Christoph Benk

Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease.

OBJECTIVE Outcomes after ventricular assist device (VAD) implantation have significantly improved during the last decade. However, bleeding episodes remain a serious complication of VAD support. This cannot be explained by the individual anticoagulation regimen alone in several cases, but may be symptomatic of acquired von Willebrand disease (VWD). The leading finding in acquired VWD (AVWD) is the loss of large multimers which results in diminished binding to collagen and to the platelets. We, therefore, analysed patients with two VAD types for laboratory parameters of VWD and compared them with patients after heart transplantation (HTX). MATERIALS AND METHODS Seven patients with a HeartMate II left-ventricular assist device and five patients who received a Thoratec biventricular assist device were included in this study. Eight HTX recipients served as controls. Analysis included international normalized ratio (INR), partial thromboplastin time (PTT), platelet count, von Willebrand factor (VWF) antigen, collagen binding capacity, ristocetin cofactor activity, the ratios of the latter two to the VWF antigen and presence of large VWF multimers. RESULTS The VAD and HTX groups did not differ with regard to age or time-point of analysis after surgery. INR and number of platelets were comparable in both groups, PTT was prolonged in VAD patients. Both VAD and HTX patients had elevated but comparable amounts of VWF antigen. However, large multimers were missing in all of 10 tested VAD patients. In contrast, five of six tested HTX recipients displayed normal multimer pattern. Indeed, collagen binding capacity and ristocetin cofactor activity (which measures binding of VWF to platelets) were lower in VAD patients compared to HTX recipients. Impaired coagulation associated with VADs was also reflected by the diminished ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. A pathologic collagen binding ratio was found in all 10 tested VAD patients and one of the eight HTX patients, a reduced ristocetin cofactor activity ratio in 10 of 12 VAD and one of eight HTX patients. CONCLUSION Non-surgical postoperative bleeding after VAD implantation could be explained by an AVWD. Several pharmacologic treatment options (tranexamic acid, desmopressin, VWF-factor VIII concentrate, recombinant factor VIIa) may arise from our data. Improved VAD design could prevent this problem in the future.

Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS)

PurposeExtracorporeal life support (ECLS) is used for patients with refractory heart failure with or without respiratory failure. This temporary support is provided by blood pumps which are connected to large vessels. Bleeding episodes are a typical complication in patients with ECLS. Recently, several studies illustrated that acquired von Willebrand syndrome (AVWS) can contribute to bleeding tendencies in patients with long-term ventricular assist devices (VAD). AVWS is characterized by loss of the high molecular weight (HMW) multimers of von Willebrand factor (VWF) as a result of high shear stress and leads to impaired binding of VWF to platelets and to subendothelial matrix. Since ECLS and VAD share several features, we investigated patients with ECLS for AVWS.MethodsWe analyzed 32 patients with ECLS and 19 of them without support. To diagnose AVWS, ratios of ristocetin cofactor activity (VWF:RCo) and collagen binding capacity (VWF:CB) to VWF antigen (VWF:Ag) were employed in conjunction with multimeric analysis.ResultsReduced VWF:RCo/VWF:Ag ratios were identified in 28 ECLS patients. Furthermore, VWF:CB/VWF:Ag ratios were decreased in 31 patients. HMW multimers of VWF were missing in the same 31 patients. Thus, 31 of 32 ECLS patients presented with AVWS. Twenty-two of the 32 patients suffered from bleeding complications. Without support, AVWS was not detectable in any analyzed patient.ConclusionOur data indicate that AVWS is a typical disorder in patients with ECLS. We hypothesize that AVWS could contribute to aggravation of bleeding tendencies in ECLS patients.

Position article for the use of extracorporeal life support in adult patients

Extracorporeal life support (ECLS) is one of the recent fields in cardiac surgery which has improved significantly the quality of patient care in acute or chronic end-stage heart disease. The safe use of this new technology requires many different prerequisites which are summarized in this position article. It includes the necessary personnel and their qualifications, the structural assumptions, the required equipment, and the parameters which have to be monitored for the safe usage of these devices. In addition, indications and contraindications for ECLS, the management and control of a wide range of parameters related to the extracorporeal circulation, as well as the necessary equipment are described. Quality assurance and education are also described in this position article.

Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart.

Unexplained bleeding episodes are associated with ventricular assist devices (VAD) and can occur in part due to acquired von Willebrand syndrome (AVWS). AVWS is characterised by loss of high molecular weight (HMW) multimers of von Willebrand factor (VWF) and decreased ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. Loss of multimers can occur as VWF is subjected to increased shear stress, which occurs in presence of VADs. We studied 12 patients who required mechanical support of their native heart for terminal cardiac insufficiency. Nine patients underwent placement of a VAD, while three underwent placement of a total artificial heart (TAH), which is connected directly to heart and large cardiac vessels without cannulas. Within one day of VAD implantation, four of five patients evaluated demonstrated loss of HMW multimers and impaired VWF function. AVWS was present within two weeks of implantation in eight of nine patients, and in all seven tested patients after >/=3 months. Patients with different VAD types developed varying severities of AVWS. After VAD explantation, HMW multimers were detectable and VWF function normalised in all patients. AVWS was not observed in the TAH patients studied. Our findings demonstrate that patients with an implanted VAD experience a rapid onset of AVWS that is quickly and completely reversed after device explantation. In addition, TAH patients do not develop AVWS. These results suggest that shear stress associated with exposure of blood to VAD cannulas and tubes may contribute to the development of AVWS.

Haemolysis in patients with ventricular assist devices: major differences between systems

INTRODUCTION Implantation of a ventricular assist device (VAD) is a seminal therapeutic option for patients with terminal cardiac failure. However, haemolysis remains a clinically relevant adverse effect of several VAD types. Lysed erythrocytes release lactate dehydrogenase (LDH) and haemoglobin. Free haemoglobin in plasma is bound by haptoglobin with high affinity. The complex is internalised by monocytes/macrophages and degraded. Any more released free haemoglobin is captured by haemopexin. This complex also undergoes lysosomal degradation in various cells. Only now, the excessive free haemoglobin can be measured in plasma. Here, we investigated haemolysis in patients supported by different VAD types. METHODS Five patients with an intracorporeal centrifugal left ventricular VAD (LVAD), 10 patients with an axial LVAD and seven patients with a paracorporeal biventricular assist device (BVAD) were analysed preoperatively and 3 days (3.0+/-0.4 days, early), 2 weeks (14+/-1 days, intermediate) and 2 months (62+/-5 days, later) after VAD implantation for haptoglobin, haemopexin, free haemoglobin in plasma, LDH, total haemoglobin, haematocrit and transfusion requirements. RESULTS Patients with a centrifugal LVAD displayed normal haptoglobin and haemopexin, low free haemoglobin and moderately increased LDH. In comparison, axial LVADs were accompanied by lower haptoglobin and haemopexin and higher free haemoglobin and LDH values. In contrast, BVADs led to an almost complete loss of haptoglobin and haemopexin and to high levels of free haemoglobin and LDH at each analysed time point. CONCLUSIONS While severe haemolysis accompanies BVAD support, erythrocyte damage is less pronounced in the axial LVAD examined and only slight in the intracorporeal centrifugal LVAD. Haemopexin, a scavenger of free haemoglobin, can be used, in combination with haptoglobin and free haemoglobin, to assess erythrocyte damage.

Pulsatile Pulmonary Perfusion During Cardiopulmonary Bypass Reduces the Pulmonary Inflammatory Response

BACKGROUND Pulmonary dysfunction presumably linked to an inflammatory response is frequent after cardiac operations using cardiopulmonary bypass (CPB) and pulmonary hypoperfusion. We previously demonstrated that active perfusion of the lungs during CPB reduces ischemic lung injury. We now hypothesized that avoiding ischemia of the lungs during CPB by active pulmonary perfusion would decrease pulmonary inflammatory response. METHODS Pigs were randomized to a control group with CPB for 120 minutes, followed by 120 minutes of postbypass reperfusion, or to the study groups where animals underwent active pulmonary perfusion with pulsatile or nonpulsatile perfusion during CPB (n = 7 in each group). Activation of transcription factor activity (nuclear factor [NF]-kappaB and activating protein [AP]-1) was determined by electrophoretic mobility shift assay. Levels of proinflammatory protein expression (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha) were quantified by enzyme-linked immunoabsorbent assay. Caspase-3 activity was measured using a fluorogenic assay. RESULTS The activation of transcription factor AP-1 and NF-kappaB was reduced in the pulsatile pulmonary perfusion group. The caspase-3 activity and the expression of IL-1, IL-6, and TNF-alpha revealed a significant decrease in the pulsatile and nonpulsatile pulmonary perfusion groups. Animals of the pulsatile pulmonary perfusion group showed significantly reduced IL-6 expression and caspase-3 activity compared with the nonpulsatile pulmonary perfusion group. CONCLUSIONS Active pulmonary perfusion reduces the inflammatory response and apoptosis in the lungs observed during conventional CPB. This effect is greatest when pulmonary perfusion is performed with pulsatility. The reduction in cytokine expression by pulsatile pulmonary perfusion might be mediated by AP-1 and NF-kappaB.

Trans-catheter closure of the native aortic valve with an Amplatzer® Occluder to treat progressive aortic regurgitation after implantation of a left-ventricular assist device

We report on a patient with ischaemic dilated cardiomyopathy, who developed progressive regurgitation of his native aortic valve after implantation of a left-ventricular assist device (LVAD, HeartMate II). Increasing regurgitant volume led to reduced effective cardiac output and worsening of symptoms. To overcome aortic regurgitation, we successfully closed his aortic valve minimally invasively using the Amplatzer(®) P.I. Muscular VSD Occluder. This led to instant haemodynamic stabilisation. We observed significant residual regurgitation through the Occluder during the initial phase, which led temporarily to increased haemolysis and subsequently to worsening of kidney function; once the haemolysis ceased, we noted a very good interventional and clinical result at short-term follow-up.

Successful resuscitation after prolonged periods of cardiac arrest: A new field in cardiac surgery

OBJECTIVE Cardiopulmonary resuscitation is associated with high mortality and poor neurological recovery. Cardiopulmonary resuscitation can cause ischemia-reperfusion injury of the whole body and brain. We assessed the hypothesis that controlled reperfusion of the whole body with cardiopulmonary bypass would limit reperfusion injury after 15 minutes of normothermic cardiac arrest with better survival and neurological recovery. METHODS Eleven pigs were exposed to normothermic ischemia for 15 minutes by inducing ventricular fibrillation, followed by cardiopulmonary resuscitation (control group, n = 4) or 60 minutes of cardiopulmonary bypass (treatment group, n = 7). Conditions of reperfusion and the reperfusate were controlled with cardiopulmonary bypass. Animals were observed for up to 7 days, and neurological assessment (Neurological Deficit Score: 0, normal; 500, brain death), magnetic resonance imaging, and brain histology were performed. RESULTS All animals in the control group died after 20 minutes of cardiopulmonary resuscitation (n = 4). All (n = 7) survived in the treatment group. Clinically apparent neurological recovery occurred within 24 hours; 1 fully conscious pig could not walk. The Neurological Deficit Score was 98 +/- 31 in all animals (n = 7) after 24 hours and decreased to 0 after 48 hours in 4 of 5 eligible animals; 1 animal had a Neurological Deficit Score of 110 after 3 days. Brain histology revealed hypoxic and apoptotic neurons with an inconclusive correlation regarding neurological recovery. CONCLUSION Clinically apparent neurological recovery after a period of 15 minutes of cardiac arrest occurred with cardiopulmonary bypass instead of cardiopulmonary resuscitation for reperfusing the whole body. This approach contrasts with cardiopulmonary resuscitation, in which resuscitation has been reported as successful after only 3 to 5 minutes of cardiac arrest. Cardiopulmonary bypass might be a key to improve survival and neurological recovery after cardiac arrest.

Acute fibrinous and organizing pneumonia associated with influenza A/H1N1 pneumonia after lung transplantation

BackgroundImmunocompromised patients, particularly after lung transplantation, are at high risk to develop atypical forms of pulmonary infections including influenza A/H1N1. Acute Fibrinous and Organizing Pneumonia (AFOP) is a special histological pattern in acute respiratory failure with high mortality.Case presentationWe describe a 66-year-old woman with double lung transplantation in August 2009 due to end stage pulmonary fibrosis. After prolonged weaning and subsequent promising course, she developed atypical pneumonia with diffuse pulmonary infiltrates in both lungs in January 2010. Infection with influenza A/H1N1 virus was verified. The patient rapidly suffered from respiratory insufficiency and died eight days after this diagnosis. The post-mortem revealed especially in the lower parts of the lungs the classical histological pattern of pure AFOP. Molecular analyses of lung tissue were positive for influenza A/H1N1.ConclusionTo our knowledge we present the first case of AFOP triggered by viral infection, here proven to be influenza virus A/H1N1. Thus, also in the setting of viral infection the highly deadly differential diagnosis of AFOP must be considered.

High colloid oncotic pressure priming of cardiopulmonary bypass in neonates and infants: implications on haemofiltration, weight gain and renal function

OBJECTIVE To evaluate the influence of high colloid oncotic pressure (COP) priming of cardiopulmonary bypass (CPB) on fluid balances, haemofiltration, capillary leakage and renal function in neonates and infants. METHODS Twenty neonates or infants underwent heart surgery using CPB and were randomised in two groups. For group 1 (FFP-group) a blood priming with fresh frozen plasma (FFP, low oncotic pressure) was chosen, for group 2 (HA-group) a blood priming containing FFP and human albumin 20% (HA) to realise higher oncotic pressures was substituted. All patients were monitored before, during and 6h after CPB. We measured weights, fluid balances, transfusion volumes, colloid oncotic pressures, inflammatory parameters (c-reactive protein, interleukin-6, interleukin-8, thrombocytes, leucocytes) and renal function (creatinine clearances, renal protein losses). RESULTS Patients demographics and operational procedures were comparable in both groups with no further differences in operation procedures regarding palliation or correction. Colloid oncotic pressures of the priming solutions were higher in the HA-group (28 mmHg+/-4.9) than in the FFP-group (6 mmHg+/-1.3, p<0.001). Relative weight gain as a marker of capillary leakage in the HA-group (2%+/-4.5) was significantly lower 6h post CPB than in the FFP-group (8%+/-8.0, p=0.015). Haemofiltration rates were higher in the HA-group (569 ml+/-197 vs 282 ml+/-157, p=0.002) on CPB. There were no differences of creatinine clearances 6h after the end of CPB. Renal protein losses were elevated in both groups without any inter-group differences during and 6h after CPB. CONCLUSION Addition of concentrated human albumin to priming fluids in paediatric cardiac surgery leads to less weight gain even after CPB. Supplementing paediatric patients undergoing cardiac surgery with concentrated human albumin does not affect renal function more severely than in paediatric patients undergoing cardiac surgery on CPB with blood priming.