.001.].

Increased Long-Term Mortality among Black CABG Patients Receiving Preoperative Inotropic Agents.

The aim of this study was to examine racial differences in long-term mortality after coronary artery bypass grafting (CABG), stratified by preoperative use of inotropic agents. Black and white patients who required preoperative inotropic support prior to undergoing CABG procedures between 1992 and 2011 were compared. Mortality probabilities were computed using the Kaplan-Meier product-limit method. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 15,765 patients underwent CABG, of whom 211 received preoperative inotropic agents within 48 hours of surgery. Long-term mortality differed by race (black versus white) among preoperative inotropic category (inotropes: adjusted HR = 1.6, 95% CI = 1.009-2.4; no inotropes: adjusted HR = 1.15, 95% CI = 1.08-1.2; P(interaction) < 0.0001). Our study identified an independent preoperative risk-factor for long-term mortality among blacks receiving CABG. This outcome provides information that may be useful for surgeons, primary care providers, and their patients.

Obesity in a model of gpx4 haploinsufficiency uncovers a causal role for lipid-derived aldehydes in human metabolic disease and cardiomyopathy.

OBJECTIVE: Lipid peroxides and their reactive aldehyde derivatives (LPPs) have been linked to obesity-related pathologies, but whether they have a causal role has remained unclear. Glutathione peroxidase 4 (GPx4) is a selenoenzyme that selectively neutralizes lipid hydroperoxides, and human gpx4 gene variants have been associated with obesity and cardiovascular disease in epidemiological studies. This study tested the hypothesis that LPPs underlie cardio-metabolic derangements in obesity using a high fat, high sucrose (HFHS) diet in gpx4 haploinsufficient mice (GPx4(+/-)) and in samples of human myocardium. METHODS: Wild-type (WT) and GPx4(+/-) mice were fed either a standard chow (CNTL) or HFHS diet for 24 weeks, with metabolic and cardiovascular parameters measured throughout. Biochemical and immuno-histological analysis was performed in heart and liver at termination of study, and mitochondrial function was analyzed in heart. Biochemical analysis was also performed on samples of human atrial myocardium from a cohort of 103 patients undergoing elective heart surgery. RESULTS: Following HFHS diet, WT mice displayed moderate increases in 4-hydroxynonenal (HNE)-adducts and carbonyl stress, and a 1.5-fold increase in GPx4 enzyme in both liver and heart, while gpx4 haploinsufficient (GPx4(+/-)) mice had marked carbonyl stress in these organs accompanied by exacerbated glucose intolerance, dyslipidemia, and liver steatosis. Although normotensive, cardiac hypertrophy was evident with obesity, and cardiac fibrosis more pronounced in obese GPx4(+/-) mice. Mitochondrial dysfunction manifesting as decreased fat oxidation capacity and increased reactive oxygen species was also present in obese GPx4(+/-) but not WT hearts, along with up-regulation of pro-inflammatory and pro-fibrotic genes. Patients with diabetes and hyperglycemia exhibited significantly less GPx4 enzyme and greater HNE-adducts in their hearts, compared with age-matched non-diabetic patients. CONCLUSION: These findings suggest LPPs are key factors underlying cardio-metabolic derangements that occur with obesity and that GPx4 serves a critical role as an adaptive countermeasure.

Increased coronary artery disease severity in black women undergoing coronary bypass surgery.

Race and sex disparities are believed to play an important role in heart disease. The purpose of this study was to examine the association between race, sex, and number of diseased vessels at the time of coronary artery bypass grafting (CABG), and subsequent postoperative outcomes. The 13,774 patients undergoing first-time, isolated CABG between 1992 and 2011 were included. Trend in the number of diseased vessels between black and white patients, stratified by sex, were analyzed using a Cochran-Armitage trend test. Models were adjusted for age, procedural status (elective vs. nonelective), and payor type (private vs. nonprivate insurance). Black female CABG patients presented with an increasingly greater number of diseased vessels than white female CABG patients (adjusted P(trend) = 0.0021). A similar trend was not observed between black and white male CABG patients (adjusted P(trend) = 0.18). Black female CABG patients were also more likely to have longer intensive care unit and hospital lengths of stay than other race-sex groups.Our findings suggest that black female CABG patients have more advanced coronary artery disease than white female CABG patients. Further research is needed to determine the benefit of targeted preventive care and preoperative workup for this high-risk group.

Discharge ß-Blocker Use and Race after Coronary Artery Bypass Grafting.

INTRODUCTION: The use of discharge ß-blockers after cardiac surgery is associated with a long-term mortality benefit. ß-Blockers have been suggested to be less effective in black cardiovascular patients compared with whites. To date, racial differences in the long-term survival of coronary artery bypass grafting (CABG) patients who receive ß-blockers at discharge have not been examined. METHODS: A retrospective cohort study was conducted on patients undergoing CABG between 2002 and 2011. Long-term survival was compared in patients who were and who were not discharged with ß-blockers. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. P-for-interaction between race and discharge ß-blocker use was computed using a likelihood ratio test. RESULTS: A total of 853 (88%) black (n = 970) and 3,038 (88%) white (n = 3,460) patients had a history of ß-blocker use at discharge (N = 4,430). Black patients who received ß-blockers survived longer than those not receiving ß-blockers and the survival advantage was comparable with white patients (black, adjusted HR = 0.33, 95% CI = 0.23-0.46; white, adjusted HR = 0.48, 95% CI = 0.39-0.58; p-for-interaction = 0.74). Among patients discharged on ß-blockers, we did not observe a long-term survival advantage for white compared with black patients (HR = 1.2, 95% CI = 0.95-1.5). CONCLUSION: ß-Blocker use at discharge was associated with a survival advantage among black patients after CABG and a similar association was observed in white patients.

Risk-adjusted survival after coronary artery bypass grafting: implications for quality improvement.

Mortality represents an important outcome measure following coronary artery bypass grafting. Shorter survival times may reflect poor surgical quality and an increased number of costly postoperative complications. Quality control efforts aimed at increasing survival times may be misleading if not properly adjusted for case-mix severity. This paper demonstrates how to construct and cross-validate efficiency-outcome plots for a specified time (e.g., 6-month and 1-year survival) after coronary artery bypass grafting, accounting for baseline cardiovascular risk factors. The application of this approach to regional centers allows for the localization of risk stratification rather than applying overly broad and non-specific models to their patient populations.

Conditional survival of heart failure patients after coronary artery bypass grafting.

AIMS: Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to estimate conditional survival in heart failure patients after coronary artery bypass grafting (CABG). METHODS: Heart failure patients with multivessel coronary artery disease undergoing first-time, isolated CABG between 1992 and 2011 were included in this study. Conditional survival estimates were computed for 1, 5, and 10 years after already surviving 0.5, 1, 2, 3, 4, and 5 years. RESULTS: Compared with traditional survival estimates, conditional survival was consistently higher at all time periods. The overall 2-year adjusted survival estimate was 84% compared with the 1-year conditional survival rate of 95% for 1-year survivors. Similarly, the overall 10-year adjusted survival rate was 36% from the time of surgery compared with the 5-year conditional survival of 54% for patients who had survived 5 years. CONCLUSION: Conditional survival provides a more accurate estimate of long-term survival in heart failure patients who have already survived for a certain amount of time after CABG. This information is useful for patients and physicians who manage their long-term care.

Seasonal incidence of hospital admissions for Stanford type A aortic dissection.

The objective of this study was to test the hypothesis that there is seasonal variation in the incidence of Stanford type A aortic dissection (SA-AoD) among patients admitted to our cardiovascular surgical service. A sinusoidal logistic regression model was used to analyze event data for 6081 calendar days. A cyclic peak risk for SA-AoD was observed for calendar day 304 (p=0.019). The odds ratios for the 3- and 6-month window surrounding this peak were 1.6 (p=0.054) and 1.7 (p=0.0040), respectively. Our results suggest than a seasonal variation exists in the incidence of SA-AoD.

Operative status and survival after coronary artery bypass grafting.

BACKGROUND: The effect of race on long-term survival of patients undergoing elective and nonelective coronary artery bypass grafting (CABG) is currently unknown. The purpose of this study was to compare long-term survival between black and white CABG patients by operative status. METHODS: Long-term survival of black versus white patients undergoing elective and nonelective CABG procedures between 1992 and 2011 was compared. Survival probabilities were computed using the Kaplan-Meier product-limit method and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 13,774 patients were included in this study. The median follow-up time for study participants was 8.2 years. Black patients undergoing elective CABG died sooner than whites (adjusted HR = 1.4, 95% CI = 1.2-1.5). Survival was similar between blacks and whites in the nonelective population (adjusted HR = 1.0, 95% CI = 0.96-1.1). CONCLUSIONS: Black race was a statistically significant predictor of long-term survival after elective but not nonelective CABG.

Do fish oil omega-3 fatty acids enhance antioxidant capacity and mitochondrial fatty acid oxidation in human atrial myocardium via PPARγ activation?

Abstract Studies in experimental models suggest that n-3 polyunsaturated fatty acids (PUFAs) improve metabolic and anti-inflammatory/antioxidant capacity of the heart, although the mechanisms are unclear and translational evidence is lacking. In this study, patients ingested a moderately high dose of n-3 PUFAs (3.4 g/day eicosapentaenoic (EPA) and doxosahexaenoic acid (DHA) ethyl-esters) for a period of 2-3 weeks before having elective cardiac surgery. Blood was obtained before treatment and at the time of surgery, and myocardial tissue from the right atrium was also dissected during surgery. Blood EPA levels increased and myocardial tissue EPA and DHA levels were significantly higher in n-3 PUFA-treated patients compared with untreated, standard-of-care control patients. Interestingly, n-3 PUFA patients had greater nuclear transactivation of peroxisome proliferator-activated receptor-γ (PPARγ), fatty acid metabolic gene expression, and enhanced mitochondrial respiration supported by palmitoyl-carnitine in the atrial myocardium, despite no difference in mitochondrial content. Myocardial tissue from n-3 PUFA patients also displayed greater expression and activity of key antioxidant/anti-inflammatory enzymes. These findings lead to our hypothesis that PPARγ activation is a mechanism by which fish oil n-3 PUFAs enhance mitochondrial fatty acid oxidation and antioxidant capacity in human atrial myocardium, and that this preoperative therapeutic regimen may be optimal for mitigating oxidative/inflammatory stress associated with cardiac surgery.

Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation.

BACKGROUND: Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high-risk patients, remains elusive. METHODS AND RESULTS: Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH-peroxidase (GPx) and GSH-reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10-fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. CONCLUSIONS: Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis.