Immunohistochemical study of remodeling of myocardial lymphatic and blood microvascular structures in terminal heart failure: differences between ischemic and dilated cardiomyopathy.

This study investigated (cardiac) remodeling of the myocardial microvasculature in patients with terminal heart failure due to ischemic (ICM) and dilative (DCM) cardiomyopathy. Seventeen transmural left-ventricular (LV) biopsies (9 ICM and 8 DCM), taken from heart transplant recipients at transplantation (n=4) or during ventricular assist device implantation (n=13) were investigated by immunohistostaining for VEGFR-1 and VEGFR-2 as capillary markers and VEGFR-3, D2-40, PROX-1 and LYVE-1 as lymphatic markers. Results were compared to LV biopsies from 7 donor hearts (control). Compared to control, DCM hearts showed a significantly higher density of LYVE-1 positive lymphatics (p < 0.05), whereas no difference was seen for other markers. ICM hearts showed a significantly higher density of D2-40 positive lymphatics (p < 0.01) and a lower density of VEGFR-2 capillaries compared to control (p < 0.05). In comparison to normal donor hearts, ICM and DCM hearts showed a significantly different pattern of microvascular receptor expression. As distinct patterns were seen in ICM and DCM, the effect of microvascular remodeling may be substantially different between two clinically important causes of cardiomyopathy. Further research should be aimed at defining the impact of extracellular matrix composition and VEGF-related angiogenesis on the myocardial microvasculature at various stages of heart failure.

In-vivo measurements of coronary blood flow using 16-slice multidetector spiral computed tomography (MDCT) in a porcine model.

PURPOSE: To determine whether CTCA supplemented with CT flow measurements can be used to demonstrate and semiquantitatively evaluate poststenotic coronary blood flow in a porcine model. MATERIALS AND METHODS: In 10 thoracotomized pigs, transit time flow meter probes were attached to the aorta and left anterior descending artery (LAD) for real-time blood flow volumetry. A vascular silicone occluder was deployed around the LAD proximal to the probe to create medium-grade (MGS) and high-grade stenoses (HGS). The blood flow was measured by CT without vessel occlusion and distal to the stenoses. Time-density curves were generated from CT data. The curves were evaluated by calculating and cross-plotting the variables "slope of the density increase", "peak density" and "slope of the post-peak density decrease" from the LAD and aortic CT data. RESULTS: The flow in the LAD dropped to 41 % +/- 9 % (mean +/- SD) for MGS and 12 % +/- 6 % for HGS of the baseline. Coronary time-density curves plateaued proportional to luminal narrowing. Unimpaired flow could be differentiated statistically significant from poststenotic flow adjacent to MGS and HGS (p < 0.000 and p < 0.002, respectively). Flow adjacent to MGS and HGS was successfully differentiated for "slope of the density increase" and "slope of the post-peak density decrease" (p < 0.003 and p < 0.030, respectively). CONCLUSION: CT measurements allow semiquantitative evaluation of poststenotic coronary blood flow.

[Minimum provider volumes in heart surgery]. / Erfahrungen mit Mindestmengen in der Herzchirurgie.

The introduction of minimum provider volumes for certain medical procedures has been the subject of scientific investigation and political controversy for quite a while. The core of the discussion focuses on the hypothesis that minimum provider volumes could significantly improve operative results and cost efficiency. In Germany the Fifth Volume of Social Law (Sozialgesetzbuch V) set the legal stage for the implementation of minimum provider volumes. This article is a brief review on the experience with minimum provider volumes in cardiac surgery. The main focus is on coronary artery bypass surgery, as this happens to be the most frequently investigated procedure.

Risk stratification models fail to predict hospital costs of cardiac surgery patients.

BACKGROUND: The aim of this prospective study was to determine if commonly used risk stratification models can predict total hospital costs in cardiac surgical patients. METHODS: Between October 1st and December 31st 2003, all consecutive adult patients undergoing cardiac surgery on CPB at our institution were classified using seven risk stratification scoring systems: EuroSCORE, Cleveland, Parsonnet, Ontario, French, Pons, and CABDEAL. Total hospital costs for each patient were calculated on a daily basis including preoperative diagnostic tests, operating room costs, disposable materials, drugs, blood components, costs for personnel, and hospital fixed-costs. Linear regression analysis was used to determine the correlation between costs and the seven risk stratifications models as well as length of stay (LOS) on ICU. The Spearman correlation coefficient was calculated from the regression line, and an analysis of residuals was performed to determine the quality of the regression. RESULTS: A total of 252 patients were operated for CABG (n=175), valve (n=39), CABG plus valve (n=21), thoracic aorta (n=13) and miscellaneous (2 myxoma, 1 ASD, 1 pulmonary embolism). Mean age of the patients was 66.0+/-11.4 years, 29.4% were female. LOS on ICU was 3.3+/-6.3 days and the 30-day mortality rate was 6.7%. Spearman correlation between the seven risk stratification models and hospital costs was below r=0.32 (p=0.0001), but was r=0.94 (p=0.0001) between ICU LOS and costs. CONCLUSIONS: Total hospital costs can be identified by length of ICU stay. None of the common risk stratification models accurately predicted total hospital costs in cardiac surgical patients.

VDD-pacemaker in children--a long-term therapy?

AIMS: Transvenous AV-synchronous pacing in children started with the invention of smaller sized VDD leads and miniaturization of pacemakers. Whether or not this is a favourable long-term therapy was retrospectively investigated by us based on data from our records. METHODS: From May 1977 to July 2001 we implanted pacemakers in 104 children younger than 15 years of age. In 55 patients transvenous leads were implanted. Twelve of these (21.8 %) received a VDD pacemaker for hemodynamic reasons. RESULTS: Ages ranged from 11 months to 14.5 years (mean 7.7 +/- 4.3 y). Sizes of the children ranged from 67 to 141 cm (mean 105.9 +/- 15.5 cm) and body weight ranged from 5.3 to 62.0 kg (mean 22.5 +/- 9.8 kg). The mean follow-up period was 47.5 +/- 15.1 months. In 86.3 % of the time during follow-up pacemakers of which we obtained data were working in the VDD mode. Five of the twelve VDD patients (41.7 %) had to be reoperated because of severe traction on the leads. In all five patients the VDD systems were explanted and the patients changed to dual chamber pacemakers. The period of time between implantation and VDD lead explantation ranged from 24 to 74 months (48.6 +/- 18.5). CONCLUSIONS: VDD pacemakers can be implanted safely even in children with a low complication rate perioperatively. 41.7 % of our VDD patients had to be reoperated within the surveillance time because of severe lead tension due to thoracic growth. In our experience VDD pacemakers in smaller children seem to be a temporary solution to bridge AV-synchrony from a young age to DDD pacing in young adulthood.

The effect of preoperative antiplatelet therapy in coronary artery surgery: blood transfusion requirements for patients on cardiopulmonary bypass.

INTRODUCTION: Bleeding after heart operations remains a common complication and contributes to morbidity and death. Recent studies have suggested that antiplatelet therapy (APT) may not increase homologous blood requirements in coronary bypass surgery. The purpose of this study was to examine the influence of APT therapy on haemorrhage and transfusion requirements in patients undergoing coronary artery bypass (CABG) on cardiopulmonary bypass (CPB). MATERIALS AND METHODS: Records from 290 consecutive patients who underwent CABG with CPB were retrospectively reviewed, including 145 patients who received APT within 5 days prior to surgery and 145 control patients (CON). Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge. RESULTS: Both groups were well matched with respect to demographic and intra-operative data. There was significantly (p < 0.0005) more mediastinal tube drainage at 24 h in the APT group (1123 mL +/- 537 mL) compared to CON patients (874 mL +/- 351 mL). In addition, the APT group received significantly more units of blood (APT: 2.6 +/- 2.5 vs CON: 1.6 +/- 1.8; p < 0.0005), platelet units (APT: 1.2 +/- 1.8 vs CON: 0.2 +/- 0.8; p < 0.0005), and fresh frozen plasma units (APT: 2.0 +/- 2.2 vs CON: 1.3 +/- 2.0; p = 0.01). CONCLUSION: This study suggests consideration should be given to delaying elective CABG for patients who have received APT treatment until APT is discontinued for at least 5 days.

Impact of tranexamic acid vs. aprotinin on blood loss and transfusion requirements after cardiopulmonary bypass: a prospective, randomised, double-blind trial.

INTRODUCTION: Aprotinin (AP) reduces blood loss and transfusions after cardiopulmonary bypass (CPB), but may sensitise patients and is expensive. Tranexamic acid (TA) has less side-effects, but data regarding its efficacy are controversial. The aim of our prospective, randomised, double-blind study was to compare the impact of AP vs. TA on drainage blood loss and transfusion requirements in patients undergoing first time CABG on CPB. MATERIALS AND METHODS: One hundred and twenty adult patients were randomised to receive either high-dose AP according to Hammersmith or a total of 2 g TA. Perioperative blood products were transfused in a standardised fashion. Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge. RESULTS: The data from 118 patients (TA: n = 58, AP: n = 60) who completed the study according to protocol were analysed. Blood loss at 24 h postoperation in TA patients was significantly higher (896 +/- 354 ml) as compared to AP patients (756 +/- 347 ml; p = 0.03). TA patients received 1.5 +/- 1.5 units of red blood cells (AP: 1.5 +/- 1.7, p = 1.0), 1.3 +/- 2.0 units of fresh frozen plasma (AP: 1.0 +/- 2.0, p = 0.38) and 0.5 +/- 1.4 units of platelets (AP: 0.2 +/- 0.7, p = 0.15). Clinical data, including perioperative myocardial infarction rate, acute renal failure, mechanical ventilation, hospital stay and mortality, were not significantly different between either group. CONCLUSION: Our data show a difference in blood loss between TA and high-dose AP. Although statistically significant, it has little clinical relevance, because perioperative transfusion requirements were similar for both groups. Thus, TA appears to be a cost-effective alternative to AP in primary CABG patients.

Morphology and density of initial lymphatics in human myocardium determined by immunohistochemistry.

BACKGROUND: Myocardial edema is a common finding in congestive heart failure, transplant rejection, and cardiomyopathy. Although pathological alterations in the lymphatic morphology are part of the underlying disease, knowledge on these changes is limited. However, lymphatic morphology may be investigated by immunohistochemical staining for fms-like tyrosine 4 kinase (flt-4), which is specific for lymphatic endothelium in adult tissue. METHODS: We used myocardial tissue of ventricular out flow tract taken from five human semilunar valves harvested as allografts but unsuitable for implantation for analysis, performing immunohistochemical staining for flt-4 with a commercially available antibody. Lymphatic morphometry was completed according Gundersen method. RESULTS: Immunohistochemical staining for flt-4 resulted in successful labeling of lymph capillaries in adult human myocardium. Lymph capillary density was calculated as 50.7 +/- 12.5 per mm2 and average diameter was 3.7 +/- 0.7 microm. Conclusions. Lymph capillary morphology in human myocardium may be successfully determined by immunohistochemical staining for flt-4. Tissue samples as small as myocardial biopsies may be used for analysis. Using this method, morphological changes in myocardial lymphatics may be investigated in various cardiovascular diseases.

Reduction of myocardial reperfusion injury by high-dose beta-blockade with esmolol.

BACKGROUND: Myocardial ischemia reperfusion injury may be reduced by beta-blockade. However, how myocardial salvage is affected when beta-blockade is limited to the reperfusion period is unknown. We investigated the impact of CPB and esmolol during reperfusion on infarct size and left ventricular function in two different experimental models of acute myocardial ischemia. METHODS: In open-chest dogs, myocardial ischemia was induced by LAD occlusion in both studies. In study 1, infarct size (TTZ stain) and myocardial water content (MWC, microgravimetry) were determined, comparing reperfusion with blood and esmolol to blood without additives. Study 2 investigated the impact of esmolol on LV function (sonomicrometry, echocardiography) and MWC (microgravimetry) compared to warm blood cardioplegia in a more clinically oriented model. RESULTS: Infarct size and MWC in reperfused myocardium were significantly reduced by esmolol during reperfusion. Global LV function was better preserved in the esmolol group, whereas no difference was seen regarding regional function. CONCLUSIONS: Myocardial salvage may be significantly enhanced by CPB and esmolol, even when treatment with esmolol is initiated as late as with the onset of reperfusion.

Impact of hematocrit value after coronary artery surgery on perioperative myocardial infarction rate.

BACKGROUND: The optimal hematocrit (HCT) value after coronary artery bypass grafting on cardiopulmonary bypass (CPB) has not yet been established. The purpose of our retrospective study was to investigate the association between HCr at the time of entry into the ICU and perioperative Ml rate. METHODS: We reviewed the charts of 500 consecutive coronary artery surgery patients with respect to biometric data, operative procedure, aprotinin or tranexamic acid use, perioperative drainage blood loss and transfusion requirements, perioperative Ml, ICU stay and hospital mortality. Perioperative Ml was defined as new Q-wave on ECG and CK-MB 250U/I. Patients were categorized into three groups depending on their HCr value at the time of entry into the ICU: low (HCTcu 27%): medium (HCr,cu 28% to 32%); high(HCTrcu > or =33%). RESULTS: Age, gender distribution, preoperative LV function, and previous Ml rate were similar between the three groups. Low HCT patients (n -133) received 3.1 +/- 1.0 (Mean + SD) grafts during 55 +/- 19 minutes aortic cross clamp time, 98 +/- 31 minutes on CPB (medium HCT: n = 257; 3.2 +/- 1.0 grafts, 51 +/- 20 min cross clamp time, 93 +/- 30 min CPB; p - 0.45 vs. low HCT; high HCT: n = 110: 3.3 +/- 1:0 grafts; 53 +/- 20 min cross clamp time; 104 +/- 38 min CPB; p = 0.02 vs. medium HCT). The perioperative Ml rate was 3.8% in the low, 4.3% in the medium, and 6.4% in the high-HCr group (p =0.59 ). Intraoperative red blood cell and fresh frozen plasma transfusions were similar between the groups. In the low-HCa group, 53.4% of the patients received aprotinin during the procedure (medium HCa: 65.4%; high HCT: 77.3%; p<0.001). Drainage blood loss during the first 24 hours on ICU was 834 +/- 453 ml in the low, 757 +/- 485 ml in the medium (p -0.44 vs. low), and 640 +/- 353 ml in the high-HCr group (p = 0.003 vs. low). Postoperative red blood cell and fresh frozen plasma transfusions were highest in the low-HCa group(p<0.001). ICU stay was similar between the groups. Hospital mortality was 0.75% in the low, 1.9% in the medium, and 4.5%in the high-HCa group (p = 0.12). CONCLUSIONS: In this retrospective analysis of 500 consecutive coronary artery surgery patients, we did not find any association between perioperative Ml rate and HCr value on entry into the ICU. These results do not support the recent suggestion that low HCT at the time of entry into the ICU protects against perioperative Ml.

Beta-blockade in 200 coronary bypass grafting procedures.

BACKGROUND: Continuous perfusion of the coronary arteries with high-dose beta-blocker (esmolol)-enriched blood has been shown to represent an alternative for myocardial protection during coronary bypass grafting (CABG). Here, we will report on our experience in 200 unselected consecutive cases where this technique was used. METHODS: Eighty percent of the patients (age: 63.3 +/- 0.6 years, ejection fraction: 60 +/- 1.2 %, emergency cases: 11 %) had 3-vessel disease, 34 % had a history of myocardial infarction within less than 90 days preoperatively. The Euro score amounted to 6 +/- 0.3. During 52 +/- 1.2 min of aortic cross-clamp time on normothermic cardiopulmonary bypass, 2.9 +/- 0.1 distal anastomoses were performed on a slow hypocontractile beating heart induced by continuous infusion of 788 +/- 20 mg esmolol per operation. All data: mean +/- SEM. RESULTS: Postoperatively, patients were ventilated for 25 +/- 5.1 hours and stayed on ICU for 2.3 +/- 0.3 days. The postoperative myocardial infarction rate was 4%. Patients left the hospital after 11.2 +/- 0.4 days. Thirty-day mortality was 2.5 %, and 3-month mortality was 3 %. CONCLUSIONS: High-dose beta-blockade is a safe and effective technique in CABG procedures. It may be especially advantageous in high-risk patients.

Cardiopulmonary bypass copolymer surface modification reduces neither blood loss nor transfusions in coronary artery surgery.

OBJECTIVE: Surface-modifying additives (SMA) have been suggested for improving cardiopulmonary bypass (CPB) circuit biocompatibility, potentially minimizing inflammatory complications and bleeding associated with CPB. The purpose of this prospective, randomized clinical study was to compare a novel copolymer surface-modified CPB circuit (SMARXT; COBE Cardiovascular) against the unmodified circuit. METHODS: We randomized 122 patients with isolated coronary artery disease subjected to first-time surgery on CPB into either the SMA (n = 62) or the control group (n = 60). Exclusion criteria included renal insufficiency, liver disease, coagulopathy, anticoagulation therapy < 6 days preop, carotid artery stenosis > 70 %, and a history of stroke. We collected perioperative clinical data including drainage blood loss, transfusion requirements, duration of mechanical ventilation, and ICU stay. Platelet function was determined pre- and post-CPB. RESULTS: SMA patients received 3.2 +/- 0.9 (SD) grafts during 48 +/- 16 min of aortic cross clamp and 91 +/- 30 min CPB (Control: 3.0 +/- 0.9 grafts; p = 0.33, 46 +/- 14 min AXC; p = 0.36, and 84 +/- 23 min CPB; p = 0.14). In the SMA group, 23 patients (37 %) received red blood-cell transfusions, 9 patients (15 %) fresh frozen plasma, and 3 patients (5 %) received platelets (control: n = 27 [46 %], p = 0.44; n = 10 [17 %], p = 0.91; and n=4 [7 %], p = 0.71, respectively). Platelet count on CPB fell to the same level in both groups. In SMA patients, platelet function decreased from 94.2 +/- 24.9 % pre-CPB to 79.5 +/- 32.8 % post-CPB (p = 0.043) (control: from 87.7 +/- 25.6 % to 69.4 +/- 34.7 %; p = 0.001). Postoperative drainage blood loss, mechanical ventilation duration, and ICU stay were similar in both groups (p > 0.3). One patient of the control group was excluded due to surgical bleeding, and one SMA patient died. CONCLUSIONS: Our results show that the surface-modified CPB circuit decreased neither blood loss nor transfusions despite slightly better platelet function preservation compared to the unmodified circuit. This type of CPB circuit surface modification does not appear to improve clinical outcome in low-risk coronary artery surgery patients.

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.

Impact of myocardial protection during coronary bypass surgery on patient outcome.

We have recently shown that continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker Esmolol (ES) improves functional and structural myocardial protection during coronary artery surgery as compared with conventional cardioplegia (CP). The purpose of the present study was to compare both myocardial protection techniques in terms of patient outcome. We retrospectively analyzed the charts of 150 consecutive patients subjected to coronary artery surgery using the ES-technique; 150 patients matched for age, gender, preoperative left ventricular function, history of renal failure, and history of neurological symptoms undergoing surgery with conventional CP during the same time period served as control group. There were no significant differences between both groups with respect to perioperative myocardial infarction rate, need for positive inotropic medication, need for mechanical circulatory support, duration of mechanical ventilation, duration of intensive care unit stay, time of mobilization, postoperative renal failure, cardiac arrhythmias, neurological symptoms, infections or in-hospital mortality. ES-patients were less frequently readmitted to the intensive care unit (ES: 3/150; 2.2% [95% confidence interval: 0-4.2%] vs. CP: 13/150; 8.7% [4.2-13.2%]; P=0.010) and total hospital stay was shorter (ES: 12.3+/-4.8 days [95% CI: 11.5-13.0] vs CP: 13.5+/-3.8 [12.9-14.1] days; P=0.0013), thus saving 159 patient days on the normal ward. Procedural costs were less for the ES-technique (US$ 60 per patient) as compared to the cardioplegia technique (US$ 120 per patient). These data suggest that myocardial protection using the ES-technique does not improve clinical outcome in patients subjected to routine coronary artery surgery, but may save costs.

[Schizencephaly: report of eleven cases]. / Esquizencafalia: relato de onze casos.

A retrospective study comparing clinical and computerized tomography (CT) in 11 patients diagnosed as having schizencephaly was conducted. Seven of these patients were girls and four boys. Six of them had tetraparesis, three hemiparesis and one no motor deficits. Six had epilepsy and ten developmental delay. On CT examinations, 7 patients were found as having bilateral clefts and four unilateral defect. Eight had opened lip clefts and four had a closed lip defect. The commonest associated anomaly was an absent septum pellucidum (n=9), followed by subependymal nodules (n=4), hydrocephalus (n=2) and microcephaly (n=1). Despite magnetic resonance image is the gold-standard to diagnose neuronal migration anomalies, CT can be useful in showing typical aspects of schizencephaly.

Esmolol and cardiopulmonary bypass during reperfusion reduce myocardial infarct size in dogs.

BACKGROUND: Infarct size can be reduced by beta-blockade in acute myocardial ischemia. However it is unknown whether myocardial salvage is still effective when beta-blockade is limited to reperfusion. METHODS: After initiation of cardiopulmonary bypass, 20 dogs were submitted to 2 hours of regional left ventricular ischemia, followed by 2 hours of reperfusion. In 11 dogs beta-blockade was started with the onset of reperfusion (esmolol group). The remaining dogs received no treatment (control, n = 9). Infarct size was determined by tetrazolium chloride staining. Myocardial water content (MWC) and ultrastructural damage (electronmicroscopy) were determined from transmural biopsies. RESULTS: Infarct size was significantly smaller in the esmolol group compared with control (49% versus 68%, p < 0.05). After 2 hours ischemia there was no difference in MWC between groups, whereas after 2 hours reperfusion MWC of ischemic myocardium was significantly lower in the esmolol group than in the control (p < 0.05). Ultrastructural changes were typical for ischemia-reperfusion injury in both groups. CONCLUSIONS: Beta-blockade may be cardioprotective during reperfusion through various mechanisms and may enhance myocardial salvage, even when treatment is initiated as late as with the onset of reperfusion.

[Risk stratification in heart surgery: do risk scores facilitate the determination of indications?]. / Risikostratifizierung in der Herzchirurgie--Entscheidungshilfe bei der Indikationsstellung.

Various risk scores have been developed for the assessment of operative risk in cardiac surgery. Although risk stratification has been acknowledged as a useful tool to analyze trends in therapy and changes in patient populations, its relevance in assessing the indication for surgery has been questioned. It was the goal of this prospective study to compare 6 common risk scores with regard to the predictive value for mortality in individual patients. Between September 1998 and February 1999 all adult patients undergoing heart surgery were prospectively scored according to the following scores: initial Parsonnet, Cleveland Clinic, French, Euro, Pons, and the Ontario Province Risk score. Early lethality was assessed within 30 days postoperatively. Follow-up was completed in 504 patients. With the exception of the Ontario Province Risk score, lethality in the high risk group was overestimated by all scores, whereas lethality in low to moderate risk groups was underestimated by several scores. Mean scores of surviving and deceased patients showed a broad overlap with high standard deviations. Preoperative risk scores are effective tools for stratification of patient populations and the analysis of surgical outcome. With the aid of risk scores, operative risk can be sufficiently predicted for patient populations or subpopulations. The Euro score best predicted the outcome of our patients. However, when the indication for surgery is to be determined in an individual patient, risk scores should be only considered as an orientation in the decision process.