Prediction of surgical outcome after aortic valve replacement.

BACKGROUND: Aortic valve replacement has some major adverse outcomes. For these, the predictors need identification. METHODS: This was a retrospective file study of 1000 consecutive patients who underwent AVR for degenerative aortic valve disease. Twenty-five preoperative and 5 peroperative factors were screened by a univariate Fisher-exact analysis. The predictors were identified in a second step by logistic regression multivariate analysis. RESULTS: Five hundred thirty patients were male. The mean age was 75 (71-77) years and 610 also underwent CABG. For hospital mortality, need for urgent aortic valve replacement (p < 0.001) was the dominant predictor. Need for digitalis (p = 0.002) and age > 80 (p = 0.005) followed. For postoperative congestive heart failure, need for urgent aortic valve replacement was also dominant (p <0.001). Atrial fibrillation (p = 0.001,) and ejection fraction < 50% (p = 0.055) were less important. For ventricular arrhythmia, previous infarction (p = 0.025) and ejection fraction < 50% (p = 0.032) were identified. For bleeding, concomitant CABG (p = 0.046) and chronic obstructive pulmonary disease were identified. For thromboembolic events only an ejection fraction < 50% (p = 0.027) was identified. CONCLUSIONS: Need for urgent aortic valve replacement is the dominant predictor for postoperative mortality and congestive heart failure. Once a degenerative aortic valve disease becomes symptomatic, prompt referral could prevent the development for need for urgent surgery, with all its adverse postoperative consequences.

A thousand pericardial valves in aortic position: risk factors for postoperative acute renal function impairment in elderly.

AIM: Postoperative renal dysfunction after aortic valve replacement is a serious complication. To minimize its occurrence, risk factors have to be identified, and if possible eliminated. METHODS: Of 1000 consecutive patients, who underwent AVR, a file study was performed chi(2)nd logistic regression analysis were performed to study the effect of 24 preoperative, 7 peroperative and 7 postoperative factors on the occurrence of 30-day postoperative worsening of renal function. RESULTS: Fifty-three patients had a 30-day postoperative decrease of renal function. Nine of these patients died, which is significantly more than the mortality without this complication (P<0.0001). In those nine patients, another complication (postoperative heart failure, thromboembolism or respiratory failure) was present. Thirteen factors were significant in an univariate analysis: preoperative renal dysfunction (P<0.001), age>80 (P<0.001), atrial fibrillation (P<0.001) , preoperative pulmonary edema (P=0.001), conduction defect (P=0.002), diabetes (P=0.006), myocardial infarction (P=0.006), postoperative heart failure (P=0.007), cross clamp time >75 min (P=0.015), previous coronary artery bypass grafting (CABG) (P=0.018), concomitant CABG (P=0.031), ejection fraction <50% (P=0.033) and CVA (P=0.035). Four factors were identified as independent predictors in a multivariate analysis: renal dysfunction (P<0.001, Odds ratio [OR] 5.5; 95% confidence interval [CI] 2.9-10.4), preoperative atrial fibrillation (P=0.010, OR=2.3, 95% CI=1.2-4.2), age>80 (P=0.014, OR=2.2, 95% CI=1.2-4.1) and myocardial infarction (P=0.022, OR=2.2, 95% CI=1.1-4.4). CONCLUSIONS: Few factors are liable for therapeutic intervention, especially in elderly and patients with comorbidity. In patients with risk factors, shortening of cross clamping time or installation of minimal extracorporeal circulation might be beneficial.

Determinants of survival after aortic valve replacement as treatment for symptomatic aortic valve disease in the elderly.

BACKGROUND AND AIM OF THE STUDY: The effect of concurrent disease and cardiac comorbidity on survival after bioprosthetic valve replacement in elderly patients was assessed retrospectively. Risk factors were categorized as general, non-cardiac (age, diabetes, previously treated carcinoma) and cardiac (LVEF, three-vessel disease, previous CABG or valve replacement, and endocarditis). METHODS: A total of 400 elderly patients (median age 73 years; range: 71-76 years) was studied. Medical history included diabetes, previous CABG or aortic valve replacement (AVR), endocarditis and treatment of previous carcinoma. A left ventricular ejection fraction (LVEF) of <0.66 and presence of three-vessel disease were also investigated. Hospital deaths (and cause) were recorded; survival or date and cause of death after discharge were obtained by questionnaire. Kaplan-Meier univariate and Cox proportional hazards multivariate regression analyses were carried out. RESULTS: Mortality during follow up was 28.3%; hospital mortality was 3.8%. Univariate analysis showed five factors significantly to affect survival: LVEF, history of endocarditis, carcinoma, age and three-vessel disease. Fifteen of 38 patients with history of carcinoma died, 10 due to a malignancy. Of 76 patients with three-vessel disease, 26 died. A history of diabetes and previous CABG did not influence survival significantly. Four of eight patients with preoperative endocarditis died, all in hospital. Six of 11 patients died after redo-AVR, none before 36 months follow up. By Cox regression analysis, LVEF and histories of carcinoma and endocarditis remained significant. CONCLUSION: AVR should be performed before ventricular deterioration occurs. Previous CABG is not a contraindication for AVR. Endocarditis impaired survival. Long-term mortality after redo-AVR in this population was relatively high, but acceptable. AVR should also be performed in elderly patients with aortic valve disease. Since prognosis of symptomatic aortic valve disease is poor in the short term, AVR is indicated in patients treated for carcinoma.

High-level transgene expression in primary human T lymphocytes and adult bone marrow CD34+ cells via electroporation-mediated gene delivery.

The design of effective gene delivery systems for gene transfer in primary human blood cells is important both for fundamental hematopoiesis research and for cancer gene therapy strategies. Here, we evaluated electroporation as a nonviral means for transfection of activated human T lymphocytes and adult bone marrow (BM) CD34+ cells. We describe optimal culture and electroporation parameters for efficient gene delivery in prestimulated T lymphocytes (16.3 +/-1.3%), as well as 2-day cultured adult BM CD34+ cells (29.6+/-4.6%). PHA-stimulated T cells were most receptive for transfection after 48h of in vitro culture, while T cells stimulated by CD3 cross-linking and interleukin (IL)-2 achieved maximum transfection levels after 72 h of prestimulation. Kinetic analysis of EGFP expression revealed that activated T lymphocytes maintained transgene expression at high levels for a prolonged period. In addition, fresh unstimulated BM CD34+ cells were consistently transfected (5.2+/-0.4%) with minimal cytotoxicity (<5%), even without preliminary CD34+ cell purification. Both T cells and CD34+ cells retained their phenotype and functional capacity after electroporation. These results demonstrate that electroporation is a suitable nonviral transfection technique that may serve applications in gene therapy protocols using T lymphocytes or CD34+ cells.

Developmentally regulated responsiveness to transforming growth factor-beta is correlated with functional differences between human adult and fetal primitive hematopoietic progenitor cells.

Important functional differences exist between primitive CD34++ CD38- hematopoietic progenitor cells derived from human fetal liver (FL) and adult bone marrow (ABM). FL progenitors are known to have higher proliferative capacities and lower cytokine requirements than their ABM counterparts. In this study, we isolated FL and ABM CD34++ CD38- cells and used a two-stage culture system to investigate the effects of transforming growth factor-beta (TGF-beta) and blocking anti-TGF-beta antibodies (anti-TGF-beta) on these cells. First, we demonstrate that FL progenitors are significantly less sensitive to the inhibitory effects of TGF-beta than ABM cells. Second, whereas ABM cells are significantly stimulated by anti-TGF-beta, only very limited effects are seen on FL cells. Third, we show that the effect of anti-TGF-beta is mainly situated at the level of the initial cell cycles of very primitive progenitor cells with a high proliferation potential. Fourth, we demonstrate that blocking the effects of endogenous TGF-beta reduces the growth factor requirements of ABM cells in order to proliferate and differentiate. Based on these data, we hypothesize that at least part of the functional differences that exist between adult and fetal stem cells can be accounted for by a developmental different responsiveness to TGF-beta.

Priming solutions for cardiopulmonary bypass: comparison of three colloids.

The present study was designed to compare the differences in the clinical effects of three colloidal solutions, albumin, urea-linked gelatin, and succinyl-linked gelatin, when used as priming fluids for cardiopulmonary bypass (CPB) under alpha-stat conditions. A consecutive series of 105 patients scheduled for cardiac surgery were randomized into three identically managed groups, except for the CPB prime. Variables relating to acid-base status, oncotic activity, metabolism, coagulation, and postoperative evaluation were measured. Marked differences in acid-base status, colloid osmotic pressure, additional prime requirements, blood lactate, urine output, and the need for buffer solutions occurred among groups, with the succinyl-linked gelatin group having better results than the other groups. Changes in hemodynamics, oxygen consumption, and blood-glucose levels during CPB did not vary among groups. There were also no important intergroup differences in hematologic and clotting variables or postoperative parameters such as blood loss or use of blood products. Electrolyte changes were similar except for a significant increase in ionized calcium that occurred in the urea-linked gelatin group after bypass. The results indicate that succinyl-linked gelatin is an adequate and safe alternative to human albumin for use as a colloid during CPB under alpha-stat conditions.

Predictive value of coagulation testing in cardiopulmonary bypass surgery.

Severe postoperative bleeding in cardiopulmonary bypass surgery is still a major problem. One hundred and seven patients undergoing uncomplicated coronary artery bypass grafting (CABG) were studied. Two groups were formed according to the patients' 24 hours postoperative mediastinal blood loss. Patients in group I (n = 70) had blood loss less than 1000 ml and patients in group II (n = 33) had blood loss over 1000 ml. Between the two groups, there were no differences in age, male-female ratio, number of grafts, by pass-time or heparin-protamine dose. Coagulation testing: APTT (Activated Partial Thromboplastin Time), PT (Prothrombin Time), fibrinogen, D-dim. (D-dimers), bleeding time, MPV (mean platelet volume) and platelet count, was done preoperatively (T0), immediately postoperatively (T1), 6 hours postoperatively (T2). We were especially interested in the predictive value of hemostatic parameters at T0 and T1. We found a slight but statistically negative correlation between the platelet count (T0 and T1) and the postoperative blood loss.

The cerebro-vascular problem in coronary by-pass surgery.

In 99 of 2250 consecutive C.B.P. cases, signs of cerebro-vascular disease (C.V.D.) were recorded in 87 (3.9%) on admission and in 12 post-operatively. The detection of C.V.D. by auscultation alone is very incomplete. There were 17 post-C.B.P. neurologic deficits (P.O.N.D.) (0.75%): 15 strokes (0.67%) and 2 T.I.A.'s. 26 patients (out of 87 detected on admission) were treated by carotid endarterectomy (C.E.) either pre-by-pass or simultaneously. There were no complications. The remaining 61 patients, who were not treated, had 4 strokes and 1 T.I.A. after their C.B.P. The most probable cause of these deficits was pre-existing C.V.D. Could more extensive pre-operative investigation, and treating the serious lesions by C.E., improve the P.O.N.D. incidence? The published series on simultaneous C.E. + C.B.P. are not yet conclusive. We favour C.E. done before the C.P.B. procedure except in very serious coronary disease when simultaneous operation is preferred.