Hans J. Geissler

Risk stratification in heart surgery: comparison of six score systems

OBJECTIVEnRisk 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.nnnMETHODSnBetween 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.nnnRESULTSnFollow-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.nnnCONCLUSIONSnAmong 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.

Myocardial fluid balance

Fluid accumulation in the cardiac interstitium or myocardial edema is a common manifestation of many clinical states. Specifically, cardiac surgery includes various interventions and pathophysiological conditions that cause or worsen myocardial edema including cardiopulmonary bypass and cardioplegic arrest. Myocardial edema should be a concern for clinicians as it has been demonstrated to produce cardiac dysfunction. This article will briefly discuss the factors governing myocardial fluid balance and review the evidence of myocardial edema in various pathological conditions. In particular, myocardial microvascular, interstitial, and lymphatic interactions relevant to the field of cardiac surgery will be emphasized.

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

OBJECTIVEnContinuous 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).nnnMETHODSnSixty 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.nnnRESULTSnThere 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).nnnCONCLUSIONnOur 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.

Cardioplegic arrest induces apoptosis signal-pathway in myocardial endothelial cells and cardiac myocytes

OBJECTIVEnMyocardial ischemia-reperfusion is associated with free radical-mediated injury and may be involved in cardiac apoptosis. The purpose of our study was to investigate (1) if cardioplegia-induced ischemia-reperfusion initiates cardiac apoptosis signal pathway, and (2) if this is mediated by free radicals.nnnMETHODSnWe subjected 13 pigs (56+/-10 kg) to 1 h of cold crystalloid cardioplegic arrest (CA) on cardiopulmonary bypass (CPB), and collected five transmural LV biopsies: prior to CPB (baseline), at 60 min CA, at 15 and 30 min reperfusion on CPB, and at 120 min post CPB. Two additional pigs were subjected to CPB but not CA and two further pigs were neither subjected to CPB nor CA and served as sham-operated time controls. LV specimens were cut at 7 microm and immunocytochemically stained against active caspase-3 and 85 kDa poly(ADP-ribose) polymerase (PARP) as apoptosis signal-pathway key enzymes, nitrotyrosine as indicator for peroxynitrite (ONOO(-))-mediated tissue injury, and 8-iso-prostaglandin-F(2)alpha as indicator for oxygen free radical-mediated lipid peroxidation. Specimen were assessed using a scale of 0 (negative) to 3 (highly positive), and cardiomyocytes were quantitatively investigated using TV densitometry.nnnRESULTSnAt 60 min CA, caspase-3 was increased by 9.2+/-3.7 gray units and remained on this level until 2 h post CPB (P</=0.003 vs. baseline); nitrotyrosine increased over time to reach a maximum of +8.5+/-8.1 gray units at 120 min post CPB (P=0.016); and there was a trend for increased 8-iso-prostaglandin-F(2)alpha at 60 min CA (+3.6+/-4.7 gray units; P=0.089). At 60 min CA, 92% of the hearts showed active caspase-3, only 42% demonstrated nitrotyrosine formation, and 58% exhibited 8-iso-prostaglandin-F(2)alpha. At 120 min post CPB, most hearts positive for caspase-3 were also positive for nitrotyrosine (83%), and 8-iso-prostaglandin-F(2)alpha (75%), but no heart showed PARP cleavage. Hearts subjected to CPB but not CA as well as time controls remained negative for all variables.nnnCONCLUSIONSnOur data show that CA initiates apoptosis signal-pathway in myocardial endothelium and myocytes; however, this did not result in apoptotic cell death as we did not find PARP cleavage. Further, the data suggest that CA-induced apoptosis signal pathway activation is not mediated by free radicals as caspase-3 activation preceded both nitrotyrosine and 8-iso-prostaglandin-F(2)alpha formation.

Effects of Myocardial Edema on the Development of Myocardial Interstitial Fibrosis

Objective: The mechanism by which chronic myocardial edema causes cardiac dysfunction is poorly understood. We hypothesized that myocardial edema triggers cardiac fibrosis development resulting in cardiac dysfunction. Since collagen is the most abundant constituent of the interstitial matrix, we examined the effects of edema development on cardiac collagen metabolism.

Loss of β1D-integrin function in human ischemic cardiomyopathy

AbstractIntegrins play a pivotal role in cardiomyocyte survival andnfunction, with integrin loss leading to myocyte apoptosis and heart failure.nThe aim of this study was to characterize whether regulation of integrinsnmay contribute to cardiac remodeling in human ischemic cardiomyopathyn(ICM).Myocardial tissues of the left ventricle were obtained from patientsnwith ICM (n = 8) undergoing cardiac transplantation and from unusedndonor hearts (NF, n = 8). In addition, tissue samples from patients with dilatedncardiomyopathy (DCM, n = 5) were analyzed. Expression of integrinsnβ1D and β3, the effector proteins focal adhesion kinase (FAK) and melusin,nand FAK phosphorylation were examined by Western blotting, real-time-PCR and immunofluorescence analysis, respectively. β1D-integrin proteinnwas decreased in ICM vs. NF by 36%. β1D-integrin mRNA levels and β1D-integrinnshedding were unchanged. Corresponding to β1D-integrin regulation,nFAK and phosphorylated FAK were decreased in ICM vs. NF by 54%nand 49%, respectively. β3-integrin and melusin were not altered in ICM. Asna mediator of integrin effects, AKT kinase activity was examined. In parallelnto β1D-integrin and FAK, AKT activity was decreased in ICM by 44%. Inncontrast, none of the proteins were significantly altered in DCM comparednto NF.Integrins and integrin signaling are regulated differentially in ICM andnDCM with a decrease of β1D-integrin and FAK in ICM. The loss of the β1Dintegrin-FAK-complex in ICM was paralleled by a reduced AKT activity supportingnin vitro data which demonstrate the pivotal role of intact integrinnfunction in anti-apoptotic signaling and cell survival.

Morphological and Quantitative Changes of the Initial Myocardial Lymphatics in Terminal Heart Failure

BACKGROUNDnTerminal heart failure is associated with chronic myocardial edema, which in part is compensated by increased myocardial lymph flow. However, little is known about the impact of terminal heart failure on lymphangiogenesis. The purpose of the study was to investigate the morphological and quantitative changes of the initial myocardial lymphatics in terminal heart failure.nnnMETHODSnParaffin-embedded left ventricular endomyocardial biopsies, taken during heart transplantation from 7 heart transplant recipients (failing heart) and 8 heart transplant donors (control), were investigated by immunohistostaining and triple immunofluorescence for lymphatic endothelial markers LYVE-1, PROX-1, and VEGFR-3. The vessel density was calculated and the ratio of open versus collapsed vessels was estimated by analyzing randomly selected marked vessels.nnnRESULTSnThe absolute densities of lymph vessels in failing and control myocardium were not significantly different for all investigated markers. The ratio of open LYVE-1 positive lymph vessels in failing heart was significantly higher than in control (64+/-12.5 vs. 44.3+/-9.3, p<0.008). There was no difference for the ratio of open VEGFR-3 vessels between groups (69.0+/-17.5 vs. 70.7+/-17.2). Triple fluorescent immunohistostaining revealed in failing hearts LYVE-1 and PROX-1 positive open vessels, which were VEGFR-3 negative. VEGFR-3 positive, but LYVE-1 and PROX-1 negative vessels could also be seen.nnnCONCLUSIONSnMyocardial initial lymphatics in patients with terminal heart failure undergo significant morphological changes in comparison to normal hearts. The ratio of open LYVE-1 vessels was higher in failing hearts by no difference in absolute densities for all markers. These findings suggest that appositional growth of initial lymphatics, rather than de novo genesis from pluripotent stem cells or sprouting from preexisting venous vessels, may be the predominant mechanism of lymphangiogenesis in terminal heart failure.

Cold crystalloid cardioplegia

Cold crystalloid cardioplegia is clinically used since the mid-1960s. It is currently applied in adult and pediatric cardiac surgery patients and remains the preferred method of myocardial protection for many cardiac surgeons. This chapter gives a brief overview about the technical aspects of cold crystalloid cardioplegia application in the operating room.

The heavily calcified aorta and re-do CABG surgery: technical considerations how to avoid aortic crossclamp. How-to-do-it.

Aortic crossclamp may increase the risk for acute aortic dissection and embolic stroke in patients with severe aortic calcification. Additionally, in CABG re-operation aortic crossclamp may necessitate extensive dissection of fibrous adhesions which may intensify the potential risk of injury to the aorta, pulmonary artery or patent bypass grafts. Therefore, it appears to be advantageous in patients undergoing re-do CABG or with aortic calcification to minimize surgical manipulation of the aorta by abandonment of aortic crossclamp. Adequate myocardial protection and convenient surgical exposure without aortic crossclamp max be achieved by intraaortic administration of the short acting ss-blocker esmolol.

Loss of β 1 D-integrin function in humanischemic cardiomyopathy

AbstractIntegrins play a pivotal role in cardiomyocyte survival andnfunction, with integrin loss leading to myocyte apoptosis and heart failure.nThe aim of this study was to characterize whether regulation of integrinsnmay contribute to cardiac remodeling in human ischemic cardiomyopathyn(ICM).Myocardial tissues of the left ventricle were obtained from patientsnwith ICM (n = 8) undergoing cardiac transplantation and from unusedndonor hearts (NF, n = 8). In addition, tissue samples from patients with dilatedncardiomyopathy (DCM, n = 5) were analyzed. Expression of integrinsnβ1D and β3, the effector proteins focal adhesion kinase (FAK) and melusin,nand FAK phosphorylation were examined by Western blotting, real-time-PCR and immunofluorescence analysis, respectively. β1D-integrin proteinnwas decreased in ICM vs. NF by 36%. β1D-integrin mRNA levels and β1D-integrinnshedding were unchanged. Corresponding to β1D-integrin regulation,nFAK and phosphorylated FAK were decreased in ICM vs. NF by 54%nand 49%, respectively. β3-integrin and melusin were not altered in ICM. Asna mediator of integrin effects, AKT kinase activity was examined. In parallelnto β1D-integrin and FAK, AKT activity was decreased in ICM by 44%. Inncontrast, none of the proteins were significantly altered in DCM comparednto NF.Integrins and integrin signaling are regulated differentially in ICM andnDCM with a decrease of β1D-integrin and FAK in ICM. The loss of the β1Dintegrin-FAK-complex in ICM was paralleled by a reduced AKT activity supportingnin vitro data which demonstrate the pivotal role of intact integrinnfunction in anti-apoptotic signaling and cell survival.