Immediate impact of coronary artery bypass graft surgery on regional myocardial perfusion: Results from the Collaborative Pilot Study to Determine the Correlation Between Intraoperative Observations Using Spy Near-Infrared Imaging and Cardiac Catheterization Laboratory Physiological Assessment of Lesion Severity.

Objectives: Coronary artery bypass grafting (CABG) is performed using anatomic guidance. Data connecting the physiologic significance of the coronary vessel stenosis to the acute physiologic response to grafting are lacking. The Collaborative Pilot Study to Determine the Correlation Between Intraoperative Observations Using Spy Near-Infrared Imaging and Cardiac Catheterization Laboratory Physiological Assessment of Lesion Severity study is the first to compare preintervention coronary physiology with the acute regional myocardial perfusion change (RMP-QC) at CABG in a per-graft analysis. Methods: Non-emergent patients undergoing diagnostic catheterization suitable for multivessel CABG were enrolled. Synergy between Percutaneous Coronary Intervention with Taxus score, fractional flow reserve (FFR), instantaneous wave free ratio (iFR), and quantitative coronary angiography was documented in 75 epicardial coronary arteries, with 62 angiographically intermediate and 13 severe stenoses. At CABG, near-infrared fluorescence analysis quantified the relative change (post- vs pregrafting, termed RMP-QC) in the grafted vessel's perfusion territory. Scatter plots were constructed for RMP-QC versus quantitative coronary angiography and RMP-QC versus FFR/iFR. Exact quadrant randomization test for randomness was used. Results: There was no relationship between RMP-QC and quantitative coronary angiography percent diameter stenosis, whether all study vessels were included (P = .949) or vessels with core-lab quantitative coronary angiography only (P = .922). A significant nonrandom association between RMP-QC and FFR (P = .025), as well as between RMP-QC and iFR (P = .008), was documented. These associations remained when excluding vessels with assigned FFR and iFR values (P = .0092 and P = .0006 for FFR and iFR, respectively). Conclusions: The Collaborative Pilot Study to Determine the Correlation Between Intraoperative Observations Using Spy Near-Infrared Imaging and Cardiac Catheterization Laboratory Physiological Assessment of Lesion Severity study demonstrates there is no association between angiographic coronary stenosis severity and the acute perfusion change after grafting; there is an association between functional stenosis severity and absolute increase in regional myocardial perfusion after CABG.

International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial: Rationale and design.

BACKGROUND: Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia. METHODS: The ISCHEMIA trial is a National Heart, Lung, and Blood Institute supported trial, designed to compare an initial invasive or conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing. Five thousand one-hundred seventy-nine participants have been randomized. Key exclusion criteria included estimated glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline. Most enrolled participants with normal renal function first underwent blinded coronary computed tomography angiography (CCTA) to exclude those with left main coronary artery disease (CAD) and without obstructive CAD. All randomized participants receive secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy undergo cardiac catheterization only for failure of OMT. The primary endpoint is a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest. Assuming the primary endpoint will occur in 16% of the conservative group within 4 years, estimated power exceeds 80% to detect an 18.5% reduction in the primary endpoint. Major secondary endpoints include the composite of CV death and nonfatal MI, net clinical benefit (primary and secondary endpoints combined with stroke), angina-related symptoms and disease-specific quality of life, as well as a cost-effectiveness assessment in North American participants. Ancillary studies of patients with advanced chronic kidney disease and those with documented ischemia and non-obstructive coronary artery disease are being conducted concurrently. CONCLUSIONS: ISCHEMIA will provide new scientific evidence regarding whether an invasive management strategy improves clinical outcomes when added to optimal medical therapy in patients with SIHD and moderate or severe ischemia.

Angiotensin Receptor Blockade Improves Cardiac Surgical Outcomes in Patients With Metabolic Syndrome.

BACKGROUND: Perioperative use of angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEis) in patients undergoing cardiac operations remains controversial. The current practice of discontinuing renin-angiotensin-system inhibitors preoperatively may negate their beneficial effects in vulnerable populations, including patients with metabolic syndrome, who exhibit elevated renin-angiotensin system activity. We hypothesized that preoperative ARB use is associated with reduced incidence of postoperative complications, compared with ACEi or no drug, in patients with metabolic syndrome undergoing coronary artery bypass grafting. METHODS: We used propensity matching to derive a cohort of 1,351 patients from 2,998 who underwent coronary artery bypass grafting based on preoperative use of ARBs, ACEis, or no renin-angiotensin-system inhibitors. Our primary end point was a composite of adverse events occurring within 30 days after the operation: new-onset atrial fibrillation/flutter, arrhythmia requiring cardioversion, perioperative myocardial infarction, acute renal failure, need for dialysis, cerebrovascular accidents, acute respiratory failure, or perioperative death. RESULTS: At least one adverse event occurred in 524 (38.8%) of matched cohort patients (1,184 [39.6% of all patients]). Adjusting for European System for Cardiac Operative Risk Evaluation and metabolic syndrome in the matched cohort, preoperative use of ARBs was associated with a lower incidence of adverse events in patients with metabolic syndrome compared with preoperative use of no renin-angiotensin-system inhibitors (odds ratio, 0.43; 95% confidence interval, 0.19 to 0.99) or ACEis (odds ratio, 0.38; 95% confidence interval, 0.16 to 0.88). CONCLUSIONS: Preoperative use of ARBs, but not ACEis, confers a benefit within 30 days after cardiac operations in patients with metabolic syndrome, suggesting potential efficacy differences of these drug classes in reducing cardiovascular morbidity and death in ambulatory vs surgical patients.

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.

Noninvasive Quantification of Blood Flow in Epicardial Coronary Arteries, Coronary Artery Bypass Grafts, and Anastomoses.

OBJECTIVE: Direct flow measurement in native epicardial coronary arteries, bypass conduits, and anastomoses is severely limited by the invasiveness and inaccuracy of existing technologies. As a result, less than 25% of patients undergoing coronary artery bypass grafting (CABG) worldwide have any intraoperative evaluation performed. A simple, accurate, and noninvasive technology to directly quantify blood flow and rheology surrounding anastomotic sites is a critical unmet need in CABG. METHODS: Existing technology limitations drove development of a different technology solution. With an optical physics approach, flow in conduits and tissue can be quantified in real time with nonionizing broad-spectrum imaging as well as temporal and spatial analyses. Cardiac motion, calibration, and combining anatomy + physiology in imaging were challenges requiring solutions. RESULTS: This patented imaging technology was developed and tested in an established porcine cardiac experimental model and in clinical proof-of-concept studies. Flow velocities and flows in epicardial coronary arteries vary physiologically with the cardiac cycle and with acute ischemia, as predicted by previous studies using traditional technologies. Imaging data are captured from a 30-cm viewing distance, analyzed and displayed in real time as a video. The field of view enables capture of flow in the proximal and distal epicardial coronary, the conduit, at the anastomosis and in the distal myocardium simultaneously. CONCLUSIONS: Rheologic flow interaction between conduit and native coronary at the anastomosis remains the most poorly understood technical aspect of CABG. A noninvasive, noncontact, no-risk imaging technology as simple as a snapshot can provide this critical physiologic information, validate and document intraoperative quality, and improve even further CABG outcomes.

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.

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.

Improving quality and outcomes of coronary artery bypass grafting procedures.

The evolution in the approach, clinical care and outcomes of ischemic heart disease, has been dramatic over the past decade. Optimizing medical therapy initially and throughout the care delivery process has been transformative. The addition of new physiologic data to the traditional anatomic framework for diagnosis and therapy of more extensive stable ischemic heart disease (SIHD) enables quality and outcomes improvements in this patient population overall and in the patient subsets of acute coronary syndrome and SIHD. In patients undergoing coronary artery bypass grafting (CABG), these developments have changed the objective goal of surgical revascularization over this time interval. This review discusses the opportunities for quality and outcomes improvement in CABG, in the context of SIHD overall.

Frequency and Predictors of Internal Mammary Artery Graft Failure and Subsequent Clinical Outcomes: Insights From the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV Trial.

BACKGROUND: The internal mammary artery (IMA) is the preferred conduit for bypassing the left anterior descending (LAD) artery in patients undergoing coronary artery bypass grafting. Systematic evaluation of the frequency and predictors of IMA failure and long-term outcomes is lacking. METHODS AND RESULTS: The Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV trial participants who underwent IMA-LAD revascularization and had 12- to 18-month angiographic follow-up (n=1539) were included. Logistic regression with fast false selection rate methods was used to identify characteristics associated with IMA failure (≥75% stenosis). The relationship between IMA failure and long-term outcomes, including death, myocardial infarction, and repeat revascularization, was assessed with Cox regression. IMA failure occurred in 132 participants (8.6%). Predictors of IMA graft failure were LAD stenosis <75% (odds ratio, 1.76; 95% confidence interval, 1.19-2.59), additional bypass graft to diagonal branch (odds ratio, 1.92; 95% confidence interval, 1.33-2.76), and not having diabetes mellitus (odds ratio, 1.82; 95% confidence interval, 1.20-2.78). LAD stenosis and additional diagonal graft remained predictive of IMA failure in an alternative model that included angiographic failure or death before angiography as the outcome. IMA failure was associated with a significantly higher incidence of subsequent acute (<14 days of angiography) clinical events, mostly as a result of a higher rate of repeat revascularization. CONCLUSIONS: IMA failure was common and associated with higher rates of repeat revascularization, and patients with intermediate LAD stenosis or with an additional bypass graft to the diagonal branch had increased risk for IMA failure. These findings raise concerns about competitive flow and the benefit of coronary artery bypass grafting in intermediate LAD stenosis without functional evidence of ischemia. CLINICAL TRIAL REGISTRATION: URL: http:/www.clinicaltrials.gov. Unique identifier: NCT00042081.

Medical Therapy With Versus Without Revascularization in Stable Patients With Moderate and Severe Ischemia: The Case for Community Equipoise.

All patients with stable ischemic heart disease (SIHD) should be managed with guideline-directed medical therapy (GDMT), which reduces progression of atherosclerosis and prevents coronary thrombosis. Revascularization is also indicated in patients with SIHD and progressive or refractory symptoms, despite medical management. Whether a strategy of routine revascularization (with percutaneous coronary intervention or coronary artery bypass graft surgery as appropriate) plus GDMT reduces rates of death or myocardial infarction, or improves quality of life compared to an initial approach of GDMT alone in patients with substantial ischemia is uncertain. Opinions run strongly on both sides, and evidence may be used to support either approach. Careful review of the data demonstrates the limitations of our current knowledge, resulting in a state of community equipoise. The ongoing ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) is being performed to determine the optimal approach to managing patients with SIHD, moderate-to-severe ischemia, and symptoms that can be controlled medically. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

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.

Long-term clinical and angiographic outcomes in patients with diabetes undergoing coronary artery bypass graft surgery: results from the Project of Ex-vivo Vein Graft Engineering via Transfection IV trial.

BACKGROUND: There is limited information about the association between diabetes, its treatment, and long-term angiographic and clinical outcomes in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the association of diabetes and its treatment with 1-year angiographic graft failure and 5-year clinical outcomes in patients undergoing CABG. METHODS: Using data from 3,014 patients in PREVENT IV, we analyzed angiographic and clinical outcomes in patients with and without diabetes and among those who did and did not receive insulin before CABG. Logistic regression and Cox proportional hazards models were used to adjust for differences in baseline variables. RESULTS: Overall, 1,139 (37.8%) patients had diabetes. Of these, 305 (26.8%) received insulin. One-year rates of vein graft failure were similar in patients with and without diabetes but, among diabetics, tended to be higher in patients who received insulin compared with those who did not. At 5 years, rates of death, myocardial infarction, or revascularization were higher among patients with compared with those without diabetes (adjusted hazard ratio 1.57; 95% CI 1.26-1.96; P < .001) and, among diabetics, higher among those who received insulin (adjusted hazard ratio 1.15; 95% CI 1.02-1.30; P = .02). CONCLUSIONS: Patients with diabetes had similar rates of vein graft failure but worse clinical outcomes than patients without diabetes. Patients who received insulin had significantly worse clinical outcomes than patients who did not receive insulin. Further studies to better understand the mechanism behind these findings and to improve the outcomes of patients with insulin-requiring diabetes undergoing CABG surgery are warranted.

Readmissions after cardiac surgery: experience of the National Institutes of Health/Canadian Institutes of Health research cardiothoracic surgical trials network.

BACKGROUND: Readmissions are a common problem in cardiac surgery. The goal of this study was to examine the frequency, timing, and associated risk factors for readmission after cardiac operations. METHODS: A 10-center cohort study prospectively enrolled 5,158 adult cardiac surgical patients (5,059 included in analysis) to assess risk factors for infection after cardiac operations. Data were also collected on all-cause readmissions occurring within 65 days after the operation. Major outcomes included the readmission rate stratified by procedure type, cause of readmission, length of readmission stay, and discharge disposition after readmission. Multivariable Cox regression was used to determine risk factors for time to first readmission. RESULTS: The overall rate of readmission was 18.7% (number of readmissions, 945). When stratified by the most common procedure type, readmission rates were isolated coronary artery bypass grafting, 14.9% (n = 248); isolated valve, 18.3% (n = 337); and coronary artery bypass grafting plus valve, 25.0% (n = 169). The three most common causes of first readmission within 30 days were infection (17.1% [n = 115]), arrhythmia (17.1% [n = 115]), and volume overload (13.5% [n = 91]). More first readmissions occurred within 30 days (80.6% [n = 672]) than after 30 days (19.4% [n = 162]), and 50% of patients were readmitted within 22 days from the index operation. The median length of stay during the first readmission was 5 days. Discharge in 15.8% of readmitted patients (n = 128) was to a location other than home. Baseline patient characteristics associated with readmission included female gender, diabetes mellitus on medication, chronic obstructive pulmonary disease, elevated creatinine, lower hemoglobin, and longer operation time. More complex surgical procedures were associated with an increased risk of readmission compared with the coronary artery bypass grafting group. CONCLUSIONS: Nearly 1 of 5 patients who undergo cardiac operations require readmission, an outcome with significant health and economic implications. Management practices to avert in-hospital infections, reduce postoperative arrhythmias, and avoid volume overload offer important targets for quality improvement.