Outcomes of coronary artery bypass grafting in patients with human immunodeficiency virus infection.

BACKGROUND: With early and effective antiretroviral therapy and improved survival for persons living with human immunodeficiency virus infection (PLHIV), this patient population now faces an increasingly elevated risk of cardiovascular disease. However, the data on outcomes after coronary artery bypass grafting (CABG) for revascularization of coronary artery disease (CAD) in HIV+ patients is limited. METHODS: We conducted a retrospective analysis of 16 patients undergoing isolated CABG at the Medical University of Vienna from 2005 to 2018, who were HIV+ on admission. The primary endpoint of the study was survival. Secondary endpoints included the components of major adverse cardiac and cerebrovascular events (MACCE): cardiovascular death, stroke, myocardial infarction (MI), and repeat revascularization. RESULTS: Patients were followed for a median of 49 months (range, 7-142 months). Survival was 100% and 90% at 1 and 3 years after CABG, respectively. There were no strokes. MI and subsequent repeat revascularization were observed in two patients. CONCLUSION: CABG provides excellent short- and midterm survival and freedom from MACCE in HIV+ patients with CAD requiring revascularization.

Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial.

AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.

Gender Disparities in Cardiac Surgery Trials: Leadership, Authorship, and Patient Enrollment.

BACKGROUND: Studies have highlighted the paucity of women-led randomized controlled trials (RCTs) in cardiovascular medicine. Whether this finding also applies to cardiac surgery has not been evaluated. In this study, we evaluate women authorship, leadership, and women enrollment in cardiac surgery RCTs. METHODS: A systematic literature search was conducted to identify RCTs comparing 2 or more adult cardiac surgical procedures published from 2000 to 2022. Women-led RCTs were defined as those with a woman as either a first or last author. Linear regression and correlation analyses were used. RESULTS: Of 58 RCTs, 8 (13.8%) were women-led; 17 (29.3%) RCTs had no women authors. Overall, 17.9% of all authors were women, but only 1.2% of all authors were women cardiac surgeons and only 19% of the RCTs had a women cardiac surgeon among the authors. The median proportion of women authors was 14.3% by RCT, which was significantly higher in women-led compared with men-led RCTs (28.6% vs 11.8%; P = .01). No significant change in the proportion of women authors was observed during the study period. North American RCTs had a higher proportion of women authors compared with other geographic regions (28.6% vs 12.5%; P = .01). No correlation was found between the proportion of women authors and the proportion of women participants enrolled in individual RCTs. CONCLUSIONS: During the last 2 decades, only a minority of cardiac surgery RCTs were women-led, and no significant increase in women authorship occurred. There are important geographic differences in women authorship.

Ticagrelor or Aspirin After Coronary Artery Bypass in Patients With Chronic Kidney Disease.

BACKGROUND: The optimal antiplatelet therapy for patients with chronic kidney disease (CKD) undergoing coronary artery bypass graft surgery remains unknown. METHODS: This post hoc analysis of the Ticagrelor in Coronary Artery Bypass (TiCAB) trial examined the efficacy and safety of ticagrelor vs aspirin in patients with and patients without CKD. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), namely, the composite of cardiovascular death, stroke, myocardial infarction, or revascularization at 1 year after coronary artery bypass graft surgery. Secondary endpoints included individual components of the primary endpoint, all-cause death, and major bleeding. RESULTS: Chronic kidney disease was present in 276 of 1843 randomized patients (15%). Patients with CKD vs patients without CKD had higher 1-year rates of MACCE (13% vs 8.3%, hazard ratio [HR] 1.63; 95% confidence interval [CI], 1.12 to 2.39; P = .01) and major bleeding (5.6% vs 3.1%, HR 1.84; 95% CI, 1.03 to 3.28; P = .04). The 1-year rate of MACCE was increased with ticagrelor vs aspirin in patients with CKD (18.2% vs 8.9%, HR 2.15; 95% CI, 1.08 to 4.30; P = .03), but not in patients without CKD (8.5% vs 8.1%, HR 1.05; 95% CI, 0.74 to 1.49; P = .79; Pinteraction = .067). There was no difference in the 1-year rate of major bleeding with ticagrelor vs aspirin in patients with CKD (6.6% vs 4.7%, HR 1.44; 95% CI, 0.52 to 3.97; P = .48) and patients without CKD (3.3% vs 2.9%, HR 1.14; 95% CI, 0.64 to 2.01; P = .65). CONCLUSIONS: Among patients with CKD and coronary artery bypass graft surgery, those who received ticagrelor had a higher incidence of MACCE but a similar incidence of major bleeding compared with those who received aspirin.

Effects of the harvesting technique and external stenting on progression of vein graft disease 2 years after coronary artery bypass.

OBJECTIVES: In a post hoc analysis of the VEST III trial, we investigated the effect of the harvesting technique on saphenous vein graft (SVG) patency and disease progression after coronary artery bypass grafting. METHODS: Angiographic outcomes were assessed in 183 patients undergoing open (126 patients, 252 SVG) or endoscopic harvesting (57 patients, 114 SVG). Overall SVG patency was assessed by computed tomography angiography at 6 months and by coronary angiography at 2 years. Fitzgibbon patency (FP I, II and III) and intimal hyperplasia (IH) in a patient subset were assessed by coronary angiography and intravascular ultrasound, respectively, at 2 years. RESULTS: Baseline characteristics were similar between patients who underwent open and those who underwent endoscopic harvesting. Open compared with endoscopic harvesting was associated with higher overall SVG patency rates at 6 months (92.9% vs 80.4%, P = 0.04) and 2 years (90.8% vs 73.9%, P = 0.01), improved FP I, II and III rates (65.2% vs 49.2%; 25.3% vs 45.9%, and 9.5% vs 4.9%, respectively; odds ratio 2.81, P = 0.09) and reduced IH area (-31.8%; P = 0.04) and thickness (-28.9%; P = 0.04). External stenting was associated with improved FP I, II and III rates (odds ratio 2.84, P = 0.01), reduced IH area (-19.5%; P < 0.001) and thickness (-25.0%; P < 0.001) in the open-harvest group and reduced IH area (-12.7%; P = 0.01) and thickness (-9.5%; P = 0.21) in the endoscopic-harvest group. CONCLUSIONS: A post-hoc analysis of the VEST III trial showed that open harvesting is associated with improved overall SVG patency and reduced IH. External stenting reduces SVG disease progression, particularly with open harvesting.

Prognostic impact of secondary prevention after coronary artery bypass grafting-insights from the TiCAB trial.

OBJECTIVES: There are disparities in the adherence to guideline-recommended therapies after coronary artery bypass graft (CABG). We therefore sought to evaluate the effect of guideline-adherent medical secondary prevention on 1-year outcome after CABG. METHODS: Data were taken from the randomized 'Ticagrelor in CABG' trial. From April 2013 until April 2017, patients who underwent CABG were included. For the present analysis, we compared patients who were treated with optimal medical secondary prevention with those where 1 or more of the recommended medications were missing. RESULTS: Follow-up data at 12 months were available in 1807 patients. About half (54%) of them were treated with optimal secondary prevention. All-cause mortality [0.5% vs 3.5%, hazard ratio (HR) 0.14 (0.05-0.37), P < 0.01], cardiovascular mortality [0.1% vs 1.7%, HR 0.06 (0.01-0.46), P = 0.007] and major adverse events [6.5% vs 11.5%, HR 0.54 (0.39-0.74), P < 0.01] were significantly lower in the group with optimal secondary prevention. The multivariable model for the primary end point based on binary concordance to guideline recommended therapy identified 3 independent factors: adherence to guideline recommended therapy [HR 0.55 (0.39-0.78), P < 0.001]; normal renal function [HR 0.99 (0.98-0.99), P = 0.040]; and off-pump surgery [HR 2.06 (1.02-4.18), P = 0.045]. CONCLUSIONS: Only every second patient receives optimal secondary prevention after CABG. Guideline adherent secondary prevention therapy is associated with lower mid-term mortality and less adverse cardiovascular events after 12 months.

A Novel Endothelial Damage Inhibitor Reduces Oxidative Stress and Improves Cellular Integrity in Radial Artery Grafts for Coronary Artery Bypass.

The radial artery (RA) is a frequently used conduit in coronary artery bypass grafting (CABG). Endothelial injury incurred during graft harvesting promotes oxidative damage, which leads to graft disease and graft failure. We evaluated the protective effect of DuraGraft®, an endothelial damage inhibitor (EDI), on RA grafts. We further compared the protective effect of the EDI between RA grafts and saphenous vein grafts (SVG). Samples of RA (n = 10) and SVG (n = 13) from 23 patients undergoing CABG were flushed and preserved with either EDI or heparinized Ringer's lactate solution (RL). The effect of EDI vs. RL on endothelial damage was evaluated ex vivo and in vitro using histological analysis, immunofluorescence staining, Western blot, and scanning electron microscopy. EDI-treated RA grafts showed a significant reduction of endothelial and sub-endothelial damage. Lower level of reactive oxygen species (ROS) after EDI treatment was correlated with a reduction of hypoxic damage (eNOS and Caveolin-1) and significant increase of oxidation-reduction potential. Additionally, an increased expression of TGFß, PDGFα/ß, and HO-1 which are indicative for vascular protective function were observed after EDI exposure. EDI treatment preserves functionality and integrity of endothelial and intimal cells. Therefore, EDI may have the potential to reduce the occurrence of graft disease and failure in RA grafts in patients undergoing CABG.

Endothelial damage inhibitors for improvement of saphenous vein graft patency in coronary artery bypass grafting.

The saphenous vein graft (SVG) remains the most commonly used conduit in coronary artery bypass grafting (CABG). In light of this further research must be aimed at the development of strategies to optimize SVG patency and thereby improve both short- and long-term outcomes of CABG surgery. SVG patency in large part depends on the protection of the structural and functional integrity of the vascular endothelium at the time of conduit harvesting, including optimal storage conditions to prevent endothelial damage. This review provides an overview of currently available storage and preservation solutions, including novel endothelial damage inhibitors, and their role in mitigating endothelial damage and vein graft failure.

Routine preoperative aortic computed tomography angiography is associated with reduced risk of stroke in coronary artery bypass grafting: a propensity-matched analysis.

OBJECTIVES: The aim of this study was to determine stroke rates in patients who did or did not undergo routine computed tomography angiography (CTA) aortic imaging before isolated coronary artery bypass grafting (CABG). METHODS: We conducted a retrospective analysis of a prospectively maintained single-centre registry. Between 2009 and 2016, a total of 2320 consecutive patients who underwent isolated CABG at our institution were identified. Propensity score matching was used to create a paired cohort of patients with similar baseline characteristics who did (CTA cohort) or did not (non-CTA cohort) undergo preoperative aortic CTA. The primary end point of the analysis was in-hospital stroke. RESULTS: In 435 propensity score-matched pairs, stroke occurred in 4 patients (0.92%) in the CTA cohort and in 14 patients (3.22%) in the non-CTA cohort (P = 0.017). Routine preoperative aortic CTA was associated with a significantly reduced risk of in-hospital stroke [relative risk 0.29, 95% confidence interval (CI) 0.09-0.86; P = 0.026; absolute risk reduction 2.3%, 95% CI 0.4-4.2; P = 0.017; number needed to treat = 44, 95% CI 24-242]. CONCLUSIONS: A preoperative screening for atheromatous aortic disease using CTA is associated with reduced risk of stroke after CABG. The routine use of preoperative aortic CTA could be applied so that surgical manipulation of the ascending aorta can be selectively reduced or avoided in patients with atheromatous aortic disease.

Coronary artery bypass grafting and perioperative stroke: imaging of atherosclerotic plaques in the ascending aorta with ungated high-pitch CT-angiography.

Perioperative stroke is a devastating complication after coronary artery bypass graft (CABG) surgery, with atherosclerosis of the ascending aorta as important risk factor. During surgical manipulation, detachment of plaques can lead to consecutive embolization into brain-supplying arteries. High-pitch computed tomography angiography (HP-CTA) represents a non-invasive imaging modality, which provides the opportunity for comprehensive imaging of the ascending aorta, including plaque detection and advanced characterization. In our present retrospective study on 719 individuals, who had undergone HP-CTA within 6 months prior to CABG, atherosclerotic disease of the ascending aorta was evaluated with respect to perioperative stroke rates. For image analysis, the ascending aorta was divided into a proximal and distal part, consisting of four segments, and evaluated for presence and distribution of calcified and mixed plaques. All patients with perioperative stroke presented with atherosclerotic disease of the ascending aorta. The stroke rate was significantly associated with the presence and extent of atherosclerotic disease. Patients burdened with mixed plaques presented with significantly higher perioperative stroke rates. This study demonstrates that HP-CTA allows accurate evaluation of plaque extent and composition in the ascending aorta, and therefore may improve risk stratification of stroke prior to CABG.

Ticagrelor monotherapy versus aspirin in patients undergoing multiple arterial or single arterial coronary artery bypass grafting: insights from the TiCAB trial.

OBJECTIVES: We evaluated the effect of ticagrelor monotherapy on outcomes after multiple arterial grafting (MAG) or single arterial grafting (SAG) in coronary artery bypass grafting (CABG). METHODS: In a post hoc, non-randomized analysis of the TiCAB (Ticagrelor in CABG; ClinicalTrials.gov NCT01755520) trial, we compared event rates for ticagrelor versus aspirin in patients undergoing MAG and SAG. Primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction (MI), stroke or repeat revascularization 1 year after CABG. Secondary outcomes included individual components of the primary end point, all-cause death and bleeding. RESULTS: Among 1753 patients, 998 patients underwent MAG and 755 patients underwent SAG. There was no significant difference in the 1-year primary composite outcome for ticagrelor versus aspirin with MAG [7.2% vs 7.9%; hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.57-1.43; P = 0.66] or SAG (12.3% vs 8.6%; HR 1.47, 95% CI 0.93-2.31; P = 0.10). Event rates for cardiovascular death, MI, stroke, repeat revascularization and all-cause death were similar for both treatment groups with MAG and SAG. No significant difference in major bleeding was observed for ticagrelor versus aspirin with MAG (2.6% vs 2.7%; HR 0.95, 95% CI 0.44-2.05; P = 0.90) or SAG (5.8% vs 4.0%; HR 1.49, 95% CI 0.77-2.89; P = 0.24). CONCLUSIONS: In patients undergoing either MAG or SAG in the TiCAB trial, ticagrelor monotherapy compared with aspirin did not affect the rate of cardiovascular death, non-fatal MI, stroke or repeat revascularization, or the rate of bleeding, at 1 year after CABG.

Low molecular weight heparin as an alternative to unfractionated heparin in the immediate postoperative period after left ventricular assist device implantation.

We present a regimen for anticoagulation in the immediate postoperative period after left ventricular assist device (LVAD) implantation using low molecular weight heparin (LMWH) as an alternative to unfractionated heparin. Between May and September 2007, eight consecutive patients undergoing LVAD implantation for advanced heart failure received the LMWH nadroparin. Nadroparin was given twice daily to achieve anti-Factor Xa activity target peak levels of 0.4 +/- 0.1 U/mL. The antiplatelet therapy consisted of aspirin (100 mg/day) and dipyridamole (3 x 75 mg/day). One patient underwent heart transplantation, three patients died, and four patients continued to receive device support. The median duration of support was 78 days (range, 46 to 174). No major bleeding was observed; minor bleeding occurred in three patients. In two patients, pump thrombosis was suspected. There were two ischemic and no hemorrhagic strokes. The use of LMWH may provide a new anticoagulation treatment option in the immediate postoperative period after LVAD implantation.

The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity.

Inducible costimulatory molecule (ICOS) plays a pivotal role in T cell activation and Th1/Th2 differentiation. ICOS blockade has disparate effects on immune responses depending on the timing of blockade. Its role in transplantation immunity, however, remains incompletely defined. We used a vascularized mouse cardiac allograft model to explore the role of ICOS signaling at different time points after transplantation, targeting immune initiation (early blockade) or the immune effector phase (delayed blockade). In major histocompatibility-mismatched recipients, ICOS blockade prolonged allograft survival using both protocols but did so more effectively in the delayed-treatment group. By contrast, in minor histocompatibility-mismatched recipients, early blockade accelerated rejection and delayed blockade prolonged graft survival. Alloreactive CD4+ T cell expansion and alloantibody production were suppressed in both treatment groups, whereas only delayed blockade resulted in suppression of effector CD8+ T cell generation. After delayed ICOS blockade, there was a diminished frequency of allospecific IL-10-producing cells and an increased frequency of both IFN-gamma- and IL-4-producing cells. The beneficial effects of ICOS blockade in regulating allograft rejection were seen in the absence of CD28 costimulation but required CD8+ cells, cytotoxic T lymphocyte antigen-4, and an intact signal transducer and activator of transcription-6 pathway. These data define the complex functions of the ICOS-B7h pathway in regulating alloimmune responses in vivo.

Low-molecular-weight heparin for anti-coagulation after left ventricular assist device implantation.

BACKGROUND: Anti-coagulation is required in patients with left ventricular assist devices (LVADs). We evaluated the feasibility of low-molecular-weight heparin (LMWH) for initiation of anti-coagulation and transitioning to oral anti-coagulation after LVAD implantation. METHODS: This single-center study included 78 consecutive patients who underwent either Thoratec HeartMate II LVAD (n = 27) or HeartWare ventricular assist device (HVAD, n = 51) implantation. The LMWHs enoxaparin (n = 50) and dalteparin (n = 28) were used. LMWH was started within 24 hours post-operatively in 79.5% of patients. No anti-coagulation was given before starting LMWH therapy. LMWH activity was monitored by determination of anti-factor Xa levels in plasma. RESULTS: The majority of patients (80.7%) had peak anti-Xa activity within the defined range of efficacy of 0.2 to 0.4 IU/ml by the second day of treatment. Mean effective peak anti-Xa activity was 0.28 ± 0.06 IU/ml. Mean duration of anti-coagulation with LMWH was 25.8 ± 18 days. Ischemic strokes were observed in 3 patients (3.8%), with a total of 4 events. Three events occurred while on LMWH, and 1 event occurred during follow-up on oral anti-coagulation. There was 1 fatal stroke. No pump thrombus was observed. Major bleeding was observed in 5 patients (6.4%), with a total of 6 events. Gastrointestinal bleeding was the most common complication (n = 3). There were no fatal bleeding events. CONCLUSIONS: LMWH in the setting of LVAD shows rapid and constant biologic efficacy. Anti-coagulation with LMWH appears feasible after LVAD implantation. These findings support further evaluation of LMWH as an alternative to unfractionated heparin in this patient cohort.

Age and outcome after continuous-flow left ventricular assist device implantation as bridge to transplantation.

OBJECTIVE: The effect of age on outcomes after continuous-flow left ventricular assist device (LVAD) implantation as a bridge to transplantation (BTT) was determined. METHODS: From November 1998 to July 2007, 86 patients with advanced heart failure underwent continuous-flow LVAD implantation as BTT and were retrospectively analyzed. Patients were categorized into 2 groups by age at LVAD implantation: 56 patients (65.1%) younger than 60, Group 1; and 30 (34.9%) aged 60 years or older, Group 2. RESULTS: Group 2 patients had a higher incidence of heart failure caused by ischemic heart disease (63.3% vs 32.1%, p = 0.005) and more severely impaired renal function by Modification of Diet in Renal Disease-derived glomerular filtration rates (51.9 +/- 15.9 vs. 68.0 +/- 20.5 ml/min/1.73 m(2), p < 0.001) than Group 1. Age was the only independent predictor of post-LVAD death (hazard ratio, 1.4 p = 0.003). The BTT rate was lower (33.3% vs 62.5%, p = 0.010), and incidence of post-LVAD renal failure was higher (53.3% vs 30.4%, p = 0.037) in Group 2 vs Group 1. Post-LVAD survival at 1, 3, and 6 months was 92.9%, 79.9%, and 74.0% for Group 1 and 90.0%, 62.0%, and 37.0% for Group 2 (p = 0.007). Post-transplant survival at 1, 3, and 5 years was 87.8%, 82.3%, and 76.0% for Group 1 and 90.0%, 67.5%, 67.5% for Group 2 (p = 0.517). CONCLUSIONS: Patients aged 60 years and older have inferior post-LVAD survival; however, post-transplant survival is excellent. We advocate LVAD placement as bridge-to-transplant therapy only in carefully selected older patients most well suited for transplantation.