Ioannis K. Toumpoulis

European system for cardiac operative risk evaluation predicts long-term survival in patients with coronary artery bypass grafting

OBJECTIVE To evaluate the accuracy of predicting long-term mortality in patients with coronary artery bypass grafting (CABG) by using the European system for cardiac operative risk evaluation (EuroSCORE). METHODS Medical records of patients with CABG (n=3760) between January 1992 and March 2002 were retrospectively reviewed and their predicted surgical risk was calculated according to the standard (study A) and logistic (study B) EuroSCORE. In study A the patients were divided into six groups: 0-2 (n=610), 3-5 (n=1479), 6-8 (n=1099), 9-11 (n=452), 12-14 (n=103) and >14 (n=17). In study B the patients were divided into seven groups: 0.00-2.00 (n=447), 2.01-5.00 (n=1190), 5.01-10.00 (n=890), 10.01-20.00 (n=686), 20.01-30.00 (n=234), 30.01-60.00 (n=254) and >60.00 (n=59). Long-term survival was obtained by the National Death Index and Kaplan-Meier curves were constructed and compared employing the log-rank test. Multivariate Cox regression analysis was performed in order to control for pre, intra and postoperative factors and adjusted hazard ratios were calculated for standard and logistic EuroSCORE groups. The receiver operating characteristic (ROC) curves were plotted to assess the discrimination ability of the EuroSCORE. RESULTS In study A there were differences among the six groups in 30-day mortality (0.7%, 1.0%, 3.1%, 4.6%, 13.6% and 23.5%; P<0.001), in major complications (8.5%, 10.4%, 16.2%, 20.4%, 31.1% and 35.3%; P<0.001) as well as in actuarial long-term survival (86.2%, 79.6%, 53.6%, 37.9%, 24.9% and 0% from EuroSCORE 0-2 to >14; P<0.001). In study B there were differences among the seven groups in 30-day mortality (0.9%, 1.1%, 1.2%, 3.6%, 3.4%, 8.7% and 15.3%; P<0.001), major complications (8.5%, 10.1%, 12.1%, 18.4%, 16.2%, 26.0% and 30.5%; P<0.001) as well as in actuarial long-term survival (89.5%, 79.9%, 66.9%, 51.0%, 40.3%, 38.4% and 13.7% from EuroSCORE 0.00-2.00 to >60.00; P<0.001). Multivariate Cox regression analysis confirmed that EuroSCORE (standard or logistic) was a statistically significant predictor for long-term mortality, while the area under the ROC curve was 0.72 for either standard or logistic EuroSCORE. CONCLUSION The predicted surgical risk in CABG patients as calculated by standard or logistic EuroSCORE is a strong predictor for long-term survival in addition to predicting operative survival for which it was originally designed.

Injection of isolated mitochondria during early reperfusion for cardioprotection

Previously, we demonstrated that ischemia induces mitochondrial damage and dysfunction that persist throughout reperfusion and impact negatively on postischemic functional recovery and cellular viability. We hypothesized that viable respiration-competent mitochondria, isolated from tissue unaffected by ischemia and then injected into the ischemic zone just before reperfusion, would enhance postischemic functional recovery and limit infarct size. New Zealand White rabbits (n = 52) were subjected to 30 min of equilibrium and 30 min of regional ischemia (RI) induced by snaring the left anterior descending coronary artery. At 29 min of RI, the RI zone was injected with vehicle (sham control and RI vehicle) or vehicle containing mitochondria (7.7 x 10(6) +/- 1.5 x 10(6)/ml) isolated from donor rabbit left ventricular tissue (RI-Mito). The snare was released at 30 min of RI, and the hearts were reperfused for 120 min. Our results show that left ventricular peak developed pressure and systolic shortening in RI-Mito hearts were significantly enhanced (P < 0.05 vs. RI-vehicle) to 75% and 83% of equilibrium value, respectively, at 120 min of reperfusion compared with 57% and 62%, respectively, in RI-vehicle hearts. Creatine kinase-MB, cardiac troponin I, and infarct size relative to area at risk were significantly decreased in RI-Mito compared with RI-vehicle hearts (P < 0.05). Confocal microscopy showed that injected mitochondria were present and viable after 120 min of reperfusion and were distributed from the epicardium to the subendocardium. These results demonstrate that viable respiration-competent mitochondria, isolated from tissue unaffected by ischemia and then injected into the ischemic zone just before reperfusion, significantly enhance postischemic functional recovery and cellular viability.

Postoperative and Long-Term Outcome of Patients With Chronic Obstructive Pulmonary Disease Undergoing Coronary Artery Bypass Grafting

BACKGROUND Chronic obstructive pulmonary disease (COPD) has been conventionally associated with increased operative mortality and morbidity after coronary artery bypass grafting. Some studies, however, challenge this association. Moreover, the effect of COPD on long-term survival after coronary artery bypass grafting has not been adequately assessed. Thus, in this clinical setting, both early and late outcome require further examination. METHODS We studied 3,760 consecutive patients who underwent isolated coronary artery bypass grafting between 1992 and 2002. The propensity for COPD was determined by logistic regression analysis, and each patient with COPD was matched with 3 patients without COPD. Matched groups were compared for early outcome and long-term survival (mean follow-up, 7.6 years). Long-term survival data were obtained from the National Death Index. RESULTS There were 550 patients (14.6%) with COPD. Multivariate analysis showed that patients with COPD were older and sicker. However, propensity-matched groups did not differ in terms of hospital mortality or major morbidity, although COPD was associated with a slightly longer hospital stay. In contrast, COPD patients had increased long-term mortality, with a hazard ratio of 1.28 (95% confidence intervals, 1.11 to 1.47; p=0.001). Freedom from all-cause mortality at 7 years after CABG was 65% and 72% in matched patients with and without COPD, respectively (p=0.008). In patients with COPD, the hazard estimate was consistently increased up to 9 years postoperatively. CONCLUSIONS Chronic obstructive pulmonary disease, although not an independent predictor of increased early mortality and morbidity in this series, is a continuing detrimental risk factor for long-term survival.

Latent arterial hypertension in apparently lone atrial fibrillation.

Introduction. Longitudinal studies on lone AF are rare and the incidence of hypertension in this population unknown. This study aimed at investigating the incidence of arterial hypertension in patients with apparently lone atrial fibrillation (AF).Methods and Results. Out of 292 consecutive patients presented with permanent or paroxysmal AF, 32 patients were diagnosed as having lone AF according to strict criteria. Three patients were subjected to ablation of the ligament of Marshall, 14 patients to pulmonary vein isolation, and the remainder were treated with beta blockade. Patients were followed-up for a 1–3 year period. During follow-up, 14 patients were diagnosed as having arterial hypertension. Thirteen of them had recurrent AF despite ligament of Marshall ablation (1 patient), pulmonary vein isolation (4 patients) and beta blockade (8 patients). Cox regression analysis revealed that the only significant predictor of development of hypertension was complete or partial response to antiarrhythmic therapy (beta = 3.82, S.E. = 1.22, exp(b) = 45.63, 95% C.I. = 4.17–499.2, p = 0.001), independent of age (beta = −0.01, p = 0.74), sex (beta = −0.91, p = 0.28), left ventricular ejection fraction (beta = 0.06, p = 0.52), left atrial size (beta = 0.58, p = 0.7) and kind of antiarrhythmic therapy (ablation or drug therapy) (beta = 1.36, p = 0.09). In patients with lone AF that did not respond at all to antiarrhythmic therapy, there was a 45.6 times higher risk of diagnosing hypertension during the next 3 years as compared to responders.Conclusion. Approximately 44% of patients with an initial diagnosis of lone AF may represent occult cases of arterial hypertension. In these patients hypertension may affect AF recurrence and treatment outcomes, regardless of the mode of antiarrhythmic therapy used.

Impact of Early and Delayed Stroke on In-Hospital and Long-Term Mortality After Isolated Coronary Artery Bypass Grafting

Stroke after coronary artery bypass grafting (CABG) is an infrequent, yet devastating complication with increased morbidity and mortality. We sought to determine risk factors for early (intraoperatively to 24 hours) and delayed (>24 hours to discharge) stroke and to identify their impact on long-term mortality after CABG. We studied 4,140 consecutive patients who underwent isolated CABG from 1992 to 2003. Long-term survival data (mean follow-up 7.4 years) were obtained from the National Death Index. Independent predictors for stroke and in-hospital mortality were determined by multivariate logistic regression analysis including all available preoperative, intraoperative, and postoperative risk factors. Independent predictors for long-term mortality were determined by multivariate Cox regression analysis. One hundred two patients (2.5%) developed early stroke and 36 patients (0.9%) delayed stroke. Independent predictors for early stroke were age, recent myocardial infarction, smoking, femoral vascular disease, body mass index, reoperation for bleeding, postoperative sepsis and/or endocarditis, and respiratory failure, whereas those for delayed stroke were female gender, white race, preoperative renal failure, respiratory failure, and postoperative renal failure. Early stroke was an independent predictor for in-hospital (odds ratio 3.49, 95% confidence interval [CI] 1.56 to 7.80, p = 0.002) and long-term (hazard ratio 1.70, 95% CI 1.30 to 2.21, p <0.001) mortalities. Delayed stroke was not an independent predictor for in-hospital (odds ratio 0.90, 95% CI 0.23 to 3.51, p = 0.878) or long-term (hazard ratio 0.66, 95% CI 0.38 to 1.17, p = 0.156) mortality. In conclusion, risk factors for early in-hospital stroke differ from those of delayed in-hospital stroke after CABG. Early stroke is an independent predictor for in-hospital and long-term mortalities, suggesting the need for a more frequent follow-up and appropriate pharmacologic therapy after discharge.

Differential Expression of Collagen Type V and XI α-1 in Human Ascending Thoracic Aortic Aneurysms

BACKGROUND The molecular mechanisms leading to ascending thoracic aortic aneurysms (ATAAs) remain unknown. We hypothesized that alterations in expression levels of specific fibrillar collagens occur during the aneurysmal process. METHODS Surgical samples from ascending aortas from patients with degenerative ATAAs were subdivided by aneurysm diameter: small, 5 to 6 cm; medium, 6 to 7 cm; and large, greater than 7 cm; and compared with nonaneurysmal aortas (mean diameter, 2.3 cm). RESULTS Histology, immunofluorescence, and electron microscopy demonstrated greater disorganization of extracellular matrix constituents in ATAAs as compared with control with an increase in collagen alpha1(XI) within regions of cystic medial degenerative lesions. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed collagens type V and alpha1(XI) were significantly and linearly increased in ATAAs as compared with control (p < 0.001). There was no change in the messenger ribonucleic acid (mRNA) expression levels of collagens type I and III. Western blot analysis showed collagens type I and III were significantly decreased and collagens alpha1(XI) and V were significantly increased and were linearly correlated with the size of the aneurysm (p < 0.001 for both). CONCLUSIONS These results demonstrate that increased collagen alpha1(XI) and collagen V mRNA and protein levels are linearly correlated with the size of the aneurysm and provide a potential mechanism for the generation and progression of aneurysmal enlargement.

A Novel Drill Set for the Enhancement and Assessment of Robotic Surgical Performance

BACKGROUND There currently exist several training modules to improve performance during video-assisted surgery. The unique characteristics of robotic surgery make these platforms an inadequate environment for the development and assessment of robotic surgical performance. METHODS Expert surgeons (n=4) (>50 clinical robotic procedures and >2 years of clinical robotic experience) were compared to novice surgeons (n=17) (<5 clinical cases and limited laboratory experience) using the da Vinci Surgical System. Seven drills were designed to simulate clinical robotic surgical tasks. Performance score was calculated by the equation Time to Completion + (minor error) x 5 + (major error) x 10. The Robotic Learning Curve (RLC) was expressed as a trend line of the performance scores corresponding to each repeated drill. RESULTS Performance scores for experts were better than novices in all 7 drills (p<0.05). The RLC for novices reflected an improvement in scores (p<0.05). In contrast, experts demonstrated a flat RLC for 6 drills and an improvement in one drill (p=0.027). CONCLUSION This new drill set provides a framework for performance assessment during robotic surgery. The inclusion of particular drills and their role in training robotic surgeons of the future awaits larger validation studies.

Harvesting Radial Artery and Neurologic Complications

Abstract  Background: Determination of the incidence, mechanisms, and diagnosis of hand complications after radial artery (RA) harvesting in coronary surgery (CABG). Methods: The study group (RA group) includes 54 patients who underwent RA harvesting in CABG operation. The control group (noRA group) consists of 131 patients who underwent CABG without the use of RA graft. The average follow‐up time was 16.36 ± 5.13 months. The patients were examined clinically, (a) for motor function abnormalities associated with radial and median nerve damage and (b) for sensory abnormalities, and the function of radial nerve was determined by eliciting the brachioradialis reflex. They answered in a formal scripted questionnaire to elicit symptoms and clinical points attributable to nerve damage during RA harvest, such as hand weakness, thumb weakness, sensation abnormalities on the back and on the palm side of the forearm, hand numbness, hand‐reversible paresis or forearm infection postoperatively, and any other upper limb abnormality.Results: Of the patients in the RA group, 34.09% reported left‐hand abnormality after operation. On the other hand, in the noRA group left‐hand abnormality was reported in 18.68% of patients. In the RA group sensation abnormality was reported in 34.09% of patients and thumb weakness alone was reported in 6.82% of patients. There was a statistically significant difference between the two groups. Low EuroSCORE was the predicting factor for motor abnormalities. Conclusions: More knowledge has been added about the neurologic complications after RA harvesting lately. We demonstrated the rate of motor and sensory abnormality, the potential mechanisms of these complications caused by surgical trauma or devascularization, and any predictive factors of complications. Optimal surgical techniques to avoid the damage of the responsible nerves are recommended.

Peripheral blood lymphocytes from patients with bipolar disorder demonstrate apoptosis and differential regulation of advanced glycation end products and S100B

Abstract Background: This study addresses the expression of the glycosylated proteins known as advanced glycation end products (AGEs), the calcium binding protein S100B and the apoptotic parameters cytochome c and caspase-3 activity in peripheral lymphocyte cytosolic extracts from a sample of bipolar disorder (BD) patients and healthy (control) subjects. Methods: Cross-sectional study of 35 patients with a clinical diagnosis of bipolar disease (10 euthymic, 12 depressed, 13 manic) and 10 healthy control subjects. Lymphocytes were used as a surrogate model in BD diagnosis and treatment. AGEs and S100B in lymphocyte cell extracts were measured by commercially available enzyme-linked immunosorbent assay. Results: AGEs were lower in all BD patients compared to healthy subjects. Depressed patients had approximately two-fold higher S100B levels compared to healthy subjects. Manic and depressed BD patients had increased superoxide dismutase mRNA levels. Apoptosis as measured by BAX/Bcl2 ratio, cytochrome c release, caspase-3 activity was increased in manic and depressed patients compared to healthy subjects. In the depressed patients, S100B levels correlated with cytochrome c release. Conclusions: In conclusion, our study shows decreased AGEs and increased S100B levels and caspase down-stream apoptosis in peripheral lymphocytes of BD patients that may underlie disease etiopathogenesis.

External validation of the modified Thoracoscore in a new thoracic surgery program: prediction of in-hospital mortality

Informed consent prior to any surgical intervention should include in-hospital survival estimation after the procedure performed. The recently developed Thoracoscore predicts well the postoperative mortality possibility. The purpose of our study was to test the modified Thoracoscore performance in our new thoracic program. One hundred and fifty-five consecutive patients underwent thoracic surgery procedure within two years. The procedures performed were: 62 lung resections, 10 open tumor biopsies, 21 neck and mediastinal procedures, 33 chest wall and pleural procedures, 8 tracheal procedures, 3 esophageal procedures, 13 minor cardiac procedures, and 5 chest trauma cases. The modified Thoracoscore was calculated based on the following variables: age, gender, priority of the procedure, malignancy, type of procedure, Zubrod score, ASA class, and number of co-morbidities. The observed mortality was 5.2% (eight deaths) while the predicted one based on the modified Thoracoscore was 4.9%. The scoring system we used had excellent discriminatory ability with a C statistic (0.95, 95% CIs 0.91-0.99). The Hosmer-Lemeshow goodness-of-fit was not statistically significant (P=0.82), indicating acceptable calibration of the model for the present series. The modified Thoracoscores ability to predict postoperative survival in the whole context of thoracic surgery performs well in our program. Application of any risk scoring system requires external validation and provides comparison of the actual outcomes with other programs.