Five-Year Results of Coronary Artery Bypass Grafting With or Without Carotid Endarterectomy in Patients With Asymptomatic Carotid Artery Stenosis: CABACS RCT.

BACKGROUND: In patients with coronary artery disease and concomitant asymptomatic severe carotid stenosis, combined simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA) has been widely performed despite lack of evidence from randomized trials. We recently showed that the risk of stroke or death within 30 days was higher following CABG+CEA compared with CABG alone. Here, we report long-term outcomes following CABG with versus without CEA. METHODS: The CABACS (Coronary Artery Bypass Graft Surgery in Patients With Asymptomatic Carotid Stenosis Study) is a randomized, controlled, multicenter, open trial. Patients with asymptomatic severe (≥70%) carotid stenosis undergoing CABG were allocated either CABG+CEA or CABG alone, and follow-up was 5 years. Major secondary end points included nonfatal stroke or death, any death and any nonfatal stroke. Due to low recruitment, the study was stopped prematurely after randomization of 127 patients in 17 centers. RESULTS: By 5 years, the rate of stroke or death did not significantly differ between groups (CABG+CEA 40.6% [95% CI, 0.285-0.536], CABG alone 35.0% [95% CI, 0.231-0.484]; P=0.58). Higher albeit statistically nonsignificant rates of nonfatal strokes occurred at any time following CABG+CEA versus CABG alone (1 year: 19.3% versus 7.1%, P=0.09; 5 years: 29.4% versus 18.8%, P=0.25). All-cause mortality up to 5 years was similar in both groups (CABG+CEA: 25.4% versus CABG alone: 23.3%, hazard ratio, 1.148 [95% CI, 0.560-2.353]; P=0.71). Subgroup analyses did not reveal any significant effect of age, sex, preoperative modified Rankin Scale and center on outcome events. CONCLUSIONS: During 5-years follow-up, combined simultaneous CABG+CEA was associated with a higher albeit statistically nonsignificant rate of stroke or death compared with CABG alone. This was mainly due to a nonsignificantly higher perioperative risk following CABG+CEA. Since the power of our study was not sufficient, no significant effect of either procedure could be observed at any time during follow-up. REGISTRATION: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN13486906.

Safety of Simultaneous Coronary Artery Bypass Grafting and Carotid Endarterectomy Versus Isolated Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: The optimal operative strategy in patients with severe carotid artery disease undergoing coronary artery bypass grafting (CABG) is unknown. We sought to investigate the safety and efficacy of synchronous combined carotid endarterectomy and CABG as compared with isolated CABG. METHODS: Patients with asymptomatic high-grade carotid artery stenosis ≥80% according to ECST (European Carotid Surgery Trial) ultrasound criteria (corresponding to ≥70% NASCET [North American Symptomatic Carotid Endarterectomy Trial]) who required CABG surgery were randomly assigned to synchronous carotid endarterectomy+CABG or isolated CABG. To avoid unbalanced prognostic factor distributions, randomization was stratified by center, age, sex, and modified Rankin Scale. The primary composite end point was the rate of stroke or death at 30 days. RESULTS: From 2010 to 2014, a total of 129 patients were enrolled at 17 centers in Germany and the Czech Republic. Because of withdrawal of funding after insufficient recruitment, enrolment was terminated early. At 30 days, the rate of any stroke or death in the intention-to-treat population was 12/65 (18.5%) in patients receiving synchronous carotid endarterectomy+CABG as compared with 6/62 (9.7%) in patients receiving isolated CABG (absolute risk reduction, 8.8%; 95% confidence interval, -3.2% to 20.8%; PWALD=0.12). Also for all secondary end points at 30 days and 1 year, there was no evidence for a significant treatment-group effect although patients undergoing isolated CABG tended to have better outcomes. CONCLUSIONS: Although our results cannot rule out a treatment-group effect because of lack of power, a superiority of the synchronous combined carotid endarterectomy+CABG approach seems unlikely. Five-year follow-up of patients is still ongoing. CLINICAL TRIAL REGISTRATION: URL: https://www.controlled-trials.com. Unique identifier: ISRCTN13486906.

Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND: The risk of stroke after transfemoral aortic valve implantation (TAVI) due to dislodgement and subsequent embolization of debris from aortic arch atheroma or from the calcified valve itself ranges between 2% and 10%. The rate of clinically silent cerebral ischemia is unknown but may be even higher. METHODS AND RESULTS: Thirty-two patients who underwent TAVI with the use of a balloon-expandable (n=22) or self-expandable (n=10) stent valve prosthesis were included in this descriptive study and compared with a historical control group of 21 patients undergoing open surgical aortic valve replacement. Periprocedural apparent and silent cerebral ischemia was assessed by neurological testing and serial cerebral diffusion-weighted magnetic resonance imaging at baseline, at 3.4 (2.5 to 4.4) days after the procedure, and at 3 months. TAVI was successful in all patients. After the procedure, new foci of restricted diffusion on cerebral diffusion-weighted magnetic resonance imaging were found in 27 of 32 TAVI patients (84%) and were more frequent than after open surgery (10 of 21 patients [48%]; P=0.011). These lesions were usually multiple (1 to 19 per patient) and dispersed in both hemispheres in a pattern suggesting cerebral embolization. Volumes of these lesions were significantly smaller after TAVI than after surgery (77 [59 to 94] versus 224 [111 to 338] mm(3); P<0.001). There were neither measurable impairments of neurocognitive function nor apparent neurological events during the in-hospital period among TAVI patients, but there was 1 stroke (5%) in the surgical patient group. On 3-month follow-up diffusion-weighted magnetic resonance imaging, there were no new foci of restricted diffusion, and there was no residual signal change associated with the majority (80%) of the foci detected in the periprocedural period. CONCLUSIONS: Clinically silent new foci of restricted diffusion on cerebral magnetic resonance imaging were detected in almost all patients (84%) undergoing TAVI. Although typically multiple, these foci were not associated with apparent neurological events or measurable deterioration of neurocognitive function during 3-month follow-up. Further work needs to be directed to determine the clinical significance of these findings in a larger patient population.

Early and long-term cognitive outcome after conventional cardiac valve surgery.

Objectives: Adverse cognitive outcome is well recognized after coronary artery bypass grafting (CABG) while little is known about the extent and duration of decline after cardiac valve surgery. We investigated changes in cognitive function following conventional cardiac valve surgery over up to 4 years. Methods: Among 36 patients (65.2 ± 9.2 years, 36% women) who received valve surgery, we assessed serial cognitive function with a battery of 11 standardized tests across 3-4 years. Cognitive function was analysed to identify: (1) cognitive decline (i.e. within-patient changes in test scores) and (2) cognitive deficit (i.e. drop of score ≥1 SD in ≥3 tests). Diffusion-weighted magnetic resonance imaging (DW-MRI) was applied pre- and post-procedure to detect ischaemic brain injury. Data were compared to a historical cohort of 39 patients undergoing CABG. Results: After both valve surgery and CABG, a significant decline at discharge was detected in 7 of 11 cognitive tests. The rate of patients with a cognitive deficit after valve surgery vs CABG was 39% vs 56% at discharge, 14% vs 23% at 3 months, and 16% vs 26% at 3-4 years (not significant, [n.s.]). After valve surgery, DW-MRI identified 19 (53%) patients with evidence of 50 new focal ischaemic lesions (CABG: 20 [51%] patients with 42 lesions, n.s.). Cumulative cerebral ischaemic load per patient was not significantly different between the valve surgery group and CABG group (503 ± 485 mm 3 vs 415 ± 234 mm 3 ). After correction for multiple potential risk factors in both groups, reduced verbal memory at discharge could be identified as a predictor of long-term cognitive impairment in CABG patients only ( P = 0.04). For both the valve surgery and CABG group, no association between cognitive impairment and new ischaemic cerebral lesions was found. Conclusions: The course of cognitive performance after valve surgery and CABG was similar with early postoperative decline followed by subsequent recovery. Although silent small brain infarcts were present in about half of all patients, they did not impact cognitive performance neither at early nor during long-term follow-up.

Small ischemic brain lesions after cardiac valve replacement detected by diffusion-weighted magnetic resonance imaging: relation to neurocognitive function.

OBJECTIVE: Following coronary artery bypass graft surgery, some studies using magnetic resonance imaging (MRI) have demonstrated new small ischemic brain lesions in patients without apparent neurological deficits. We aimed to prospectively evaluate brain injury after cardiac valve replacement using MRI and to determine the relationship to neurocognitive function. METHODS: Thirty patients with a mean age of 64.9+/-9.8 years (range, 32-82, 12 female) receiving cardiac valve replacement (aortic valve replacement [AVR], n = 24; mitral valve replacement [MVR], n = 2; AVR and MVR, n = 2; AVR and mitral valve repair, n = 2) were investigated. Study protocol included neurological examination, comprehensive neuropsychological assessment and diffusion-weighted (DW) MRI. The investigations were performed before surgery and 5 days and 4 months after surgery. RESULTS: Postoperative DW MRI detected new focal brain lesions in 14 patients (47%). No patient revealed a focal neurological deficit. Six patients (43%) had multiple (> or = 3) lesions (range, 1-7). Lesion volume ranged from 50-500 mm3 except 1 territorial infarct of 1900 mm3. Of a total of 41 lesions, 27 (66%) were located in the right hemisphere and 32 in a subcortical location. By 5 days postoperatively, significant neurocognitive decline was observed in 5 of 13 tests affecting memory, attention and rate of information processing. By 4 months, dysfunction had recovered in all cognitive areas. The presence of new ischemic lesions was not associated with neurocognitive decline at discharge. There was also no significant correlation between clinical and operative variables and the presence of new DW lesions or neuropsychological outcome. CONCLUSIONS: Following cardiac valve replacement, new small ischemic brain lesions were detected by diffusion-weighted MRI. Neurocognitive decline was present early after operation, but resolved within 4 months. A correlation of new ischemic lesions to postoperative cognitive dysfunction or clinical variables was not found.

Evaluation of brain injury after coronary artery bypass grafting. A prospective study using neuropsychological assessment and diffusion-weighted magnetic resonance imaging.

OBJECTIVE: Neurocognitive dysfunction is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Studies using magnetic resonance imaging (MRI) have demonstrated that new focal brain lesions can occur after coronary artery bypass grafting (CABG), even in patients without apparent neurological deficits. Diffusion-weighted MRI is superior to conventional MRI and allows for sensitive and early detection of ischemic brain lesions. We prospectively investigated cerebral injury early and 3 months after CABG using diffusion-weighted MRI and related the findings to clinical data and neurocognitive functions. METHODS: Twenty-nine patients [67.6+/-8.6 (52-85) years, 5 females] undergoing elective CABG with CPB were examined before surgery, at discharge and 3 months after surgery. A battery of standardized neuropsychological tests and questionnaires on depression and mood were administered. Conventional and diffusion-weighted MRI of the brain was performed and new lesions were analyzed. Clinical characteristics, neuropsychological test performance and radiographic data were collected and compared. RESULTS: There was no major neurological complication after CABG. Thirteen patients (45%) exhibited 32 new ischemic lesions on postoperative diffusion-weighted MRI. The lesions were small, rounded and equally dispersed in both hemispheres. Eight patients had at least two lesions. At discharge, significant deterioration of neuropsychological performance was observed in 6 of the 13 tests compared to baseline assessment. By 3 months postoperatively, 5 of the 6 tests returned to preoperative levels. Verbal learning ability, however, remained impaired. The presence of new focal brain lesions was not associated with impaired neuropsychological performance. There was also no correlation between clinical variables, intraoperative parameters and postoperative complications and MRI findings. CONCLUSIONS: Although neurocognitive decline after CABG is mostly transient, memory impairment can persist for months. New ischemic brain lesions on postoperative diffusion-weighted MRI do not appear to account for the persistent neurocognitive decline.

Cognitive function after transapical aortic valve implantation: a single-centre study with 3-month follow-up.

OBJECTIVES: Reports on adverse neurological events following transcatheter aortic valve implantation (TAVI) have focused on strokes, while more subtle postoperative cognitive decline has not yet been systematically investigated. In this study, we prospectively examined neurological and cognitive outcomes in patients undergoing transapical (TA) and surgical aortic valve replacement (AVR). METHODS: A total of 64 patients with severe symptomatic aortic stenosis were investigated between January 2008 and July 2009. Clinical neurological examination and comprehensive neuropsychological testing were performed before and after the procedure, at discharge and at 3-month follow-up. Diffusion-weighted magnetic resonance imaging (DW-MRI) was applied to detect morphological brain injury. RESULTS: TA-TAVI patients (n = 27) were older and at higher surgical risk compared with surgical AVR patients (n = 37; mean age 82.2 ± 4.7 vs 67.5 ± 8.9 years; log EuroSCORE 36.4 ± 13.2 vs 2.6 ± 8.5%, both P <0.001). There was one stroke in each group (3.7 vs 2.7%, P = 0.49), both classified as embolic based on imaging characteristics. After TA-TAVI, cognitive tests showed no decline during follow-up, while, after AVR, 7 of 11 tests showed a decline early after surgery. Similarly, with-in patient analysis showed that the rate of individuals with clinically relevant cognitive decline was increased early after AVR (TA-TAVI vs AVR: 18 vs 46% at discharge [P = 0.03]; 28 vs 6% at 3 months [P = 0.04]). New focal ischaemic cerebral lesions were detected on DW-MRI in 58% (7 of 12) of patients after TA-TAVI vs 34% (12 of 35) after AVR (P = 0.13). The number of brain lesions per patient and cumulative embolic load per patient were similar between groups. An association between postoperative cerebral ischaemia and cognitive dysfunction was not found (odds ratio 2.37, 95% confidence interval 0.05-113.75, P = 0.66). CONCLUSIONS: Cognitive function was only mildly impaired after TA-TAVI when compared with a marked, albeit transient, decline after surgical AVR. Focal embolic brain injury tended to occur more frequently after TA-TAVI, but this was not related to cognitive decline during the 3-month follow-up.

Cognitive outcomes three years after coronary artery bypass surgery: relation to diffusion-weighted magnetic resonance imaging.

BACKGROUND: Cognitive decline is well recognized early after coronary artery bypass graft surgery (CABG), but controversy exists regarding the degree and duration of these changes. We investigated the course of cognitive performance during 3 years after surgery and determined whether ischemic brain injury detected by diffusion-weighted magnetic resonance imaging was related to cognitive decline. METHODS: Thirty-nine patients undergoing on-pump CABG completed preoperative neuropsychologic examination and were followed up prospectively at discharge, 3 months, and 3 years after surgery. Cognitive performance was assessed with a battery of 11 standardized psychometric tests assessing 7 cognitive domains. Cognitive outcome was analyzed by determining (1) mean changes in within-patient scores over time (identifying cognitive functions with decline), and (2) the incidence of cognitive deficit for each individual (identifying patients with decline). Objective evidence of acute cerebral ischemia was obtained by diffusion-weighted magnetic resonance imaging. Prospectively collected data were used to identify predictors of cognitive deficits. RESULTS: From baseline to discharge, cognitive test scores significantly declined in 7 measures. Most tests improved by 3 months. Between 3 months and 3 years, late decline was observed in 2 measures with persistent deterioration in 1 measure (verbal memory) relative to baseline. Postoperative cognitive deficits (drop of > or = 1 SD in scores on > or = 3 tests) were observed in 56% of patients at discharge, 23% at 3 months and 31% at 3 years. On postoperative diffusion-weighted magnetic resonance imaging, there were new ischemic cerebral lesions in 51% of patients. The presence of cognitive deficit at discharge was a significant univariate predictor of late cognitive decline (p = 0.025). A relation between the presence of new diffusion-weighted magnetic resonance imaging detected lesions and cognitive decline, however, was not found. CONCLUSIONS: Longitudinal cognitive performance of patients with CABG showed a two-stage course with early improvement followed by later decline. Long-term cognitive deficit was predicted by early cognitive decline, but not by ischemic brain lesions on magnetic resonance imaging.