The Relevance of Postoperative Cognitive Decline in Daily Living: Results of a 1-Year Follow-up.

OBJECTIVES: Postoperative cognitive decline (POCD) has a perceivable influence on daily living and is noticed more often by close relatives than by patients themselves 3 months after aortic valve replacement. This study aimed to elucidate the longitudinal course of the subjective awareness of POCD. DESIGN: Follow-up of a prospective observational study. SETTING: A single cardiothoracic center in Germany. PARTICIPANTS: The study included 108 patients scheduled for elective aortic valve replacement surgery and 85 close relatives of the patients. INTERVENTIONS: In addition to conducting a neuropsychologic examination, the authors previously interviewed 82 patients with a Cognitive Failure Questionnaire for self-assessment (s-CFQ), and 62 relatives with the Cognitive Failure Questionnaire for others (f-CFQ) before and 3 months after surgery. Up until 12 months after surgery, the authors continuously interviewed additional patients (baseline and 3 months after surgery), thereby enlarging the original sample, and included the entire group (108 patients, 85 relatives) for the 12-month follow-up. RESULTS: The analysis showed that relatives (p = 0.026) and patients experienced patients' cognitive decline 3 months after surgery (p = 0.009). All changes still were observed in questions related to memory and attention. After 1 year, the s-CFQ no longer differed between baseline and postoperative assessment. Mean scores in the f-CFQ still were above baseline, barely missing statistical significance (p = 0.051). In patients with "change to worse" in the f-CFQ at 1-year follow-up, declining cognitive results in nonverbal learning (p = 0.021) could be observed 3 months postoperatively. Only a decrease in 3-month f-CFQ correlated with a decline in specific neuropsychologic tests 3 months after surgery. CONCLUSIONS: Contrary to the authors' previous results, the impact of POCD on daily living functions also was recognized by the patients themselves. The long-term influence and the associations between subjective deficits and psychometric cognitive measures seemed to be assessed more reliably by close relatives.

Cortisol awakening and stress response, personality and psychiatric profiles in patients with takotsubo cardiomyopathy.

OBJECTIVE: Alterations in cortisol awakening and stress responses (CAR, CSR) are sensitive markers for the basal activity and responsiveness of the hypothalamus-pituitary-adrenal axis (HPAA) in psychopathological conditions. We investigated whether patients with takotsubo cardiomyopathy (TTC) differ in these markers when compared with non-ST-segment elevation myocardial infarction (NSTEMI) patients and healthy controls. METHODS: 19 female TTC patients were compared with 20 female NSTEMI patients and with 20 healthy women, matched by age and index event date. Salivary sampling indicated cortisol release, questionnaires assessed personality, life events, chronic stress and psychiatric symptoms. RESULTS: The groups did not differ relevantly in their basal HPAA activity, psychiatric or personality profiles. Despite increased heart rates in response to stress (median difference (MDdiff)=3.5, p=0.002) and higher nervousness scores (MDdiff=-3.0, p=0.024), TTC patients revealed a blunted CSR with a medium effect compared to the controls (MDdiff=-3.2 nmol/L, p=0.022, r=0.36); even when controlled for prestress cortisol differences (p=0.044, r=0.33). In comparison with NSTEMI patients, no significant differences in CSR (MDdiff=-1.9 nmol/L, p=0.127, r=0.25) or nervousness (MDdiff=2.0, p=0.107) can be observed. Stressful life events, for example, traumatic experiences, occurred more often in TTC (42%) than in NSTEMI patients and controls (both 10%, p=0.031). CONCLUSIONS: In this small exploratory trial, a trend for a blunted CSR and high incidences of stressful life events were observed in TTC patients. If these results can be confirmed in larger studies, chronic stress and the inhibitory influence of cortisol on catecholamine release might be significant for the pathogenesis of TTC.

Flat-panel volumetric computed tomography in cerebral perfusion: evaluation of three rat stroke models.

Flat-panel volumetric computed tomography (fpVCT) is a non-invasive approach to three-dimensional small animal imaging. The capability of volumetric scanning and a high resolution in time and space enables whole organ perfusion studies. We aimed to assess feasibility and validity of fpVCT in cerebral perfusion measurement with impaired hemodynamics by evaluation of three well-established rat stroke models for temporary and permanent middle cerebral artery occlusion (MCAO). Male Wistar rats were randomly assigned to temporary (group I: suture model) and permanent (group II: suture model; III: macrosphere model) MCAO and to a control group. Perfusion scans with respect to cerebral blood flow (CBF) and volume (CBV) were performed 24h post intervention by fpVCT, using a Gantry rotation time of 1s and a total scanning time of 30s. Postmortem analysis included infarct-size calculation by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Infarct volumes did not differ significantly throughout intervention groups. After permanent MCAO, CBF significantly decreased in subcortical regions to 78.2% (group II, p=0.005) and 79.9% (group III, p=0.012) and in total hemisphere to 77.4% (group II, p=0.010) and 82.0% (group III, p=0.049). CBF was less impaired with temporary vessel occlusion. CBV measurement revealed no significant differences. Results demonstrate feasibility of cerebral perfusion quantification in rats with the fpVCT, which can be a useful tool for non-invasive dynamic imaging of cerebral perfusion in rodent stroke models. In addition to methodological advantages, CBF data confirm the macrosphere model as a useful alternative to the suture model for permanent experimental MCAO.

Ultrasound destruction of air microemboli as a novel approach to brain protection in cardiac surgery.

OBJECTIVE: Evaluation of a novel approach to eliminate air microemboli from extracorporeal circulation via ultrasonic destruction. DESIGN: In vitro proof-of-concept study. SETTING: Research laboratory. PARTICIPANTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An extracorporeal circulation device was filled with human blood circulating at 3 L/min. Air bubbles were injected into the system. For bubble destruction, the blood in the tubing system was repeatedly insonated for 3 minutes using a therapeutic 60-kHz device, with variation of intensity and duty cycle settings, ranging from 0.2 W/cm² to 1.0 W/cm² and from duty cycle 60% to continuous wave (CW). Number and diameter of air microemboli were counted upstream and downstream of the ultrasound device by a 2-channel microemboli Doppler detector. For safety assessment, circulating blood was insonated continuously for 2 hours at 0.8 W/cm² CW and compared with circulation without insonation; and standard blood parameters were analyzed. Without treatment, 1,313 to 1,580 emboli were detected upstream, diameter ranging between 10 and 130 µm. Ultrasound treatment eliminated up to 87% of all detected bubbles in cw application (p<0.01) and showed comparable effects at intensities from 0.4 W/cm² to 1.0 W/cm² cw. Bubbles sized>15 µm almost were eliminated completely (p<0.001). Pulsed wave application rendered inferior results (p>0.05). No relevant changes of blood parameters were observed compared with control circulation. CONCLUSIONS: Ultrasound destruction of air emboli is a very efficient method to reduce number and size of emboli. Within the limits of safety assessment, the authors could not detect relevant side effects on standard blood parameters.

Subjective impairment after cardiac surgeries: the relevance of postoperative cognitive decline in daily living.

OBJECTIVES: Postoperative cognitive decline (POCD) is a frequent complication after cardiac surgeries. It remains unclear how relevant this decline in psychometric results is for daily life. The aim of the study was to assess cognitive failures, as seen by patients and close relatives, on a quantitative level. METHODS: In addition to an extensive neuropsychological test battery, we interviewed 82 patients with a modified version of the self-assessment cognitive failure questionnaire (s-CFQ) and 62 close relatives (mostly spouses) with the CFQ-for-others version (f-CFQ) before and 3 months after aortic valve replacement. The questionnaires evaluate the frequency of failures in daily living related to memory, attention, action and perception. RESULTS: POCD occurred in all tests that had been applied to assess declarative memory functions; the mean performance dropped from baseline in these tests (P-values ranging from 0.033 and <0.001). The s-CFQ did not differ between baseline and postoperative assessment [baseline: mean 37.60, standard deviation (SD) 14.38; post: mean 36.22, SD 12.29] (t(0.05, 76) = 1.17; P = 0.246). However, the assessment by others was worse in the f-CFQ after surgery (baseline: mean 8.02, SD 4.51; post: mean 9.58, SD 6.11) (t(0.05, 61) = 2.61; P = 0.012). All changes were observed in questions related to memory and attention failures only. Higher (worse) rates in f-CFQ change scores correlated with neuropsychological change scores, namely in pictorial memory (mistakes) (r = 0.35; P = 0.003) and word fluency (correct answers) (r = -0.29; P = 0.014). Additionally, those patients with worse f-CFQ change scores (>1 SD) from baseline had clearly worse outcomes in word fluency (t(0.05, 60) = 2.53; P = 0.007) and non-verbal learning (t(0.05, 60) = 2.66; P = 0.005). The effects remained significant when controlled for depression/anxiety scores. CONCLUSIONS: The result demonstrates that cognitive side-effects could have a perceivable impact on daily living functions. However, slight deficits are more realized by others than by the patients themselves. Correlations between ratings by others and psychometric cognitive measures indicate that assessment by others is more reliable than self-assessment.

Cognitive decline and ischemic microlesions after coronary catheterization. A comparison to coronary artery bypass grafting.

BACKGROUND: Postinterventional cognitive dysfunction (PICD) is a known complication of coronary artery bypass grafting (CABG). However, it is largely unknown whether PICD occurs after coronary catheterization. METHODS: Neuropsychologic data were obtained from 37 patients who received coronary catheterization and 47 patients who underwent elective CABG at baseline and 3 months after the interventions. The outcomes were contrasted to 33 healthy volunteers, using analysis of covariance with baseline scores as covariates. Cerebral magnetic resonance imaging with diffusion-weighted imaging (DWI) sequences was performed in 30 catheter and 39 CABG patients 2 to 4 days after the procedures. RESULTS: The rate of acute ischemic lesions amounted to 3.3% in the catheter group and to 17.9% in the CABG group. Postinterventional cognitive dysfunction was detected in 2 (of 10) tests in the catheter group as compared with the healthy controls (verbal memory: total recall, t = -2.61 (P = .005) and nonverbal memory, t = -2.60 [P = .005]). The CABG group showed PICD in 7 of 10 tests as compared with the healthy controls (statistics ranging from t = -1.95 [P = .027] to t = -5.14 [P < .001]). Scores of depression/anxiety and health-related quality of life were not associated with PICD (P > .05). CONCLUSIONS: As compared with CABG, PICD and cerebral lesions appear to be substantially milder after coronary catheter intervention, but not negligible.

Neuropsychological decline after catheter ablation of atrial fibrillation.

BACKGROUND: Cerebral embolic events represent recognized side effects after catheter ablation in the treatment of recurrent atrial fibrillation (AF). OBJECTIVE: The study was performed to analyze the neuropsychological outcome and to detect new embolic ischemic brain lesions after therapeutic left atrial catheter ablation of AF. METHODS: We enrolled 23 patients with recurrent AF who underwent elective circumferential pulmonary vein isolation. The primary endpoint was the neuropsychological outcome 3 months after intervention in contrast to the results of non-AF controls (n = 23) without ablation and in covariance of baseline performance. Cerebral diffusion-weighted magnetic resonance imaging (DWI) was performed in 21 AF patients at baseline, 2-4 days, and 3 months after intervention. RESULTS: In 3/21 patients (14.3%), new ischemic lesions were detected on DWI shortly after intervention. In one patient, a territorial middle cerebral artery infarct occurred with severe clinical symptoms. The other two patients represented clinically silent small lesions. In contrast to the control group and in covariance of baseline performance, the ablation group showed worse neuropsychological outcome in verbal memory (one of five cognitive domains) with an effect size of d = 0.93[t (.05; 42) = -3.53; P < .001; false discovery rate (FDR)(crit) ≤ .01]. CONCLUSION: Adverse neuropsychological changes after left atrial catheter ablation are verifiable in verbal memory and, conjoined with ischemic brain lesions on DWI, might represent cerebral side effects of this procedure.

Evaluation of methods to predict early long-term neurobehavioral outcome after coronary artery bypass grafting.

Postoperative cognitive decrease (POCD) represents the most frequent complication in modern cardiac surgery. The application of easily assessable surrogate parameters that predict long-term POCD at early time points is tempting. The aim of the present study was to analyze the predictive value of cerebral biomarkers, diffusion-weighted magnetic resonance imaging (DWI), and cognitive bedside testing after coronary artery bypass grafting (CABG). From 106 patients who underwent elective CABG, blood samples were drawn for the measurement of protein S100B and neuron-specific enolase release at baseline, at the end of surgery, and 48 hours afterward. Cerebral DWI was carried out before and 2 to 4 days after surgery. Cognitive functioning was assessed before, 2 to 4 days (bedside testing) after, and 3 months after CABG. On DWI, lesions were detected in 15.1% of patients. Biomarker levels and the presence of acute ischemic lesions on DWI were not associated with long-term POCD. Early POCD was correlated with 3-month POCD (r = 0.46, p <0.001). Ninety-one percent of patients who had shown moderate to severe POCD (<-1.5 z scores) in the early phase still had decreased memory functioning at 3 months compared to baseline (likelihood ratio 5.23). Early POCD was asserted as the only predictor for long-term POCD in a stepwise multiple linear regression model (R(2) = 0.20, p <0.001), excluding age, length of surgery, aortic clamping and cardiopulmonary bypass duration, the number of anastomoses, and postoperative neuron-specific enolase and S100B levels. In conclusion, the results show that in contrast to biomarkers, DWI, age, or intraoperative variables, early neuropsychological bedside testing predicts long-term POCD after CABG with acceptable accuracy.

Protecting the brain from gaseous and solid micro-emboli during coronary artery bypass grafting: a randomized controlled trial.

AIMS: The purpose of the study was to investigate whether intra-operative filter devices protect the brain during coronary artery bypass grafting (CABG) and to determine the impact of solid and gaseous micro-emboli on neuropsychological functioning. METHODS AND RESULTS: Patients undergoing CABG received either an intra-aortic filter (Embol-X) (n = 43), designed to reduce solid micro-emboli, a dynamic bubble trap (DBT) (n = 50), designed to reduce gaseous micro-emboli, or no additional device (control group) (n = 50). Cognitive functioning was assessed before and 3 months after CABG. Micro-emboli signals (MES) were detected during surgery using transcranial Doppler (TCD) sonography. Cerebral magnetic resonance imaging (MRI) was carried out before and after surgery. Primary endpoint was the cognitive outcome of the filter groups compared with the controls. Analysis of covariance was performed using the post-operative cognitive test scores as continuous variables in covariance of the corresponding pre-operative scores. Secondary endpoints were the MES rates and the number of acute ischaemic lesions after CABG. Compared with the controls, cognitive functioning of the DBT group was better in executive functioning (t = 2.525, P = 0.0065) and verbal short-term memory (t = 2.420, P = 0.009). The Embol-X group did not perform better in any test. The total number of MES was lower in the DBT group (median 99, P = 0.0019), but not in the Embol-X group (median 162.5, P > 0.05), both compared with controls (median 164.5). After surgery, 17 patients displayed small ischaemic brain lesions on MRI with equal distribution between the groups. CONCLUSION: Gaseous micro-embolization contributes to neuropsychological decline, which is measurable 3 months post-operatively. No filter device could protect the brain during CABG completely. However, the use of the DBT tends to improve the cognitive outcome after CABG. Gas filters are recommendable for neuroprotection during cardiac surgery.