Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF. OBJECTIVES: This study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery. METHODS: This phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65, ≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF ≥30 seconds. RESULTS: Among 312 modified intention-to-treat participants (placebo, n = 102; 125 U, n = 104; and 250 U, n = 106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG + valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95% CI: 0.58-1.10; P = 0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95% CI: 0.79-1.37; P = 0.78). The primary endpoint was reduced in the 125-U group in those ≥65 years (RR: 0.64; 95% CI: 0.43-0.94; P = 0.02) with a greater reduction in CABG-only participants ≥65 years (RR: 0.49; 95% CI: 0.27-0.87; P = 0.01). Rehospitalization and rates of adverse events were similar across the 3 groups. CONCLUSIONS: There were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants ≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68).

Consensus statement-graft treatment in cardiovascular bypass graft surgery.

Coronary artery bypass grafting (CABG) is and continues to be the preferred revascularization strategy in patients with multivessel disease. Graft selection has been shown to influence the outcomes following CABG. During the last almost 60 years saphenous vein grafts (SVG) together with the internal mammary artery have become the standard of care for patients undergoing CABG surgery. While there is little doubt about the benefits, the patency rates are constantly under debate. Despite its acknowledged limitations in terms of long-term patency due to intimal hyperplasia, the saphenous vein is still the most often used graft. Although reendothelialization occurs early postoperatively, the process of intimal hyperplasia remains irreversible. This is due in part to the persistence of high shear forces, the chronic localized inflammatory response, and the partial dysfunctionality of the regenerated endothelium. "No-Touch" harvesting techniques, specific storage solutions, pressure controlled graft flushing and external stenting are important and established methods aiming to overcome the process of intimal hyperplasia at different time levels. Still despite the known evidence these methods are not standard everywhere. The use of arterial grafts is another strategy to address the inferior SVG patency rates and to perform CABG with total arterial revascularization. Composite grafting, pharmacological agents as well as latest minimal invasive techniques aim in the same direction. To give guide and set standards all graft related topics for CABG are presented in this expert opinion document on graft treatment.

Outcomes after surgical revascularization in diabetic patients.

OBJECTIVES: Patients with diabetes mellitus (DM) undergoing coronary artery bypass grafting (CABG) have been repeatedly demonstrated to have worse clinical outcomes compared to patients without DM. The objective of this study was to evaluate the impact of DM on 1-year clinical outcomes after isolated CABG. METHODS: The European DuraGraft registry included 1130 patients (44.6%) with and 1402 (55.4%) patients without DM undergoing isolated CABG. Intra-operatively, all free venous and arterial grafts were treated with an endothelial damage inhibitor. Primary end point in this analysis was the incidence of a major adverse cardiac event (MACE), a composite of all-cause death, repeat revascularization or myocardial infarction at 1 year post-CABG. To balance between differences in baseline characteristics (n = 1072 patients in each group), propensity score matching was used. Multivariable Cox proportional hazards regression was performed to identify independent predictors of MACE. RESULTS: Diabetic patients had a higher cardiovascular risk profile and EuroSCORE II with overall more comorbidities. Patients were comparable in regard to surgical techniques and completeness of revascularization. At 1 year, diabetics had a higher MACE rate {7.9% vs 5.5%, hazard ratio (HR) 1.43 [95% confidence interval (CI) 1.05-1.95], P = 0.02}, driven by increased rates of death [5.6% vs 3.5%, HR 1.61 (95% CI 1.10-2.36), P = 0.01] and myocardial infarction [2.8% vs 1.4%, HR 1.99 (95% CI 1.12-3.53) P = 0.02]. Following propensity matching, no statistically significant difference was found for MACE [7.1% vs 5.7%, HR 1.23 (95% CI 0.87-1.74) P = 0.23] or its components. Age, critical operative state, extracardiac arteriopathy, ejection fraction ≤50% and left main disease but not DM were identified as independent predictors for MACE. CONCLUSIONS: In this study, 1-year outcomes in diabetics undergoing isolated CABG were comparable to patients without DM.

Clinical outcomes and quality of life after contemporary isolated coronary bypass grafting: a prospective cohort study.

OBJECTIVES: The objective of the European Multicenter Registry to Assess Outcomes in coronary artery bypass grafting (CABG) patients (DuraGraft Registry) was to determine clinical outcomes and quality of life (QoL) after contemporary CABG that included isolated CABG and combined CABG/valve procedures, using an endothelial damage inhibitor (DuraGraft) intraoperatively for conduit preservation. Here, we report outcomes in the patient cohort undergoing isolated CABG. METHODS: The primary outcome was the composite of all-cause death, myocardial infarction (MI), or repeat revascularization (RR) [major adverse cardiac events (MACE)] at 1 year. Secondary outcomes included the composite of all-cause death, MI, RR, or stroke [major adverse cardiac and cerebrovascular events (MACCE)], and QoL. QoL was assessed with the EuroQol-5 Dimension questionnaire. Independent risk factors for MACE at 1 year were determined using Cox regression analysis. RESULTS: A total of 2532 patients (mean age, 67.4±9.2 years; 82.5% male) underwent isolated CABG. The median EuroScore II was 1.4 [interquartile range (IQR), 0.9-2.3]. MACE and MACCE rates at 1 year were 6.6% and 7.8%, respectively. The rates of all-cause death, MI, RR, and stroke were 4.4, 2.0, 2.2, and 1.9%, respectively. The 30-day mortality rate was 2.3%. Age, extracardiac arteriopathy, left ventricular ejection fraction less than 50%, critical operative state, and left main disease were independent risk factors for MACE. QoL index values improved from 0.84 [IQR, 0.72-0.92] at baseline to 0.92 [IQR, 0.82-1.00] at 1 year ( P <0.0001). CONCLUSION: Contemporary European patients undergoing isolated CABG have a low 1-year clinical event rate and an improved QoL.

Coronary endarterectomy in patients with diffuse coronary artery disease: assessment of graft patency with computed tomography angiography.

BACKGROUND: With a growing population of patients with advanced coronary artery disease (CAD), many of whom have undergone prior percutaneous coronary interventions, coronary endarterectomy (CE) allows for the extension of revascularization in patients with otherwise limited options. Whether adjunctive CE associated with standard surgery, combined with contemporary antiplatelet therapy, improves outcomes remains largely unknown. METHODS: We studied 147 consecutive patients who underwent 154 adjunctive CE procedures for advanced CAD between January 2015 and January 2018. We used computed tomography angiography (CTA) in a subgroup of 32 consecutive patients who underwent CE during coronary artery bypass grafting after June 2016 to assess graft and coronary patency. RESULTS: Patients (mean age 67 ± SD 10 yr) underwent CE of the right (102 patients), the left anterior descending (LAD, 22 patients) and the circumflex (17 patients) coronary arteries. Seven patients (5%) experienced a procedural myocardial infarction and there were no perioperative deaths. Among the 32 patients who underwent CTA 3 months after surgery, the mean patency of the endarterectomized coronary arteries and bypass grafts was 90% and 88%, respectively. All 6 arterial grafts on the LAD artery were patent. The mean survival rate and the mean rate of freedom from major adverse cardiovascular events was 95% ± 2% and 95% ± 6%, respectively. The patency rate was 100 % for patients evaluated at 3-year follow up. CONCLUSION: Coronary endarterectomy offers a surgical option for patients with diffuse CAD who may be unsuitable for coronary bypass alone. Grafts and endarterectomized coronary artery patency remain adequate and explain the excellent patient survival and the freedom rate from major adverse cardiovascular events.

Clinical event rate in patients with and without left main disease undergoing isolated coronary artery bypass grafting: results from the European DuraGraft Registry.

OBJECTIVES: Left main coronary artery disease (LMCAD) is considered an independent risk factor for clinical events after coronary artery bypass grafting (CABG). We have conducted a subgroup analysis of the multicentre European DuraGraft Registry to investigate clinical event rates at 1 year in patients with and without LMCAD undergoing isolated CABG in contemporary practice. METHODS: Patients undergoing isolated CABG were selected. The primary end point was the incidence of a major adverse cardiac event (MACE) defined as the composite of death, myocardial infarction (MI) or repeat revascularization (RR) at 1 year. The secondary end point was major adverse cardiac and cerebrovascular events (MACCE) defined as MACE plus stroke. Propensity score matching was performed to balance for differences in baseline characteristics. RESULTS: LMCAD was present in 1033 (41.2%) and absent in 1477 (58.8%) patients. At 1 year, the MACE rate was higher for LMCAD patients (8.2% vs 5.1%, P = 0.002) driven by higher rates of death (5.4% vs 3.4%, P = 0.016), MI (3.0% vs 1.3%, P = 0.002) and numerically higher rates of RR (2.8% vs 1.8%, P = 0.13). The incidence of MACCE was 8.8% vs 6.6%, P = 0.043, with a stroke rate of 1.0% and 2.4%, P = 0.011, for the LMCAD and non-LMCAD groups, respectively. After propensity score matching, the MACE rate was 8.0% vs 5.2%, P = 0.015. The incidence of death was 5.1% vs 3.7%, P = 0.10, MI 3.0% vs 1.4%, P = 0.020, and RR was 2.7% vs 1.6%, P = 0.090, for the LMCAD and non-LMCAD groups, respectively. Less strokes occurred in LMCAD patients (1.0% vs 2.4%, P = 0.017). The MACCE rate was not different, 8.5% vs 6.7%, P = 0.12. CONCLUSIONS: In this large registry, LMCAD was demonstrated to be an independent risk factor for MACE after isolated CABG. Conversely, the risk of stroke was lower in LMCAD patients. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02922088.

The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study.

BACKGROUND: Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations. METHODS: The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. CONCLUSIONS: The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Use of Mobile-Based Application for Collection of Patient-Reported Outcomes in Cardiac Surgery.

OBJECTIVE: Application-based (app) technology has been studied for patient engagement and collecting patient-reported outcomes (PROs) in several surgical specialties with limited research in cardiac surgery. The aim of study was to determine the effectiveness of app-based technology for collecting PROs, improving the patient experience, and reducing health services utilization in a cardiac surgery center. METHODS: Patients accessed an interactive app via smartphones. Patients were guided from 4 weeks preoperative to 4 weeks postoperative via reminders, tasks, PRO surveys, and evidence-based education. In the postoperative period, patients were engaged with daily health surveys to track warning signs and recovery milestones. Based on the patient's signs and symptoms, the app escalated lower risk issues to self-care education or higher risk issues to the care team (e.g., phone call to a nurse). RESULTS: Sixty-six percent of patients (730 of 1,108) activated their app account. Two hundred seventy-seven patients completed an end-of-program feedback survey, with 94% of patients recommending the app and 98% of patients finding the app was helpful in recovery. Patients also reported using the app to avoid unnecessary health services utilization, with 45% of patients using the app to avoid at least 1 phone call and 28% of patients using the app to avoid at least 1 hospital visit. CONCLUSIONS: App-based technology for patient engagement is an effective modality to enhance the patient experience, better understand the trajectory of recovery, and reduce unnecessary health services utilization in cardiac surgery.

Cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons' perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

Active clearance vs conventional management of chest tubes after cardiac surgery: a randomized controlled study.

BACKGROUND: Chest tubes are routinely used after cardiac surgery to evacuate shed mediastinal blood. Incomplete chest drainage due to chest tube clogging can lead to retained blood after cardiac surgery. This can include cardiac tamponade, hemothorax, bloody effusions and postoperative atrial fibrillation (POAF). Prior published non randomized studies have demonstrated that active tube clearance (ATC) of chest tubes can reduce retained blood complications prompting the ERAS Cardiac Society guidelines to recommend this modality. OBJECTIVE: A randomized prospective trial to evaluate whether an ATC protocol aimed at improving chest tube patency without breaking the sterile field could efficiently reduce complications related to retained blood after cardiac surgery. METHODS: This was a pragmatic, single-blinded, parallel randomized control trial held from November 2015 to June 2017 including a 30-day post index surgery follow-up. The setting was two academic centers affiliated with the Université de Montréal School of Medicine; the Montreal Heart Institute and the Hôpital du Sacré-Coeur de Montréal. Adult patients admitted for non-emergent coronary bypass grafting and/or valvular heart surgery through median sternotomy, in sinus rhythm for a minimum of 30 days prior to the surgical intervention were eligible for inclusion. In the active tube clearance group (ATC), a 28F PleuraFlow device was positioned within the mediastinum. In the standard drainage group, a conventional chest tube (Teleflex Inc.) was used. Other chest tubes were left at the discretion of the operating surgeon. RESULTS: A total of 520 adult patients undergoing cardiac surgery were randomized to receive either ATC (n = 257) or standard drainage (n = 263). ATC was associated with a 72% reduction in re-exploration for bleeding (5.7% vs 1.6%, p = .01) and an 89% reduction in complete chest tube occlusion (2% vs 19%, p = .01). There was an 18% reduction in POAF between the ATC and control group that was not statistically significant (31% vs 38%, p = .08). CONCLUSIONS AND RELEVANCE: In this RCT, the implementation of active clearance of chest tubes reduced re-exploration and chest tube clogging in patients after cardiac surgery further supporting recommendations to consider this modality postoperatively. TRIAL REGISTRATION: Clinical Trials NCT02808897 . Retrospectively registered 22 June 2016.

Sudden Tamponade From Vein Graft Side Branch Avulsion on Removal of Temporary Pacemaker Wires.

Temporary epicardial pacing wires are universally used in cardiac surgery and are associated with very low morbidity and mortality. Although rare, serious complications can occur with pacing wires. We present a case of avulsion of a saphenous vein graft side branch caused by removal of pacing wires and leading to pericardial tamponade. Our case favors the use of silk ties rather than hemoclips for occlusion of saphenous vein side branches and illustrates the importance of the location of pacing wires relative to the grafts at the time of coronary artery bypass surgery.

Sequential multidetector computed tomography assessments after venous graft treatment solution in coronary artery bypass grafting.

OBJECTIVES: To assess the effect of DuraGraft (Somahlution Inc, Jupiter, Fla), an intraoperative graft treatment, on saphenous vein grafts in patients undergoing isolated coronary artery bypass grafting. METHODS: Within patients, 2 saphenous vein grafts were randomized to DuraGraft or heparinized saline. Multidetector computed tomography angiography at 1, 3, and 12 months assessed change in wall thickness (primary end point at 3 months), lumen diameter, and maximum narrowing for the whole graft and the proximal 5-cm segment. Safety end points included graft occlusion, death, myocardial infarction, and repeat revascularization. RESULTS: At 3 months, no significant changes were observed between DuraGraft- and saline-treated grafts (125 each) for wall thickness, lumen diameter, and maximum narrowing. At 12 months, DuraGraft-treated grafts demonstrated smaller mean wall thickness, overall (0.12 ± 0.06 vs 0.20 ± 0.31 mm; P = .02) and in the proximal segment (0.11 ± 0.03 vs 0.21 ± 0.33 mm; P = .01). Changes in wall thickness were greater in the proximal segment of saline-treated grafts (0.09 ± 0.29 vs 0.00 ± 0.03 mm; P = .04). Increase in maximum graft narrowing was larger in the proximal segment in the saline-treated grafts (4.7% ± 12.7% vs 0.2% ± 3.8%; P = .01). Nine DuraGraft and 11 saline grafts had occluded or thrombosed. One myocardial infarction was associated with a saline graft occlusion. No deaths or revascularizations were observed. CONCLUSIONS: DuraGraft demonstrated a favorable effect on wall thickness at 12 months, particularly in the proximal segment. Longer-term follow-up in larger studies is needed to evaluate the effect on clinical outcomes.