Impact of Oral Anticoagulation on Clinical Outcomes in Postoperative Atrial Fibrillation.

INTRODUCTION: The impact of postoperative oral anticoagulation (OAC) with warfarin on postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) was the focus of this examination of patients from the randomized endo-vein graft prospective (REGROUP) Trial. MATERIAL AND METHODS: REGROUP was a prospective randomized Veterans Affairs cooperative study comparing endoscopic versus open vein harvest in elective CABG patients (March 2014-April 2017) at 16 Veterans Affairs facilities. This study compared new-onset POAF patients who were treated with warfarin versus no-warfarin. Outcomes included stroke during active follow-up and a major adverse cardiac event composite of mortality, acute myocardial infarction, and repeat revascularization during active and passive follow-up. RESULTS: Of the 316/1103 (28.6%) of REGROUP patients who developed new-onset POAF, 45 patients were excluded - mainly for preoperative warfarin use. Of the remaining 269 patients, 85 received OAC with warfarin (OAC group); 184 did not (no-OAC group). Stroke rates during active follow-up (32 [IQR 24-38] mo) were 3.5% OAC group versus 5.4% no-OAC group (P = 0.76); major adverse cardiac eventrates were 20% OAC versus 11.4% no-OAC (P = 0.06). On longer follow-up of (median 4.61 [IQR 3.9-5.1] y), discharge OAC use was associated with all-cause mortality after adjusting for Society of Thoracic Surgeons mortality risk (20.0% versus 11.4% no-OAC use; HR = 2.00, 95% CI: 1.05-3.81, P = 0.035). CONCLUSIONS: REGROUP patients with POAF treated with OAC had similar stroke and higher mortality rates versus no-OAC patients. Further investigation of the risk-benefit ratio of OAC in post-CABG patients and which POAF patient subgroups might derive the most benefit with anticoagulation appears warranted.

Nurse and Social Worker Palliative Telecare Team and Quality of Life in Patients With COPD, Heart Failure, or Interstitial Lung Disease: The ADAPT Randomized Clinical Trial.

Importance: Many patients with chronic obstructive pulmonary disease (COPD), heart failure (HF), and interstitial lung disease (ILD) endure poor quality of life despite conventional therapy. Palliative care approaches may benefit this population prior to end of life. Objective: Determine the effect of a nurse and social worker palliative telecare team on quality of life in outpatients with COPD, HF, or ILD compared with usual care. Design, Setting, and Participants: Single-blind, 2-group, multisite randomized clinical trial with accrual between October 27, 2016, and April 2, 2020, in 2 Veterans Administration health care systems (Colorado and Washington), and including community-based outpatient clinics. Outpatients with COPD, HF, or ILD at high risk of hospitalization or death who reported poor quality of life participated. Intervention: The intervention involved 6 phone calls with a nurse to help with symptom management and 6 phone calls with a social worker to provide psychosocial care. The nurse and social worker met weekly with a study primary care and palliative care physician and as needed, a pulmonologist, and cardiologist. Usual care included an educational handout developed for the study that outlined self-care for COPD, ILD, or HF. Patients in both groups received care at the discretion of their clinicians, which could include care from nurses and social workers, and specialists in cardiology, pulmonology, palliative care, and mental health. Main Outcomes and Measures: The primary outcome was difference in change in quality of life from baseline to 6 months between the intervention and usual care groups (FACT-G score range, 0-100, with higher scores indicating better quality of life, clinically meaningful change ≥4 points). Secondary quality-of-life outcomes at 6 months included disease-specific health status (Clinical COPD Questionnaire; Kansas City Cardiomyopathy Questionnaire-12), depression (Patient Health Questionnaire-8) and anxiety (Generalized Anxiety Disorder-7) symptoms. Results: Among 306 randomized patients (mean [SD] age, 68.9 [7.7] years; 276 male [90.2%], 30 female [9.8%]; 245 White [80.1%]), 177 (57.8%) had COPD, 67 (21.9%) HF, 49 (16%) both COPD and HF, and 13 (4.2%) ILD. Baseline FACT-G scores were similar (intervention, 52.9; usual care, 52.7). FACT-G completion was 76% (intervention, 117 of 154; usual care, 116 of 152) at 6 months for both groups. Mean (SD) length of intervention was 115.1 (33.4) days and included a mean of 10.4 (3.3) intervention calls per patient. In the intervention group, 112 of 154 (73%) patients received the intervention as randomized. At 6 months, mean FACT-G score improved 6.0 points in the intervention group and 1.4 points in the usual care group (difference, 4.6 points [95% CI, 1.8-7.4]; P = .001; standardized mean difference, 0.41). The intervention also improved COPD health status (standardized mean difference, 0.44; P = .04), HF health status (standardized mean difference, 0.41; P = .01), depression (standardized mean difference, -0.50; P < .001), and anxiety (standardized mean difference, -0.51; P < .001) at 6 months. Conclusions and Relevance: For adults with COPD, HF, or ILD who were at high risk of death and had poor quality of life, a nurse and social worker palliative telecare team produced clinically meaningful improvements in quality of life at 6 months compared with usual care. Trial Registration: ClinicalTrials.gov Identifier: NCT02713347.

Randomized Trial of Endoscopic or Open Vein-Graft Harvesting for Coronary-Artery Bypass.

BACKGROUND: The saphenous-vein graft is the most common conduit for coronary-artery bypass grafting (CABG). The influence of the vein-graft harvesting technique on long-term clinical outcomes has not been well characterized. METHODS: We randomly assigned patients undergoing CABG at 16 Veterans Affairs cardiac surgery centers to either open or endoscopic vein-graft harvesting. The primary outcome was a composite of major adverse cardiac events, including death from any cause, nonfatal myocardial infarction, and repeat revascularization. Leg-wound complications were also evaluated. RESULTS: A total of 1150 patients underwent randomization. Over a median follow-up of 2.78 years, the primary outcome occurred in 89 patients (15.5%) in the open-harvest group and 80 patients (13.9%) in the endoscopic-harvest group (hazard ratio, 1.12; 95% confidence interval [CI], 0.83 to 1.51; P=0.47). A total of 46 patients (8.0%) in the open-harvest group and 37 patients (6.4%) in the endoscopic-harvest group died (hazard ratio, 1.25; 95% CI, 0.81 to 1.92); myocardial infarctions occurred in 34 patients (5.9%) in the open-harvest group and 27 patients (4.7%) in the endoscopic-harvest group (hazard ratio, 1.27; 95% CI, 0.77 to 2.11), and revascularization occurred in 35 patients (6.1%) in the open-harvest group and 31 patients (5.4%) in the endoscopic-harvest group (hazard ratio, 1.14; 95% CI, 0.70 to 1.85). Leg-wound infections occurred in 18 patients (3.1%) in the open-harvest group and in 8 patients (1.4%) in the endoscopic-harvest group (relative risk, 2.26; 95% CI, 0.99 to 5.15). CONCLUSIONS: Among patients undergoing CABG, we did not find a significant difference between open vein-graft harvesting and endoscopic vein-graft harvesting in the risk of major adverse cardiac events. (Funded by the Cooperative Studies Program, Office of Research and Development, Department of Veterans Affairs; REGROUP ClinicalTrials.gov number, NCT01850082 .).

Health-related quality of life impacts upon 5-year survival after coronary artery bypass surgery.

BACKGROUND: Poor preoperative health-related quality of life (HRQoL) has been associated with reduced short-term survival after coronary artery bypass graft (CABG) surgery; however, its impact on long-term mortality is unknown. This study's objective was to determine if baseline HRQoL status predicts 5-year post-CABG mortality. METHODS: This prespecified, randomized on/off bypass follow-up study (ROOBY-FS) subanalysis compared baseline patient characteristics and HRQoL scores, obtained from the Seattle Angina Questionnaire (SAQ) and Veterans RAND Short Form-36 (VR-36), between 5-year post-CABG survivors and nonsurvivors. Standardized subscores were calculated for each questionnaire. Multivariable logistic regression assessed whether HRQoL survey subcomponents independently predicted 5-year mortality (p ≤ .05). RESULTS: Of the 2203 ROOBY-FS enrollees, 2104 (95.5%) completed baseline surveys. Significant differences between 5-year post-CABG deaths (n = 286) and survivors (n = 1818) included age, history of chronic obstructive pulmonary disease, stroke, peripheral vascular disease, renal dysfunction, diabetes, lower left ventricular ejection fraction, atrial fibrillation, depression, non-White race/ethnicity, lower education status, and off-pump CABG. Adjusting for these factors, baseline VR-36 physical component summary score (p = .01), VR-36 mental component summary score (p < .001), and SAQ physical limitation score (p = .003) were all associated with 5-year all-cause mortality. CONCLUSIONS: Pre-CABG HRQoL scores may provide clinically relevant prognostic information beyond traditional risk models and prove useful for patient-provider shared decision-making and enhancing pre-CABG informed consent.

Five-Year Outcomes after On-Pump and Off-Pump Coronary-Artery Bypass.

BACKGROUND: Coronary-artery bypass grafting (CABG) surgery may be performed either with cardiopulmonary bypass (on pump) or without cardiopulmonary bypass (off pump). We report the 5-year clinical outcomes in patients who had been included in the Veterans Affairs trial of on-pump versus off-pump CABG. METHODS: From February 2002 through June 2007, we randomly assigned 2203 patients at 18 medical centers to undergo either on-pump or off-pump CABG, with 1-year assessments completed by May 2008. The two primary 5-year outcomes were death from any cause and a composite outcome of major adverse cardiovascular events, defined as death from any cause, repeat revascularization (CABG or percutaneous coronary intervention), or nonfatal myocardial infarction. Secondary 5-year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction. Primary outcomes were assessed at a P value of 0.05 or less, and secondary outcomes at a P value of 0.01 or less. RESULTS: The rate of death at 5 years was 15.2% in the off-pump group versus 11.9% in the on-pump group (relative risk, 1.28; 95% confidence interval [CI], 1.03 to 1.58; P=0.02). The rate of major adverse cardiovascular events at 5 years was 31.0% in the off-pump group versus 27.1% in the on-pump group (relative risk, 1.14; 95% CI, 1.00 to 1.30; P=0.046). For the 5-year secondary outcomes, no significant differences were observed: for nonfatal myocardial infarction, the rate was 12.1% in the off-pump group and 9.6% in the on-pump group (P=0.05); for death from cardiac causes, the rate was 6.3% and 5.3%, respectively (P=0.29); for repeat revascularization, the rate was 13.1% and 11.9%, respectively (P=0.39); and for repeat CABG, the rate was 1.4% and 0.5%, respectively (P=0.02). CONCLUSIONS: In this randomized trial, off-pump CABG led to lower rates of 5-year survival and event-free survival than on-pump CABG. (Funded by the Department of Veterans Affairs Office of Research and Development Cooperative Studies Program and others; ROOBY-FS ClinicalTrials.gov number, NCT01924442 .).

Preoperative factors associated with worsening in health-related quality of life following coronary artery bypass grafting in the Randomized On/Off Bypass (ROOBY) trial.

For advanced coronary disease, coronary artery bypass graft (CABG) surgery generally improves patients' symptoms and long-term survival. Unfortunately, some patients experience worse health-related quality of life (HRQL) after CABG. The objective of this study is to report the frequency and risk factors associated with 1-year post-CABG HRQL deterioration. METHODS: From 2002 to 2007, 2203 "Randomized On/Off Bypass" (ROOBY) trial patients randomly received either off-pump or on-pump CABG at 18 VA medical centers. Subjects completed both baseline and 1-year Seattle Angina Questionnaire (SAQ) and the Veterans Rand 36 (VR-36) questionnaires to assess HRQL. Using previously published criteria, the rates of clinically significant changes were determined for the SAQ [angina frequency (AF), physical limitation (PL), and quality of life (QoL)] and VR36 [mental component score (MCS) and physical component score (PCS)] subscales. Multivariate regression models were then used to identify pre-CABG patient characteristics associated with worsened 1-year HRQL status for each subscale. RESULTS: Over 80% of patients had an improvement or no change in SAQ and VR-36 subscale scores 1 year after CABG. The HRQL scale-specific deterioration rates were 4.5% SAQ-AF, 16.8% SAQ-PL, 4.9% SAQ-QoL, 19.4% VR36-MCS, and 13.5% VR36-PCS. Predictors of 1-year HRQL deterioration were diabetes and smoking for the SAQ-AF; diabetes, chronic obstructive pulmonary disease (COPD), and peripheral vascular disease (PVD) for SAQ-PL; COPD and depression for the SAQ-QoL; diabetes for VR36-PCS, and history of stroke and depression for VR36-MCS. The baseline score was an independent predictor for worsening in all the subscales studied. CONCLUSIONS: Among VA patients, less than 20% experienced worse HRQL 1 year after CABG. For patients with low symptom burden at baseline, diabetes, smoking, depression, PVD, COPD, and a prior stroke, clinicians should be more cautious in pre-CABG counseling as to their anticipated HRQL improvements.

Concordance between administrative data and clinical review for mortality in the randomized on/off bypass follow-up study (ROOBY-FS).

BACKGROUND: The optimal methodology to identify cardiac versus non-cardiac cause of death following cardiac surgery has not been determined. METHODS: The Randomized On/Off Bypass Trial was a multicenter, randomized, controlled clinical trial of 2203 patients (February 2002-May 2008) comparing 1-year cardiac outcomes between off-pump and on-pump bypass surgery. In 2013, the Veterans Affairs (VA) Cooperative Studies Program funded a follow-up study to assess 5-year outcomes including mortality. Deaths were identified and confirmed using the National Death Index (NDI), VA Vital Status file, and medical records. An Endpoints Committee (EC) reviewed patient medical records and classified each cause of death as cardiac, non-cardiac, or unknown. Using pre-determined ICD-10 codes, NDI death certificates were independently used to classify deaths as cardiac or non-cardiac. Cause of death was compared between the NDI and EC classifications and concordance measured, using Kappa statistics. RESULTS: Of the 297 5-year deaths identified by the NDI and/or VA vital status file and confirmed by the EC, 219 had adequate patient records for EC cause of death determination. The EC adjudicated 141 of these deaths as non-cardiac and 78 as cardiac, while the NDI classified 150 as non-cardiac and 69 as cardiac; agreement was 77.6% (kappa 0.500; P < 0.001). CONCLUSIONS: Since concordance between EC and NDI cause of death classifications was only moderate, caution should be exercised in relying exclusively on NDI data to determine cause of death. A hybrid approach, integrating multiple information sources, may provide the most accurate approach to classifying cause of death.

Complete Coronary Revascularization and Outcomes in Patients Who Underwent Coronary Artery Bypass Grafting: Insights from The REGROUP Trial.

There is growing evidence in support of coronary complete revascularization (CR). Nonetheless, there is no universally accepted definition of CR in patients who undergo coronary bypass grafting surgery (CABG). We sought to investigate the outcomes of CR, defined as surgical revascularization of any territory supplied by a suitable coronary artery with ≥50% stenosis. We performed a preplanned subanalysis in the Randomized Trial of Endoscopic or Open Saphenous Vein Graft Harvesting (REGROUP) clinical trial cohort. Of 1,147 patients who underwent CABG, 810 (70.6%) received CR. The primary outcome was a composite of major adverse cardiac events (MACEs), including death from any cause, nonfatal myocardial infarction, or repeat revascularization over a median 4.7 years of follow-up. MACE occurred in 175 patients (21.6%) in the CR group and 86 patients (25.5%) in the incomplete revascularization (IR) group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.67 to 1.13, p = 0.29). A total of 97 patients (12.0%) in the CR group and 48 patients (14.2%) in the IR group died (HR 0.93, 95% CI 0.65 to 1.32, p = 0.67); nonfatal myocardial infarction occurred in 49 patients (6.0%) in the CR group and 30 patients (8.9%) in the IR group (HR 0.76, 95% CI 0.48 to 1.2, p = 0.24), and repeat revascularization occurred in 62 patients (7.7%) in the CR group and 39 patients (11.6%) in the IR group (HR 0.64; 95% CI 0.42 to 0.95, p = 0.027). In conclusion, in patients with a great burden of co-morbidities who underwent CABG in the REGROUP trial over a median follow-up period of a median 4.7 years, CR was associated with similar MACE rates but a reduced risk of repeat revascularization. Longer-term follow-up is warranted.

Off-Pump coronary artery bypass surgery is associated with worse arterial and saphenous vein graft patency and less effective revascularization: Results from the Veterans Affairs Randomized On/Off Bypass (ROOBY) trial.

BACKGROUND: The Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) trial compared clinical and angiographic outcomes in off-pump versus on-pump coronary artery bypass graft (CABG) surgery to ascertain the relative efficacy of the 2 techniques. METHODS AND RESULTS: From February 2002 to May 2007, the ROOBY trial randomized 2203 patients to off-pump versus on-pump CABG. Follow-up angiography was obtained in 685 off-pump (62%) and 685 on-pump (62%) patients. Angiograms were analyzed (blinded to treatment) for FitzGibbon classification (A=widely patent, B=flow limited, O=occluded) and effective revascularization. Effective revascularization was defined as follows: All 3 major coronary territories with significant disease were revascularized by a FitzGibbon A-quality graft to the major diseased artery, and there were no new postanastomotic lesions. Off-pump CABG resulted in lower FitzGibbon A patency rates than on-pump CABG for arterial conduits (85.8% versus 91.4%; P=0.003) and saphenous vein grafts (72.7% versus 80.4%; P<0.001). Fewer off-pump patients were effectively revascularized (50.1% versus 63.9% on-pump; P<0.001). Within each major coronary territory, effective revascularization was worse off pump than on pump (all P≤0.001). The 1-year adverse cardiac event rate was 16.4% in patients with ineffective revascularization versus 5.9% in patients with effective revascularization (P<0.001). CONCLUSIONS: Off-pump CABG resulted in significantly lower FitzGibbon A patency for arterial and saphenous vein graft conduits and less effective revascularization than on-pump CABG. At 1 year, patients with less effective revascularization had higher adverse event rates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00032630.

Patient-centered disease management (PCDM) for heart failure: study protocol for a randomised controlled trial.

BACKGROUND: Chronic heart failure (HF) disease management programs have reported inconsistent results and have not included comorbid depression management or specifically focused on improving patient-reported outcomes. The Patient Centered Disease Management (PCDM) trial was designed to test the effectiveness of collaborative care disease management in improving health status (symptoms, functioning, and quality of life) in patients with HF who reported poor HF-specific health status. METHODS/DESIGN: Patients with a HF diagnosis at four VA Medical Centers were identified through population-based sampling. Patients with a Kansas City Cardiomyopathy Questionnaire (KCCQ, a measure of HF-specific health status) score of < 60 (heavy symptom burden and impaired quality of life) were invited to enroll in the PCDM trial. Enrolled patients were randomized to receive usual care or the PCDM intervention, which included: (1) collaborative care management by VA clinicians including a nurse, cardiologist, internist, and psychiatrist, who worked with patients and their primary care providers to provide guideline-concordant care management, (2) home telemonitoring and guided patient self-management support, and (3) screening and treatment for comorbid depression. The primary study outcome is change in overall KCCQ score. Secondary outcomes include depression, medication adherence, guideline-based care, hospitalizations, and mortality. DISCUSSION: The PCDM trial builds on previous studies of HF disease management by prioritizing patient health status, implementing a collaborative care model of health care delivery, and addressing depression, a key barrier to optimal disease management. The study has been designed as an 'effectiveness trial' to support broader implementation in the healthcare system if it is successful. TRIAL REGISTRATION: Unique identifier: NCT00461513.

On-pump versus off-pump coronary-artery bypass surgery.

BACKGROUND: Coronary-artery bypass grafting (CABG) has traditionally been performed with the use of cardiopulmonary bypass (on-pump CABG). CABG without cardiopulmonary bypass (off-pump CABG) might reduce the number of complications related to the heart-lung machine. METHODS: We randomly assigned 2203 patients scheduled for urgent or elective CABG to either on-pump or off-pump procedures. The primary short-term end point was a composite of death or complications (reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) before discharge or within 30 days after surgery. The primary long-term end point was a composite of death from any cause, a repeat revascularization procedure, or a nonfatal myocardial infarction within 1 year after surgery. Secondary end points included the completeness of revascularization, graft patency at 1 year, neuropsychological outcomes, and the use of major resources. RESULTS: There was no significant difference between off-pump and on-pump CABG in the rate of the 30-day composite outcome (7.0% and 5.6%, respectively; P=0.19). The rate of the 1-year composite outcome was higher for off-pump than for on-pump CABG (9.9% vs. 7.4%, P=0.04). The proportion of patients with fewer grafts completed than originally planned was higher with off-pump CABG than with on-pump CABG (17.8% vs. 11.1%, P<0.001). Follow-up angiograms in 1371 patients who underwent 4093 grafts revealed that the overall rate of graft patency was lower in the off-pump group than in the on-pump group (82.6% vs. 87.8%, P<0.01). There were no treatment-based differences in neuropsychological outcomes or short-term use of major resources. CONCLUSIONS: At 1 year of follow-up, patients in the off-pump group had worse composite outcomes and poorer graft patency than did patients in the on-pump group. No significant differences between the techniques were found in neuropsychological outcomes or use of major resources. (ClinicalTrials.gov number, NCT00032630.).

Costs of Endoscopic vs Open Vein Harvesting for Coronary Artery Bypass Grafting: A Secondary Analysis of the REGROUP Trial.

Importance: Value-based purchasing creates pressure to examine whether newer technologies and care processes, including new surgical techniques, yield any economic advantage. Objective: To compare health care costs and utilization between participants randomized to receive endoscopic vein harvesting (EVH) or open vein harvesting (OVH) during a coronary artery bypass grafting (CABG) procedure. Design, Setting, and Participants: This secondary economic analysis was conducted alongside the 16-site Randomized Endo-Vein Graft Prospective (REGROUP) clinical trial funded by the Department of Veterans Affairs (VA) Cooperative Studies Program. Adults scheduled for urgent or elective bypass involving a vein graft were eligible. The first participant was enrolled in September 2013, with most sites completing enrollment by March 2014. The last participant was enrolled in April 2017. A total of 1150 participants were randomized, with 574 participants receiving OVH and 576 receiving EVH. For this secondary analysis, cost and utilization data were extracted through September 30, 2020. Participants were linked to administrative data in the VA Corporate Data Warehouse and activity-based cost data starting with the index procedure. Interventions: EVH vs OVH, with comparisons based on intention to treat. Main Outcomes and Measures: Discharge costs for the index procedure as well as follow-up costs (including intended and unintended events; mean [SD] follow-up time, 33.0 [19.9] months) were analyzed, with results from different statistical models compared to test for robustness (ie, lack of variation across models). All costs represented care provided or paid by the VA, standardized to 2020 US dollars. Results: Among 1150 participants, the mean (SD) age was 66.4 (6.9) years; most participants (1144 [99.5%] were male. With regard to race and ethnicity, 6 participants (0.5%) self-reported as American Indian or Alaska Native, 10 (0.9%) as Asian or Pacific Islander, 91 (7.9%) as Black, 62 (5.4%) as Hispanic, 974 (84.7%) as non-Hispanic White, and 6 (0.5%) as other race and/or ethnicity; data were missing for 1 participant (0.1%). The unadjusted mean (SD) costs for the index CABG procedure were $76 607 ($43 883) among patients who received EVH and $75 368 ($45 900) among those who received OVH, including facility costs, insurance costs, and physician-related costs (commonly referred to as provider costs in Centers for Medicare and Medicaid and insurance data). No significant differences were found in follow-up costs; per 90-day follow-up period, EVH was associated with a mean (SE) added cost of $302 ($225) per patient. The results were highly robust to the statistical model. Conclusions and Relevance: In this study, EVH was not associated with a reduction in costs for the index CABG procedure or follow-up care. Therefore, the choice to provide EVH may be based on surgeon and patient preferences. Trial Registration: ClinicalTrials.gov Identifier: NCT01850082.

Ten-Year Outcomes of Off-Pump vs On-Pump Coronary Artery Bypass Grafting in the Department of Veterans Affairs: A Randomized Clinical Trial.

IMPORTANCE: The long-term benefits of off-pump ("beating heart") vs on-pump coronary artery bypass grafting (CABG) remain controversial. OBJECTIVE: To evaluate the 10-year outcomes and costs of off-pump vs on-pump CABG in the Department of Veterans Affairs (VA) Randomized On/Off Bypass (ROOBY) trial. DESIGN, SETTING, AND PARTICIPANTS: From February 27, 2002, to May 7, 2007, 2203 veterans in the ROOBY trial were randomly assigned to off-pump or on-pump CABG procedures at 18 participating VA medical centers. Per protocol, the veterans were observed for 10 years; the 10-year, post-CABG clinical outcomes and costs were assessed via centralized abstraction of electronic medical records combined with merges to VA and non-VA databases. With the use of an intention-to-treat approach, analyses were performed from May 7, 2017, to December 9, 2021. INTERVENTIONS: On-pump and off-pump CABG procedures. MAIN OUTCOMES AND MEASURES: The 10-year coprimary end points included all-cause death and a composite end point identifying patients who had died or had undergone subsequent revascularization (ie, percutaneous coronary intervention [PCI] or repeated CABG); these 2 end points were measured dichotomously and as time-to-event variables (ie, time to death and time to composite end points). Secondary 10-year end points included PCIs, repeated CABG procedures, changes in cardiac symptoms, and 2018-adjusted VA estimated costs. Changes from baseline to 10 years in post-CABG, clinically relevant cardiac symptoms were evaluated for New York Heart Association functional class, Canadian Cardiovascular Society angina class, and atrial fibrillation. Outcome differences were adjudicated by an end points committee. Given that pre-CABG risks were balanced, the protocol-driven primary and secondary hypotheses directly compared 10-year treatment-related effects. RESULTS: A total of 1104 patients (1097 men [99.4%]; mean [SD] age, 63.0 [8.5] years) were enrolled in the off-pump group, and 1099 patients (1092 men [99.5%]; mean [SD] age, 62.5 [8.5] years) were enrolled in the on-pump group. The 10-year death rates were 34.2% (n = 378) for the off-pump group and 31.1% (n = 342) for the on-pump group (relative risk, 1.05; 95% CI, 0.99-1.11; P = .12). The median time to composite end point for the off-pump group (4.6 years; IQR, 1.4-7.5 years) was approximately 4.3 months shorter than that for the on-pump group (5.0 years; IQR, 1.8-7.9 years; P = .03). No significant 10-year treatment-related differences were documented for any other primary or secondary end points. After the removal of conversions, sensitivity analyses reconfirmed these findings. CONCLUSIONS AND RELEVANCE: No off-pump CABG advantages were found for 10-year death or revascularization end points; the time to composite end point was lower in the off-pump group than in the on-pump group. For veterans, in the absence of on-pump contraindications, a case cannot be made for supplanting the traditional on-pump CABG technique with an off-pump approach. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01924442.

Tadalafil for veterans with chronic obstructive pulmonary disease-pulmonary hypertension: A multicenter, placebo-controlled randomized trial.

Treating Veterans with chronic obstructive pulmonary disease complicated by pulmonary hypertension (COPD-PH) using phosphodiesterase type-5 inhibitor pharmacotherapy is common, but efficacy data are lacking. To address this further, patients with COPD-PH from five Department of Veterans Affairs hospitals were randomized (1∶1) to receive placebo or oral tadalafil (40 mg/day) for 12 months. The primary endpoint was changed from baseline in 6-min walk distance at 12 months. Secondary endpoints included change from baseline in pulmonary vascular resistance, mean pulmonary artery pressure, and symptom burden by the University of California San Diego shortness of breath questionnaire scale at 6 months. A total of 42 subjects (all male; 68 ± 7.6 years old) were randomized to placebo (N = 14) or tadalafil (N = 28). The group imbalance was related to under-enrollment. Compared to placebo, no significant difference was observed in the tadalafil group for change from the primary endpoint or change in mean pulmonary artery pressure or pulmonary vascular resistance from baseline at 6 months. A clinically meaningful improvement was observed in the secondary endpoint of shortness of breath questionnaire score in the tadalafil versus placebo group at 6 months. There was no significant difference in major adverse events between treatment groups, and tadalafil was well tolerated overall. For Veterans with COPD-PH enrolled in this study, once-daily treatment with tadalafil did not improve 6-min walk distance or cardiopulmonary hemodynamics although a decrease in shortness of breath was observed. Under-enrollment and imbalanced randomization confound interpreting conclusions from this clinical trial and limit the generalization of our findings.

Safety and efficacy of dual-axis rotational coronary angiography vs. standard coronary angiography.

OBJECTIVE: To determine the safety and efficacy of dual-axis rotational coronary angiography (DARCA) by directly comparing it to standard coronary angiography (SA). BACKGROUND: Standard coronary angiography (SA) requires numerous fixed static images of the coronary tree and has multiple well-documented limitations. Dual-axis rotational coronary angiography (DARCA) is a new rotational acquisition technique that entails simultaneous LAO/RAO and cranial/caudal gantry movement. This technological advancement obtains numerous unique images of the left or right coronary tree with a single coronary injection. We sought to assess the safety and efficacy of DARCA as well as determine DARCA's adequacy for CAD screening and assessment. METHODS: Thirty patients underwent SA following by DARCA. Contrast volume, radiation dose (DAP) and procedural time were recorded for each method to assess safety. For DARCA acquisitions, blood pressure (BP), heart rate (HR), symptoms and any arrhythmias were recorded. All angiograms were reviewed for CAD screening adequacy by two independent invasive cardiologists. RESULTS: Compared to SA, use of DARCA was associated with a 51% reduction in contrast, 35% less radiation exposure, and 18% shorter procedural time. Both independent reviewers noted DARCA to be at least equivalent to SA with respect to the ability to screen for CAD. CONCLUSION: DARCA represents a new angiographic technique which is equivalent in terms of image quality and is associated with less contrast use, radiation exposure, and procedural time than SA.

Coronary Artery Bypass Grafting Transit Time Flow Measurement: Graft Patency and Clinical Outcomes.

BACKGROUND: This subanalysis of the Randomized On-Off Bypass (ROOBY) trial examined transit time flow measurement (TTFM) use and its impact on graft patency and long-term clinical outcomes after coronary artery bypass graft surgery. METHODS: Use of TTFM for ROOBY centers and surgeons was assessed. Comparative patient outcomes based on TTFM use included 1-year graft patency and 1-year and 5-year major adverse cardiac events: all-cause mortality, nonfatal myocardial infarction, and revascularization (percutaneous coronary intervention or repeat coronary artery bypass graft surgery). RESULTS: Transit time flow measurement was used in 1067 patients (TTFM group) and not used in 501 patients (non-TTFM group); of the TTFM group, median percentage TTFM use was 79% (interquartile range, 41% to 98%) among 18 Veterans Affairs Medical Centers, and 74% (interquartile range, 13% to 98%) among 48 surgeons. Patients were comparable in age (63 ± 8.5 years TTFM vs 62 ± 8 years non-TTFM, P = .30) and estimated 30-day mortality risk (1.8 ± 1.7 TTFM vs 1.9 non-TTFM, P = .53). One-year FitzGibbon A patency was 83% (1600 of 1988 grafts) for TTFM assessed grafts and 78% (629 of 803) for non-TTFM assessed grafts (P < .01). Fewer TTFM patients had an occluded graft (29%, vs 38% non-TTFM; P = .01). Comparing TTFM patients with non-TTFM patients, 5-year major adverse cardiac event rates were 30% vs 25% (P = .06). Individual component rates were 14% vs 11% for death (P = .06), 12% vs 8.8% for myocardial infarction (P = .07), and 13% vs 12% for revascularization (P = .62). CONCLUSIONS: The association of TTFM use with graft patency and clinical outcome is uncertain. Future randomized studies that account for patient risk factors and practice variation would help address this knowledge gap.

New-onset postoperative atrial fibrillation impact on 5-year clinical outcomes and costs.

OBJECTIVE: The impact of new-onset postoperative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG) surgery on long-term clinical outcomes and costs is not known. This subanalysis of the Veterans Affairs "Randomized On/Off Bypass Follow-up Study" compared 5-year outcomes and costs between patients with and without POAF. METHODS: Of the 2203 veterans in the study, 100 with pre-CABG atrial fibrillation (93) or missing data (7) were excluded (4.8%). Unadjusted and risk-adjusted outcomes were compared between new-onset POAF (n = 551) and patients without POAF (n = 1552). Five-year clinical outcomes included mortality, major adverse cardiovascular events (MACE, comprising mortality, repeat revascularization, and myocardial infarction), MACE subcomponents, stroke, and costs. A stringent P value of ≤.01 was required to identify statistical significance. RESULTS: Patients with POAF were older and had more complex comorbidities. Unadjusted 5-year all-cause mortality was 16.3% POAF versus 11.9% no-POAF, P = .008. Unadjusted cardiac-mortality was 7.4% versus 4.8%, P = .022. There were no differences between groups in any other unadjusted outcomes including MACE or stroke. After risk adjustment, there were no significant differences between groups in 5-year all-cause mortality (POAF odds ratio, 1.19; 99% confidence interval, 0.81-1.75) or cardiac mortality (odds ratio, 1.51, 99% confidence interval, 0.88-2.60). Adjusted first-year post-CABG costs were $15,300 greater for patients with POAF, but 2- through 5-year costs were similar. CONCLUSIONS: No 5-year risk-adjusted outcome differences were found between patients with and without POAF after CABG. Although first-year costs were greater in patients with POAF, this difference did not persist in subsequent years.

DITPA (3,5-Diiodothyropropionic Acid), a thyroid hormone analog to treat heart failure: phase II trial veterans affairs cooperative study.

BACKGROUND: In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. METHODS AND RESULTS: This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n=57 to DITPA, n=29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure-specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (-20%), low-density lipoprotein cholesterol (-30%), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. CONCLUSIONS: DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.

Incidence and Prognostic Impact of Incomplete Revascularization Documented by Coronary Angiography 1 Year After Coronary Artery Bypass Grafting.

Complete revascularization (CR) at the time of coronary artery bypass graft (CABG) surgery improves long-term cardiac outcomes. No studies have previously reported angiographically confirmed CR rates post-CABG. This study's aim was to assess the impact upon long-term outcomes of CR versus incomplete revascularization (IR), confirmed by coronary angiography 1 year after CABG. Randomized On/Off Bypass Study patients who returned for protocol-specified 1-year post-CABG coronary angiograms were included. Patients with a widely patent graft supplying the major diseased artery within each diseased coronary territory were considered to have CR. Outcomes were all-cause mortality and major adverse cardiovascular events (MACE; all-cause mortality, nonfatal myocardial infarction, repeat revascularization) over the 4 years after angiography. Of the 1,276 patients, 756 (59%) had CR and 520 (41%) had IR. MACE was 13% CR versus 26% IR, p <0.001. This difference was driven by fewer repeat revascularizations (5% CR vs 18% IR; p <0.001). There were no differences in mortality (7.1% CR vs 8.1% IR, p = 0.13) or myocardial infarction (4% in both). Adjusted multivariable models confirmed CR was associated with reduced MACE (odds ratio 0.44, 95% confidence interval 0.33 to 0.58, p <0.01), but had no impact on mortality. In conclusion, CR confirmed by post-CABG angiography was associated with improved MACE but not mortality. Repeat revascularization of patients with IR, driven by knowledge of the research angiography results, may have ameliorated potential mortality differences.