Ferdinand Kuhn-Régnier

Risk stratification in heart surgery: comparison of six score systems

OBJECTIVE Risk scores have become an important tool in patient assessment, as age, severity of heart disease, and comorbidity in patients undergoing heart surgery have considerably increased. Various risk scores have been developed to predict mortality after heart surgery. However, there are significant differences between scores with regard to score design and the initial patient population on which score development was based. It was the purpose of our study to compare six commonly used risk scores with regard to their validity in our patient population. METHODS Between September 1, 1998 and February 28, 1999, all adult patients undergoing heart surgery with cardiopulmonary bypass in our institution were preoperatively scored using the initial Parsonnet, Cleveland Clinic, French, Euro, Pons, and Ontario Province Risk (OPR) scores. Postoperatively, we registered 30-day mortality, use of mechanical assist devices, renal failure requiring hemodialysis or hemofiltration, stroke, myocardial infarction, and duration of ventilation and intensive care stay. Score validity was assessed by calculating the area under the ROC curve. Odds ratios were calculated to investigate the predictive relevance of risk factors. RESULTS Follow-up was able to be completed in 504 prospectively scored patients. Receiver operating characteristics (ROC) curve analysis for mortality showed the best predictive value for the Euro score. Predictive values for morbidity were considerably lower than predictive values for mortality in all of the investigated score systems. For most risk factors, odds ratios for mortality were substantially different from ratios for morbidity. CONCLUSIONS Among the investigated scores, the Euro score yielded the highest predictive value in our patient population. For most risk factors, predictive values for morbidity were substantially different from predictive values for mortality. Therefore, development of specific morbidity risk scores may improve prediction of outcome and hospital cost. Due to the heterogeneity of morbidity events, future score systems may have to generate separate predictions for mortality and major morbidity events.

Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria.

OBJECTIVES To elucidate the structural basis for the electrophysiologic remodeling induced by chronic atrial fibrillation (AF), we investigated connexin40 and connexin43 (Cx40 and Cx43) expression and distribution in atria of patients with and without chronic AF and in an animal model of AF with additional electrophysiologic investigation of anisotropy (ratio of longitudinal and transverse velocities). BACKGROUND Atrial fibrillation is a common arrhythmia that has a tendency to become persistent. Since gap junctions provide the syncytial properties of the atrium, changes in expression and distribution of intercellular connections may accompany the chronification of AF. METHODS Atrial tissues isolated from 12 patients in normal sinus rhythm at the time of cardiac surgery and from 12 patients with chronic AF were processed for immunohistology and immunoblotting for the detection of the gap junction proteins. The functional study of the cardiac tissue anisotropy was performed in rat atria in which AF was induced by 24 h of rapid pacing (10 Hz). RESULTS Immunoblotting revealed that AF did not induce any significant change in Cx43 content in human atria. In contrast, a 2.7-fold increase in expression of Cx40 was observed in AF. Immunohistologic analysis indicated that AF resulted in an increase in the immunostaining of both connexins at the lateral membrane of human atrial cells. A similar spatial redistribution of the Cx43 signal was seen in isolated rat atria with experimentally-induced AF. In addition, AF in rat atria resulted in decreased anisotropy with slightly enhanced transverse conduction velocity. CONCLUSIONS This experimental study showed that AF is accompanied by spatial remodeling of gap junctions that might induce changes in the biophysical properties of the tissue.

Evidence for Functional Relevance of an Enhanced Expression of the Na+-Ca2+ Exchanger in Failing Human Myocardium

BACKGROUND The present study aimed at investigating the expression of the Na(+)-Ca2+ exchanger and its functional role in human failing myocardium. METHODS AND RESULTS Na(+)-Ca2+ exchanger mRNA and protein levels were examined in nonfailing (NF, n = 8) and failing human myocardium (New York Heart Association functional class IV) with idiopathic dilated cardiomyopathy (DCM, n = 8) or ischemic heart disease (ICM, n = 6). The inotropic effect of the Na+ channel activator BDF 9148 was determined in electrically driven left ventricular papillary muscle strip preparations (1 Hz, 37 degrees C) from nonfailing (n = 8) and failing (n = 8) human hearts. Na(+)-Ca2+ exchanger mRNA levels were significantly increased, by 79% (P < .001) in DCM and by 58% (P < .01) in ICM compared with NF; protein levels increased by 36% (P < .001) and by 20% (P < .05), respectively. BDF 9148 increased the force of contraction concentration dependently, with a similar maximal effect in NYHA class IV and NF, but was more potent in NYHA class IV as demonstrated by a significantly smaller (P < .01) EC50 value (NYHA class IV, 0.18 [0.16 to 0.22] mumol/L; NF, 1.65 [1.3 to 3.0] mumol/L). In NYHA class IV, BDF 9148 (0.1 mumol/L) restored the positive force-frequency relationship and reduced the frequency-dependent increase in diastolic tension in relation to force of contraction. CONCLUSIONS The increased expression of the Na(+)-Ca2+ exchanger is a possible explanation for the increased inotropic potency of the Na+ channel activator BDF 9148 in failing human myocardium. The increase in exchanger molecules could be of functional relevance for the modulation of cardiac contractility by agents that increase the intracellular Na+ concentration. Enhancement of Na(+)-Ca2+ exchanger activity might be a powerful mechanism for increasing cardiac contractility in chronic heart failure.

Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.

OBJECTIVE Continuous perfusion of the coronary arteries with beta-blocker (esmolol)-enriched normothermic blood during cardiac surgery has been suggested as an alternative technique for myocardial protection. The aim of the present study was to compare the beta-blocker technique to Buckbergs blood cardioplegia during coronary artery bypass grafting (CABG). METHODS Sixty patients with coronary artery disease were randomly assigned to either the esmolol group (ES, n = 30) or the blood cardioplegia group (BC, n = 30). During aortic crossclamp ES patients received continuous normothermic coronary perfusion with esmolol-enriched blood. Hearts of the BC group were protected by antegrade cold blood cardioplegia according to Buckberg. We measured left ventricular (LV) contractility using TEE (fractional area of contraction, FAC) and hemodynamic parameters prior to cannulation for cardiopulmonary bypass (CPB), after decannulation, and 4 h postoperatively. Myocardial lactate release was measured prior to aortic cross-clamp, during cross-clamp, and after decannulation. LV biopsies for determination of heat-shock protein (HSP-70), actin pattern and intercellular adhesion-molecule (ICAM-I) as indicators for structural changes were collected prior CPB, at the end of the aortic cross-clamp period, and prior to weaning off CPB. RESULTS There was no significant difference between both groups with respect to grafts and cross-clamp time. ES hearts did not release lactate during cross-clamp. In contrast, BC hearts released significant amounts of lactate. Post CPB FAC and hemodynamics under similar inotropic stimulation showed no difference between groups, whereas at 4 h post CPB measurements showed slightly better values in the ES group: cardiac index: ES: 2.9+/-0.1 (SEM) versus BC: 2.6+/-0.1 L/min per m2 (P < 0.05); FAC: ES: 55+/-3 versus BC: 48+/-3% (P < 0.05). HSP-70 and actin pattern showed no difference between groups; however, ICAM-I showed a significantly higher degree of structural changes in BC hearts: 18+/-2 versus ES: 11+/-1% (P < 0.05). CONCLUSION Our data demonstrate that application of the beta-blocker technique during routine CABG was associated with slightly better functional recovery and less structural myocardial alteration as compared with intermittent cold blood cardioplegia, however, both techniques provided equivalent myocardial protection in terms of patient outcome. Future studies are required to investigate if myocardial ischemia minimization by use of the beta-blocker technique may be beneficial in compromized hearts.

Coronary oxygen persufflation combined with HTK cardioplegia prolongs the preservation time in heart transplantation.

BACKGROUND One of the most restricting factors remaining in heart transplantation is the limited myocardial ischemia time. A new approach towards the prolongation of this time is the combination of primary cardioplegic arrest followed by continuous coronary oxygen persufflation (COP) with gaseous oxygen. METHODS This technique was applied in pig hearts, which we transplanted orthotopically after cardioplegic arrest by original (n = 5) and modified (addition of hyaluronidase: n = 11) Bretschneider HTK solution and 14 h of hypothermic preservation. Depending on the different preservation techniques, we created four groups: (1), original HTK (HTK), n = 5; (2), modified HTK (mHTK), n = 5; (3), modified HTK solution plus COP (mHTK + COP), n = 6; and (4), as a control five hearts were transplanted after cardioplegic arrest by the original HTK solution and a cold ischemia time of 3 h comparable to clinical routine procedure. RESULTS After 14 h of preservation and orthotopic transplantation, cardiac functional recovery in mHTK + COP hearts was similar to control hearts, and improved compared to hearts of both other groups. Hemodynamics were significantly better in hearts preserved by mHTK + COP and in the control group compared to the HTK-hearts (P < 0.05), not significant compared to mHTK hearts (dp/dt(max) in % of preoperative +/- standard error of mean (SEM): mHTK + COP, 85 +/- 9; control, 85 +/- 10.5; mHTK, 59 +/- 14; HTK, 50 +/- 4). The cardiac output (CO) in % of preoperative was: mHTK + COP, 68 +/- 5.4; control, 64 +/- 4; mHTK, 44 +/- 2.7; HTK, 25 +/- 11. The ATP of left ventricular myocardium in mHTK + COP hearts at 14.7 +/- 1 micromol/g dry weight (DW) and in the control at 14.59 +/- 1.8 was higher compared to that in mHTK at 12.2 +/- 2.8 (P is non-significant (n.s.) versus mHTK + COP and control) and in HTK-hearts at 7.0 +/- 0.5 (P < 0.05 versus mHTK + COP and control). CK-MB in percent of CK showed no increase in either group. CONCLUSIONS These data show that COP combined with a mHTK solution represents a potential alternative to complement currently used cold storage techniques for prolonged preservation periods.

Evidence against a role of nitric oxide in the indirect negative inotropic-effect of M-cholinoceptor stimulation in human ventricular myocardium

Nitric oxide (NO) has been reported to mediate several effects in response to muscarinic cholinergic stimulation in cardiovascular tissues. Recently, an attenuation of guinea pig cardiac myocyte contraction by NO has been described. The aim of the present study was to determine whether the indirect negative inotropic effect of M-cholinoceptor stimulation in human myocardium is in part due to an effect of endogenous NO. Therefore, the effect of carbachol was studied under control conditions and during inhibition of NO-synthase by pretreatment with NG-monomethyl-l-arginine (NMMA). Functional experiments were performed in isolated, electrically driven (1 Hz, 37°C) left ventricular papillary muscle strips of human myocardium. Since cytokines have been reported to be increased in the serum of patients with heart failure and could induce NO-synthase activity in failing myocardium, we compared samples from nonfailing and terminally failing (classified as NYHA IV) hearts. The indirect negative inotropic effect of carbachol (10 μmol/l) was studied in the presence of the \-adrenoceptor agonist isoprenaline (0.03 μmol/l).After stimulation with isoprenaline, carbachol significantly (P < 0.05) reduced force of contraction. This effect was diminished in failing myocardium compared to nonfailing, probably due to the diminished inotropic response most likely due to the lower cAMP levels in response to \-adrenoceptor stimulation in the former condition. Pretreatment with NMMA (100 μmol/l) altered the antiadrenergic effect of carbachol neither in nonfailing nor in failing preparations. Furthermore, inhibition of guanylyl cyclase, the target enzyme of NO, by preincubation with methylene blue (10 μmol/l) for 30 min had no effect on the carbachol-induced decrease in force of contraction. Basal force of contraction, as well as the positive inotropic effect of isoprenaline remained unaffected by NMMA or methylene blue.The present study provides evidence that the indirect negative inotropic effect of M-cholinoceptor agonists is not due to an effect of NO in the human myocardium. Furthermore, the well known enhancement of cGMP in response to M-cholinoceptor stimulation appears not to be involved in this antiadrenergic effect.

Total recovery of heart grafts of non–heart-beating donors after 3 hours of hypothermic coronary oxygen persufflation preservation in an orthotopic pig transplantation model12

Background. The coronary oxygen persufflation (COP) technique has been previously shown to allow prolonged heart preservation of 14 hr with optimal recovery in a pig model of orthotopic transplantation. This technique may be applicable to hearts grafted from non–heart-beating donors (NHBD). Methods. Experiments were performed on pigs to test the effectiveness of oxygenated preservation, using COP for preservation of NHBD hearts. After 16 min of in situ normothermic ischemia, the hearts were flushed with histidine-tryptophan-ketoglutarate (HTK) solution or modified HTK solution (mBHTK) including 30 mmol/L 2,3-butanedione monoxime, 40 mg/L hyaluronidase,15 &mgr;mol/L adenosine, and 50 &mgr;mol/L calcium. Hearts were stored in the flush solutions for 3.3 hr or additionally persufflated with gaseous oxygen through the coronary arteries (COP) and transplanted orthotopically. Results. Simple storage in HTK did not allow recovery of these hearts, whereas mBHTK storage resulted in improved function with 1.1 L/min cardiac output. The cardiac output reached 2.8 L/min (68% of normal values) with a left ventricular developed pressure of 101 mm Hg only after mBHTK+COP. Then the hearts were able to guarantee the circulation of the recipient for the test period after weaning from the heart-lung machine. Conclusions. Even in an NHBD with more than 15 min of in situ ischemia, the use of COP in combination with mBHTK solution for 3.3-hr storage of the heart allows excellent recovery of transplanted hearts and normal weaning from the heart-lung machine. This indicates that COP combined with mBHTK may be an optimal preservation technique for use with NHBD hearts.

Megakaryocytes and fibroblasts—Interactions as determined in normal human bone marrow specimens

An in vitro study was performed to investigate possible interactions between megakaryocytes and bone marrow fibroblasts, both obtained from healthy donors. We were able to demonstrate that the proliferation of fibroblasts increased significantly by co-culturing these cells with megakaryocytes for 6 days. Addition of neutralizing antibodies for PDGF and TGF beta 1, caused a significant reduction of fibroblast growth. Inhibition of cell to cell contacts via tissue culture inserts generated a conspicuous impairment of fibroblast proliferation compared with megakaryocyte-fibroblast co-cultures, where contact was allowed. Hence, our findings suggest that a close spatial relationship between megakaryocytes and fibroblasts is needed for the activation of growth in normal human bone marrow. Neighbouring of megakaryocytes and fibroblasts seems to be necessary in order to achieve a certain threshold of local growth factor concentration. Our results are in keeping with the assumption that PDGF and TGF beta 1, are secreted by normal human megakaryocytes in very low concentrations and promote significantly fibroblast proliferation.

Echinococcus cyst located in the interventricular septum

Michael Gerharz Institute of Pathology University of Cologne Cologne, Germany Sirs: Hydatid disease is a zoonosis that is caused by Echinococcus granulosus. The parasites reside mostly in the liver, sometimes in the lung. It transforms into a cyst and may stay latent for many years [3, 28]. Cardiac manifestations are rare and occur in about 0.2 to 3% of all cases of human hydatidosis. Predominant location in the heart is the left ventricle (75%) followed by the right ventricle (18%) and the interventricular septum (7%) [30]. We report an isolated hydatid cyst of the interventricular septum without hepatic or lung manifestations that caused obstruction of the right ventricular outflow tract. Case report

Impact of gender on long-term outcomes after surgical repair for acute Stanford A aortic dissection: a propensity score matched analysis†

OBJECTIVES Previous research suggests that female gender is associated with increased mortality rates after surgery for Stanford A acute aortic dissection (AAD). However, women with AAD usually present with different clinical symptoms that may bias outcomes. Moreover, there is a lack of long-term results regarding overall mortality and freedom from major cerebrovascular events. We analysed the impact of gender on long-term outcomes after surgery for Stanford A AAD by comparing genders with similar risk profiles using propensity score matching. METHODS A total of 240 patients operated for Stanford A AAD were included in this study. To control for selection bias and other confounders, propensity score matching was applied to gender groups. RESULTS After propensity score matching, the gender groups were well balanced in terms of risk profiles. There were no statistically significant differences regarding duration of cardiopulmonary bypass ( P  = 0.165) and duration of aortic cross-clamp time ( P  = 0.111). Female patients received less fresh frozen plasma ( P  = 0.021), had shorter stays in the intensive care unit ( P  = 0.031), lower incidence of temporary neurological dysfunction ( P  < 0.001) and lower incidence of dialysis ( P  = 0.008). There were no significant differences regarding intraoperative mortality ( P  = 1.000), 30-day mortality ( P  = 0.271), long-term overall cumulative survival ( P  = 0.954) and long-term freedom from cerebrovascular events ( P  = 0.235) with up to a 9-year follow-up. CONCLUSIONS Considering patients with similar risk profiles, female gender per se is not associated with worse long-term survival and freedom from stroke after surgical aortic repair. Moreover, female patients might even benefit from a smoother early postoperative course and lower incidence of early postoperative complications.OBJECTIVES Previous research suggests that female gender is associated with increased mortality rates after surgery for Stanford A acute aortic dissection (AAD). However, women with AAD usually present with different clinical symptoms that may bias outcomes. Moreover, there is a lack of long-term results regarding overall mortality and freedom from major cerebrovascular events. We analysed the impact of gender on long-term outcomes after surgery for Stanford A AAD by comparing genders with similar risk profiles using propensity score matching. METHODS A total of 240 patients operated for Stanford A AAD were included in this study. To control for selection bias and other confounders, propensity score matching was applied to gender groups. RESULTS After propensity score matching, the gender groups were well balanced in terms of risk profiles. There were no statistically significant differences regarding duration of cardiopulmonary bypass (P = 0.165) and duration of aortic cross-clamp time (P = 0.111). Female patients received less fresh frozen plasma (P = 0.021), had shorter stays in the intensive care unit (P = 0.031), lower incidence of temporary neurological dysfunction (P < 0.001) and lower incidence of dialysis (P = 0.008). There were no significant differences regarding intraoperative mortality (P = 1.000), 30-day mortality (P = 0.271), long-term overall cumulative survival (P = 0.954) and long-term freedom from cerebrovascular events (P = 0.235) with up to a 9-year follow-up. CONCLUSIONS Considering patients with similar risk profiles, female gender per se is not associated with worse long-term survival and freedom from stroke after surgical aortic repair. Moreover, female patients might even benefit from a smoother early postoperative course and lower incidence of early postoperative complications.