Stefan Christiansen

Anticoagulative management of patients requiring left ventricular assist device implantation and suffering from heparin-induced thrombocytopenia type II

BACKGROUND Heparin-induced thrombocytopenia type II (HIT II) is a rare but life-threatening side effect of heparin therapy. We describe the perioperative anticoagulative management of patients tested positive for HIT II and requiring implantation of a left ventricular assist device (LVAD). METHODS We report on 3 patients with a different perioperative anticoagulative management (preoperative, intraoperative, and postoperative anticoagulation with danaparoid-sodium; preoperative anticoagulation with recombinant hirudin, anticoagulation with danaparoid-sodium intraoperatively and postoperatively; preoperative anticoagulation with recombinant hirudin, intraoperative anticoagulation with heparin, and postoperative anticoagulation with danaparoid-sodium) and discuss the difficulties of the treatment. RESULTS Anticoagulation with alternative drugs such as recombinant hirudin and danaparoid-sodium led to serious and life-threatening bleeding complications as well as to thromboembolic events in the first 2 patients. Therefore the third patient underwent LVAD implantation using heparin for intraoperative anticoagulation to avoid administration of high doses of recombinant hirudin or danaparoid-sodium. Despite very low anti-factor Xa activities, when using danaparoid-sodium postoperatively, the patient suffered from a bleeding complication on the 4th day after LVAD implantation requiring reexploration. CONCLUSIONS In selected cases (negative heparin-induced platelet aggregation (HIPA) test at the time of LVAD implantation and continuation of postoperative anticoagulation with recombinant hirudin or danaparoid-sodium), heparin may be used for LVAD implantation in HIT II patients to reduce bleeding complications.

Alteration of matrix metalloproteinases in selective left ventricular adriamycin-induced cardiomyopathy in the pig.

INTRODUCTION Anthracyclines are widely used in oncogenic therapy. Owing to their cardiotoxic side effects, their application is subdued to dose limitations. Many cardioprotective approaches have failed. This study examined the role of matrix metalloproteinases (MMP) in the remodeling process of extracellular matrix after treatment with doxorubicin (Adriamycin) as a toehold for a new therapeutic approach, for example, treatment with MMP inhibitors. METHODS Severe heart failure was induced in 6 pigs by the repetitive intracoronary application of Adriamycin. Degree of dilatation and insufficiency were measured by echocardiography and hemodynamics. Before and after treatment, MMP activity (fluorogenic assay: MMP-1, MMP-2) and gene expression (reverse transcription-polymerase chain reaction [RT-PCR]: MMP-1, -2, -9; membrane type-1 matrix metalloproteinase, [MT1MMP]; tissue inhibitor of metalloproteinase 1 [TIMP-1]) were measured. Spatial distribution of MMP-1, MMP-2, and collagen were visualized in antibody-stained frozen sections. One-way analysis of variance was used for data analysis. RESULTS Severe myocardial insufficiency (ejection fractions < 50% of baseline values) developed in all animals. No severe side effects were encountered. We found a strong activation of MMP-1 and MMP-2 in fluorogenic and PCR assays. RT-PCR revealed a significant activation of MMP-9 and MT1-MMP and a weaker induction of TIMP-1. Histology showed typical signs of myocardial fibrosis, with myocardial cell loss, collagen disorder, and vacuoles. CONCLUSION We showed a strong transcriptional activation for several specific MMPs in Adriamycin-induced cardiac remodeling. Contrary to published data on myocardial infarction, early inhibitory therapy before myocardial injury is possible in Adriamycin-treated patients. Local application by our catheter-based system would additionally help to avoid systemic side effects.

A new right ventricular assist device for right ventricular support

Right ventricular support by mechanical devices for postcardiotomy right heart failure is still associated with a high mortality. We report on the first use of a new paracardiac microaxial blood pump for postcardiotomy right heart failure in two patients undergoing emergency coronary artery bypass grafting (the first patient for a myocardial infarction complicated by a left ventricular wall rupture, the second patient for a dissection of the right coronary artery after an interventional procedure).

Partial left ventriculectomy in modified adriamycin-induced cardiomyopathy in the dog.

BACKGROUND The purpose of this study was to evaluate modified adriamycin-induced cardiomyopathy in the dog for research on partial left ventriculectomy (PLV). METHODS An intracoronary catheter was introduced into the left main stem via the first marginal branch in a retrograde fashion in 12 adult foxhound dogs. The catheter was connected to a percutaneous access port that was used for weekly adriamycin administration (10 mg over a 1-hour period on 5 occasions). Follow-up examinations (transthoracic echocardiography, hemodynamic parameters, cardiopulmonary status, neurohormones) were done before, 1 week after the last adriamycin administration, and then 6 weeks later. This protocol was performed in 6 dogs (control group: Group 1). The other 6 dogs underwent PLV 1 week after the last adriamycin administration (Group 2). After the last measurements, all dogs were killed with saturated potassium chloride under general anesthesia and the hearts were excised for histologic examination. All data were calculated as mean and standard error of the mean. Differences were calculated by the Wilcoxon signed-rank test for paired and unpaired data. p < 0.05 was considered statistically significant. RESULTS One dog from each group died suddenly during adriamycin administration (probably due to ventricular arrhythmia). In addition, 1 dog from Group 2 suffered from a severe systemic inflammatory response syndrome after PLV and died 36 hours after surgery. Thus, 5 dogs from Group 1 and 4 from Group 2 underwent the entire study protocol. Adriamycin administration resulted in a severe dilated cardiomyopathy that was comparable in both groups (significant increase of central venous pressure, mean pulmonary artery pressure, pulmonary wedge pressure, left ventricular end-systolic and end-diastolic diameters, oxygen extraction, troponin I and anti-diuretic hormone, whereas cardiac output, ejection fraction and venous oxygen saturation decreased significantly). Deterioration of cardiac function continued after termination of adriamycin administration in Group 1 dogs, albeit not as progressively as during adriamycin administration. In contrast, cardiac function improved in Group 2 dogs after PLV, but did not reach baseline values. Cardiac index increased and oxygen extraction (p = 0.03) decreased, resulting in an enhanced venous oxygen saturation (p = 0.02). In particular, the distance of the papillary muscles at end diastole (p = 0.02) and at end systole (p = 0.02) at the mid-papillary level decreased significantly after PLV, resulting in reduced left ventricular diameter and volume (statistically significant for left ventricular end-systolic diameter and volume). All hearts had severe histologic alterations characteristic of adriamycin-induced toxicity, including cytoplasmic vacuolation, myocyte degeneration and increased fibrosis. CONCLUSION Modified adriamycin-induced cardiomyopathy in the dog may be suitable for research on PLV.

Surgical Management of a Left Main Stem Coronary Artery Aneurysm

Abstract  Left main stem aneurysms are rarely described and the optimal treatment is controversially discussed. A majority of these patients undergo medical treatment with antiplatelet or anticoagulation drugs. Surgery is just recommended in symptomatic patients or when there is the risk of thromboembolic events or rupture. We report on a 51‐year‐old patient suffering from intermittent angina pectoris in whom an aneurysm of the left main stem was diagnosed by coronary angiography. The patient underwent successful surgical management with aneurysm closure and reconstruction of the left main stem by a segment of the great saphenous vein. This report summarizes the main treatment options for left main stem aneurysms and discusses the role of cardiac surgery for this rare disease.

Successful cardiac transplantation after 4 cases of DeBakey left ventricular assist device failure

Left ventricular assist devices (LVADs) are an established surgical therapy for patients with end-stage heart failure as a bridge to cardiac transplantation. Major disadvantages of these devices are thromboembolic events, bleeding complications, infections, and malfunctions. We report on our experiences with DeBakey LVAD malfunctions requiring LVAD exchange in 4 patients. All patients underwent subsequent cardiac transplantation and are doing well now.

Preoperative immunoglobulin treatment in patients with Werlhof’s disease undergoing cardiac operation

BACKGROUND Patients with Werlhofs disease and undergoing a cardiac surgical procedure with cardiopulmonary bypass are at increased risk for bleeding complications. We report the usefulness of preoperative immunoglobulin treatment in selected patients. METHODS Between May 1995 and July 1998, 10 patients with Werlhofs disease underwent a cardiac surgical procedure with cardiopulmonary bypass in our department. Five patients with mean platelet counts of less than 80x10(9)/L received immunoglobulin therapy preoperatively (group 1). The other 5 patients with mean platelet counts higher than 80x10(9)/L were not so treated (group 2). RESULTS In group 1, mean platelet count increased from 54x10(9)/L 5 days before operation to 112x10(9)/L after immunoglobulin treatment (p = 0.018) and did not fall to less than 60x10(9)/L postoperatively. Patients in group 1 received 16 units of packed red blood cells and 5 units of platelet concentrate. Patients in group 2 required 24 units of packed red blood cells, 5 units of platelet concentrate, and 23 units of fresh frozen plasma. Only 1 patient (group 2) had a surgical bleeding complication that required reexploration. Mean drainage loss was 1,100 mL in group 1 and 1,210 mL in group 2. CONCLUSIONS Our data demonstrate that immunoglobulin treatment of patients with Werlhofs disease and mean platelet counts of less than 80x10(9)/L significantly augments platelet counts preoperatively. It may be useful in selected patients.

Selective Left Ventricular Adriamycin-Induced Cardiomyopathy in the Pig

OBJECTIVE The aim of this study was the development of an experimental cardiomyopathy induced with Adriamycin (Pharmacia & Upjohn, Erlangen, Germany) with selective toxic damage of the left ventricular myocardium that avoided an ischemic component. METHODS An intracoronary catheter was implanted directly into the left main stem in pigs and connected to a percutaneous access port that was used for repetitive Adriamycin administration (3-5 x 25 mg weekly over a 1-hour period). Hemodynamic and echocardiographic variables were measured before Adriamycin administration, 1 week after, and at 4 weeks. Thereafter, all hearts were autopsied for detailed histologic examination. Statistical analysis was done by an analysis of variance for multiple parameters. RESULTS All pigs had normal baseline cardiac function. Measurements after Adriamycin administration and 4 weeks later demonstrated a continued increase of the central venous pressure, pulmonary artery pressure, pulmonary wedge pressure, and pulmonary vascular resistance, whereas cardiac output, stroke volume index, and left ventricular stroke work index decreased. These results were supported by the echocardiographic data depicting an increase of left ventricular diameters and volumes, accompanied by a decrease of intraventricular and left ventricular posterior wall thickness as well as left ventricular ejection fraction. Right ventricular volumes and function did not change during the trial. The histologic examination of the hearts revealed a selective toxic damage of the left ventricular myocardium with multifocal necroses and advanced tissue reorganization. CONCLUSION This animal model creates a selective left ventricular damage that avoids ischemic damage of the myocardium. Both aspects can improve research on Adriamycin-induced cardiomyopathy, especially preventive or therapeutic strategies.

Treatment of Right Heart Failure with a New Microaxial Blood Pump

Isolated postcardiotomy right ventricular failure is rare but associated with a high mortality. Therefore, new developments reducing this mortality are necessary. We report our first successful clinical use of a new paracardiac right ventricular microaxial blood pump which was developed for postcardiotomy right heart failure.

Are patients with Werlhof's disease at increased risk for bleeding complications when undergoing cardiac surgery?

BACKGROUND It is generally assumed, that patients with Werlhofs disease (WD) are at increased risk for bleeding complications when undergoing cardiac surgery with extracorporeal circulation. Therefore we performed this case control study to estimate the real risk for bleeding complications of these patients. METHODS Between 05/95 and 07/98, ten patients with WD (eight males, two females) underwent cardiac surgery employing extracorporeal circulation (WD-group). Five of these patients with platelet counts below 80/nl were treated by immunoglobulins preoperatively. Each patient with WD was matched to five patients without WD (no-WD-group) using diagnosis, age, gender, ejection fraction, number of distal anastomosis and body-mass-index as matching criteria. RESULTS Mean number of platelet counts were significant lower in the WD-group than in the no-WD-group despite a significant increase of platelet counts after immunoglobulin treatment (54/nl-->112/nl, P=0.018). On the day before, directly after and on the first day after surgery they were 141/nl vs. 215/nl (P=0.012), 75/nl vs. 147/nl (P=0.001) and 93/nl vs. 136/nl (P=0.009). Accordingly, patients of the WD-group received significantly more platelet concentrates than patients of the no-WD-group (mean number of platelet concentrates: 2.3 versus 0.7, P=0.007). Total drainage loss via the mediastinal chest tubes was almost identical (1197 ml in the no-WD-group and 1140 ml in the WD-group). One patient of each group suffered from a bleeding complication requiring reexploration. Three patients of the no-WD-group (6%) and one patient of the WD-group (10%) expired postoperatively unrelated to WD. CONCLUSIONS Patients with WD may possibly undergo cardiac surgery without a markedly enhanced risk for bleeding complications despite a more than usual transfusion requirement and significantly lower platelet counts perioperatively.