Accuracy and precision of transcardiopulmonary thermodilution in patients with cardiogenic shock.

Hemodynamic monitoring plays a crucial role in the supportive treatment of critically ill patients. In this setting, the use of the pulmonary artery catheter (PAC) is a standard procedure. In this study we prospectively compare the accuracy and precision of pulmonary thermodilution (PTD) by PAC and transcardiopulmonary thermodilution (TC-PTD) in patients with cardiogenic shock following an acute cardiac event. In this prospective study 77 hemodynamic measurements were taken in 11 patients presenting cardiogenic shock (CS) treated at the medical intensive care unit of our university hospital. Hemodynamic parameters were measured simultaneously by PTD and by TC-PTD. Both techniques assessed showed a strong correlation in the obtained hemodynamic parameters. The mean bias of cardiac index between measured by PTD (CIpa) and by TC-PTD (CIpi) was 0.04 ± 0.35 L/min/m2. During intra-aortic balloon pump (IABP) counterpulsation and therapeutic hypothermia (TH) in post-resuscitation care, mean bias between CIpa and CIpi was 0.04 ± 0.36 and 0.04 ± 0.34 L/min/m2, respectively. Similarly, patients presenting mitral or tricuspid regurgitation showed interchangeable parameters. Preload parameters obtained by TC-PTD showed significant differences in patients with left ventricular ejection fraction (LVEF) <35 %, compared to patients with LVEF ≥35 %. In contrast, pulmonary arterial occlusion pressure showed no significant difference. Hemodynamic measurements by PTD and TC-PTD are interchangeable during therapy of CS, including patients IABP, TH, mitral or tricuspid regurgitation. Preload parameters measured by TC-PTD seem to be more accurate in these patients than pressure parameters of PTD to gather the acute hemodynamic situation.

Patients with exercise-associated ventricular ectopy present evidence of myocarditis.

BACKGROUND: The origin and clinical relevance of exercise-induced premature ventricular beats (PVBs) in patients without coronary heart disease or cardiomyopathies is unknown. Cardiovascular magnetic resonance enables us to non-invasively assess myocardial scarring and oedema. The purpose of our study was to discover any evidence of myocardial anomalies in patients with exercise-induced ventricular premature beats. METHODS: We examined 162 consecutive patients presenting palpitations and documented exercise-induced premature ventricular beats (PVBs) but no history or evidence of structural heart disease. Results were compared with 70 controls matched for gender and age. ECG-triggered, T2-weighted, fast spin echo triple inversion recovery sequences and late gadolinium enhancement were obtained as well as LV function and dimensions. RESULTS: Structural anomalies in the myocardium and/or pericardium were present in 85 % of patients with exercise-induced PVBs. We observed a significant difference between patients with PVBs and controls in late gadolinium enhancement, that is 68 % presented subepicardial or midmyocardial lesions upon enhancement, whereas only 9 % of the controls did so (p < 0.0001). More patients presented pericardial enhancement (35 %) or pericardial thickening (27 %) compared to controls (21 % and 13 %, p < 0.0001). Myocardial oedema was present in 37 % of the patients and in only one control, p < 0.0001. Left ventricular ejection fraction did not differ between patients and controls (63.1 ± 7.9 vs. 64.7 ± 7.0, p = 0.13). CONCLUSIONS: The majority of patients with exercise-associated premature ventricular beats present evidence of myocardial disease consistent with acute or previous myocarditis or myopericarditis.

Platelet dysfunction and acquired von Willebrand syndrome in patients with left ventricular assist devices.

OBJECTIVES: Unexplained bleeding events are a severe complication in patients with left ventricular assist devices (LVADs). Platelet dysfunction and acquired von Willebrand syndrome (AVWS) may contribute to bleeding tendencies. Yet, comprehensive data with respect to platelet function and AVWS in LVAD patients in terms of bleeding events are scarce. METHODS: Thirty-nine HeartMate II patients were included in this study. Data of at least two time points were available for each patient. Platelet function was analysed via light transmission aggregometry in 19 patients without LVAD, 28 in early (≤14 days) and 30 in late postimplantation states (≥30 days). Von Willebrand factor (VWF) antigen, VWF collagen binding capacity and VWF multimeric analyses were performed in 26 patients without LVAD, 39 in early and 33 in late postimplantation states to diagnose AVWS. Bleeding complications were recorded for 39 patients in the early and 33 in the late postoperative period. RESULTS: Platelet dysfunction was detectable in 18 of 19 without LVAD and in all patients following LVAD implantation. Platelet aggregation values did not change over time (without-early, P = 0.27, n = 14; early-late, P = 0.17, n = 21). AVWS was not diagnosed in patients without LVAD, except for one. On LVAD, 33 of 39 patients had AVWS in the early and all in the late period (n = 33). Bleeding events occurred in 44% of patients in the early and in 64% of patients in the late period. CONCLUSIONS: According to our data, platelet aggregation is often impaired in LVAD patients even without an implanted LVAD. Additionally, appearance of AVWS seems to be closely linked to LVAD implantation.

A high ratio of ADP-TRAP induced platelet aggregation is associated more strongly with increased mortality after coronary stent implantation than high conventional ADP induced aggregation alone.

OBJECTIVE: This study aimed to evaluate whether a high relative ADP induced aggregation (r-ADP-agg) is associated with an increased mortality in patients after coronary stent implantation. BACKGROUND: Several trials were not able to improve clinical outcome by adapting platelet inhibition in patients after coronary stent implantation and high platelet reactivity (HPR). Platelet monitoring is complex and conventional definition of adenosindiphosphate (ADP) induced aggregation alone might not transfer the whole picture of adequate platelet inhibition in vivo. METHODS: In a prospective single-centre observational trial multiple electrode aggregometry was performed in whole blood of patients after stent implantation. r-ADP-agg was defined as the ADP-thrombin receptor activating peptide ratio to reflect an individual degree of P2Y12 dependent platelet inhibition with a cut-off value for HPR of ≥ 50%. The primary end point was mortality. RESULTS: Follow-up was completed in 176 of 184 patients (96%) with a mean follow-up time of 3.7 years. 35 (20 %) patients revealed an r-ADP-agg ≥ 50%. An r-ADP-agg ≥ 50% was associated with an increased mortality [unadjusted hazard ratio (HR) 7.006 (2.561-19.17); p = 0.0001]. In a multivariable Cox regression analysis mortality was independently associated with an r-ADP-agg ≥ 50% [HR 3.324 (1.542-7.165); p = 0.0022], ACS-setting [HR 3.249 (1.322-7.989); p = 0.0102] and severely reduced LV function [HR 5.463 (2.098-14.26); p = 0.0005]. CONCLUSION: An r-ADP-agg ≥ 50% is associated with an increased mortality in patients after coronary stent implantation. Furthermore, r-ADP-agg might represent a better tool to predict clinical outcome than the conventional ADP induced platelet aggregation alone.

Efficacy of Coming Out Proud to reduce stigma's impact among people with mental illness: pilot randomised controlled trial.

BACKGROUND: Facing frequent stigma and discrimination, many people with mental illness have to choose between secrecy and disclosure in different settings. Coming Out Proud (COP), a 3-week peer-led group intervention, offers support in this domain in order to reduce stigma's negative impact. AIMS: To examine COP's efficacy to reduce negative stigma-related outcomes and to promote adaptive coping styles (Current Controlled Trials number: ISRCTN43516734). METHOD: In a pilot randomised controlled trial, 100 participants with mental illness were assigned to COP or a treatment-as-usual control condition. Outcomes included self-stigma, empowerment, stigma stress, secrecy and perceived benefits of disclosure. RESULTS: Intention-to-treat analyses found no effect of COP on self-stigma or empowerment, but positive effects on stigma stress, disclosure-related distress, secrecy and perceived benefits of disclosure. Some effects diminished during the 3-week follow-up period. CONCLUSIONS: Coming Out Proud has immediate positive effects on disclosure- and stigma stress-related variables and may thus alleviate stigma's negative impact.

Predictors of severity of cerebral vasospasm caused by aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm is one of the leading causes of poor outcome after aneurysmal subarachnoid hemorrhage. The risk factors for the development of vasospasm have been evaluated in many clinical studies. However, it remains unclear if vasospasm severity can be predicted. The purpose of this study was to determine if different demographic and clinical factors that appear to be predictors of vasospasm can also prognosticate the severity of cerebral vasospasm. METHODS: We retrospectively analyzed consecutive patients with subarachnoid hemorrhage who underwent endovascular vasospasm treatment in a single center. In order to define predictors of vasospasm severity, we studied the demographic and clinical characteristics of these patients. Vasospasm severity was defined by cerebral angiography, transcranial Doppler ultrasound, and therapeutic response on endovascular treatment. Statistical analyses were performed to determine significant predictors. RESULTS: A total of 70 patients with vasospasm were included. Early onset of mean flow velocities>160 cm/second on transcranial Doppler ultrasound correlated with severity of angiographic vasospasm (P=.0469) and resistance against intra-arterial papaverine (P=.0277). Younger age (<51 years of age) was significantly associated with severity of vasospasm regarding extension on angiography (P=.0422), the need for repetitive endovascular treatment (P=.0084), persistence of transcranial Doppler ultrasound vasospasm after endovascular treatment (P=.0004), and resistance against intra-arterial papaverine (P=.0341). CONCLUSIONS: Younger age and early onset of vasospasm on transcranial Doppler ultrasound are important predictors for vasospasm severity. We recommend early and aggressive therapy in this subgroup.

Wound complications after median sternotomy: a single-centre study.

OBJECTIVES: Sternal wound complications following median sternotomy remain a challenge in cardiac surgery. Changes in both patient profile and type of operations have been observed in recent years. Therefore, we analysed current wound healing complications after median sternotomy at our centre. METHODS: All adult patients undergoing a median sternotomy between January 2009 and April 2011 were included in this retrospective analysis. Transplants and assist devices implantations were omitted. We assessed outcome, prognostic factors and microbiological results of standardized wound swabs. RESULTS: In total, 1297 patients with an average age of 67.0 ± 12.7 years were analysed. Operation types included 598 solitary coronary artery bypass grafts (CABGs), 213 solitary valve procedures, 105 CABGs with aortic valve replacement and 116 solitary aortic operations or conduit implantations. Furthermore, 255 of the remaining 265 were combined or otherwise complex procedures. Superficial healing disorders occurred in 43 patients (3.3%), while 33 (2.5%) developed deep wound complications. Six patients with sternal wound complications (7.9%) died in-hospital. In 7 patients, no pathogen was identified and the wound appeared uninfected (21% of all deep complications or 0.05% of all patients). These healing disorders were considered deep dehiscences. Patients with insulin-dependent diabetes mellitus, BMI of >40 kg/m(2) and who underwent reoperation were prone to superficial infections. Risk factors for all deep sternal wound complications were insulin-dependent diabetes mellitus, COPD and reoperation. Moreover, multivariate analysis revealed 'emergency' as an independent prognostic factor for all sternal wound complications. Microbial swabs of the sternal wound were taken in 82 of the 1297 patients (6.6%). Pathogens of the normal skin flora represented the majority of pathogens in both superficial and deep wound complications. Eight patients with deep, but only 2 patients with superficial complications suffered from polymicrobial infections. All deep polymicrobial infections involved coagulase-negative Staphylococci. CONCLUSIONS: Wound complications following median sternotomy remain a challenge to cardiac surgery. Redo and emergency operations are the most important risk factors in this contemporary series. More efforts seem mandatory to decrease this arduous morbidity and the costs of prolonged treatment.

Diagnosis of viral myocarditis by cardiac magnetic resonance and viral genome detection in peripheral blood.

In patients with acute myocarditis, viral genome can be detected in plasma and peripheral leukocytes. Its relationship with active myocardial inflammation, however, is not well understood. Myocardial edema as a feature of inflammation and myocardial necrosis or fibrosis can be frequently observed in patients with acute myocarditis by cardiovascular magnetic resonance (CMR). We assessed the association of viral genome presence in peripheral blood samples with myocardial edema and irreversible injury. We examined consecutive patients with clinically suspected myocarditis after an episode of viral illness. State-of-the-art methods were used for detecting myocardial edema and irreversible injury using CMR and viral genome applying reverse transcribed, nested polymerase chain reaction in peripheral blood samples. The specificity of viral amplification products was confirmed by automatic DNA sequencing. Of a total of 55 patients (53.5 ± 15.6 years), 21 were positive for viral genome in peripheral leukocytes. Interestingly, 18 (86%) of these patients also showed global myocardial edema, as compared to only 7/34 (21%) without PCR evidence for viral genome. The overall agreement between CMR criteria for edema and viral PCR was 84%. In contrast, there was no significant relationship of viral genome presence with myocardial necrosis or scars. In patients with clinically suspected myocarditis, myocardial edema but not irreversible myocardial injury is associated with the presence of viral genome in peripheral blood.

Randomized controlled single-center trial comparing pancreatogastrostomy versus pancreaticojejunostomy after partial pancreatoduodenectomy.

BACKGROUND: The aim of this single-center randomized trial was to compare the perioperative outcome of pancreatoduodenectomy with pancreatogastrostomy (PG) vs pancreaticojejunostomy (PJ). METHODS: Randomization was done intraoperatively. PG was performed via anterior and posterior gastrotomy with pursestring and inverting seromuscular suture; control intervention was PJ with duct-mucosa anastomosis. The primary endpoint was postoperative pancreatic fistula (POPF). RESULTS: From 2006 to 2011, n = 268 patients were screened and n = 116 were randomized to n = 59 PG and n = 57 PJ. There was no statistically significant difference regarding the primary endpoint (PG vs PJ, 10 % vs 12 %, p = 0.775). The subgroup of high-risk patients with a soft pancreas had a non-significantly lower pancreatic fistula rate with PG (PG vs PJ, 14 vs 24 %, p = 0.352). Analysis of secondary endpoints demonstrated a shorter operation time (404 vs 443 min, p = 0.005) and reduced hospital stay for PG (15 vs 17 days, p = 0.155). Delayed gastric emptying (DGE; PG vs PJ, 27 vs 17 %, p = 0.246) and intraluminal bleeding (PG vs PJ, 7 vs 2 %, p = 0.364) were more frequent with PG. Mortality was low in both groups (<2 %). CONCLUSIONS: Our randomized controlled trial shows no difference between PG and PJ as reconstruction techniques after partial pancreatoduodenectomy. POPF rate, DGE, and bleeding were not statistically different. Operation time was significantly shorter in the PG group.

Novel single-chain antibody-targeted microbubbles for molecular ultrasound imaging of thrombosis: validation of a unique noninvasive method for rapid and sensitive detection of thrombi and monitoring of success or failure of thrombolysis in mice.

BACKGROUND: Molecular imaging is a fast emerging technology allowing noninvasive detection of vascular pathologies. However, imaging modalities offering high resolution currently do not allow real-time imaging. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) selectively targeted to activated platelets would offer high-resolution, real-time molecular imaging of evolving and dissolving arterial thrombi. METHODS AND RESULTS: Lipid-shell based gas-filled MBs were conjugated to either a single-chain antibody specific for activated glycoprotein IIb/IIIa via binding to a Ligand-Induced Binding Site (LIBS-MBs) or a nonspecific single-chain antibody (control MBs). Successful conjugation was assessed in flow cytometry and immunofluorescence double staining. LIBS-MBs but not control MBs strongly adhered to both immobilized activated platelets and microthrombi under flow. Thrombi induced in carotid arteries of C57Bl6 mice in vivo by ferric chloride injury were then assessed with ultrasound before and 20 minutes after MB injection through the use of gray-scale area intensity measurement. Gray-scale units converted to decibels demonstrated a significant increase after LIBS-MB but not after control MB injection (9.55±1.7 versus 1.46±1.3 dB; P<0.01). Furthermore, after thrombolysis with urokinase, LIBS-MB ultrasound imaging allows monitoring of the reduction of thrombus size (P<0.001). CONCLUSION: We demonstrate that glycoprotein IIb/IIIa-targeted MBs specifically bind to activated platelets in vitro and allow real-time molecular imaging of acute arterial thrombosis and monitoring of the success or failure of pharmacological thrombolysis in vivo.

Evidence of myocardial edema in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Nonischemic dilated cardiomyopathy (DCM) is associated with high mortality and morbidity. Cardiovascular magnetic resonance allows for the noninvasive assessment of function, morphology, and myocardial edema. Activation of inflammatory pathways may play an important role in the etiology of chronic DCM and may also be involved in the disease progression. HYPOTHESIS: The purpose of our study was to assess the incidence of myocardial edema as a marker for myocardial inflammation in patients with nonischemic DCM. METHODS: We examined 31 consecutive patients ( mean age, 57 ± 12 years) with idiopathic DCM. Results were compared with 39 controls matched for gender and age (mean age, 53 ± 13 years). Parameters of left ventricular function and volumes, and electrocardiogram-triggered, T2-weighted, fast spin echo triple inversion recovery sequences were applied in all patients and controls. Variables between patients and controls were compared using t tests for quantitative and χ2 tests for categorical variables. RESULTS: Ejection fraction (EF) was 40.3 ± 7.8% in patients and 62.6 ± 5.0% in controls (P < 0.0001). In T2-weighted images, patients with DCM had a significantly higher normalized global signal intensity ratio compared to controls (2.2 ± 0.6 and 1.8 ± 0.3, respectively, P = 0.0006), consistent with global myocardial edema. There was a significant but moderate negative correlation between signal intensity ratio in T2-weighted images and EF (-0.39, P < 0.001). CONCLUSIONS: Evidence shows that myocardial edema is associated with idiopathic nonischemic DCM. Further studies are needed to assess the clinical and prognostic impact of these findings.

Risk factors and complications following percutaneous endoscopic gastrostomy: a case series of 1041 patients.

BACKGROUND: Most studies exclude patients with severe coagulation disorders or those taking anticoagulants when evaluating the outcomes of percutaneous endoscopic gastrostomy (PEG). OBJECTIVE: To investigate complications and risk factors of PEG in a large clinical series including patients undergoing antiplatelet and anticoagulant therapy. METHODS: During a six-year period, 1057 patients referred for PEG placement were prospectively audited for clinical outcome. Exclusion criteria and follow-up care were defined. Complications were defined as minor or severe. Uni- and multivariate analyses were used to evaluate 14 risk factors. No standardized antibiotic prophylaxis was given. RESULTS: A total of 1041 patients (66% male, 34% female) with the following conditions underwent PEG: neurogenic dysphagia (n=450), cancer (n=385) and others (n=206). No anticoagulants were administered to 351 patients, thrombosis prophylaxis was given to 348 while full therapeutic anticoagulation was received by 313. No increased bleeding risk was associated with patients who had above-normal international normalized ratio values (OR 0.79 [95% CI 0.08 to 7.64]; P=1.00). The total infection rate was 20.5% in patients with malignant disease, and 5.5% in those with nonmalignant disease. Severe complications occurred in 19 patients (bleeding 0.5%, peritonitis 1.3%). Cirrhosis (OR 2.91 [95% CI 1.31 to 6.54]; P=0.008), cancer (OR 2.34 [95% CI 1.33 to 4.12]; P=0.003) and radiation therapy (OR 2.34 [95% CI 1.35 to 4.05]; P=0.002) were significant predictors of post-PEG infection. The 30-day mortality rate was 5.8%. There were no procedure-related deaths. CONCLUSIONS: Cancer, cirrhosis and radiation therapy were predictors of infection. Post-PEG bleeding and other complications were rare events. Collectively, the data suggested that patients taking concurrent anticoagulants had no elevated risk of post-PEG bleeding.

Palliative cancer care: an epidemiologic study.

PURPOSE: To analyze the need for palliative care in hospital patients who have cancer. Palliative care is an essential component of comprehensive cancer care and identification of palliative care needs (PCNs) of patients with cancer is a topic that has not been thoroughly studied. PATIENTS AND METHODS: Data were collected prospectively from inpatients of University Medical Center Freiburg in Freiburg, Germany, with 982 hospital beds included in the study. During the observation period of 17 months, each patient discharged from a hospital ward was screened by surveying the treating physician who was responsible for dismissal about patients' PCNs based on the WHO 1990 definition of palliative care. To complete obligatory electronic discharge management, a modified dismissal form asking to classify the patient as having PCN "yes/no" had to be filled out for each patient discharged. RESULTS: The response rate was 96% with data for 39,849 patients that could be analyzed. A total of 6.9% of all hospital patients and 9.1% of patients older than age 65 years were considered to have PCNs. Of the 2,757 patients with PCNs, 67% (n = 1,836) had cancer. Among the 11,584 patients with cancer, 15.8% were classified as having PCNs. PCNs were particularly high in patients with head and neck cancer (28.3%), malignant melanoma (26.0%), and brain tumors (18.2%). Suffering from cancer increases the probability of developing PCNs by a factor of 3.63 (95% CI, 3.27 to 4.04). For patients with metastatic cancer, the risk of developing PCNs is increased 12-fold (odds ratio, 12.27; 95% CI, 11.07 to 13.60). CONCLUSION: Structures to provide palliative care for patients with cancer are needed.

Improvement of exhausted cerebral vasoreactivity in carotid occlusion: benefit of statins?

In internal carotid artery occlusion (ICAO), a spontaneous increase of cerebral vasoreactivity (CVR) may occur over time. Statins are known to increase CVR. We analyzed the influence of statin treatment and other cofactors on CVR improvement in patients with ICAO. Sixty-six patients with ICAO were reexamined after 15 ± 6 months. CVR in both middle cerebral arteries was assessed by transcranial Doppler and inhalation of 7% CO(2). Pre-defined cut-off values were used to define exhausted CVR. Cofactors analyzed were: age, sex, hypertension, diabetes, statin treatment, degree of contralateral stenosis, quality of intracranial collateral flow, duration of ICAO. Mean CVR did not differ between the two studies. Twenty patients had exhausted CVR at baseline, 11 of them improved above the cut-off at follow-up (55%). Factors significantly associated with this improvement were good collateral pattern at baseline (p = 0.0065) and statin treatment (p = 0.0179). Odds ratios for improving CVR were 36.0 [95% CI 2.7-476.3] for good collateral flow and 20.0 [95% CI 1.7-238.6] for statin treatment. In conclusion, exhausted CVR frequently improves during the course of ICAO. Good collateral function and statin treatment are significantly associated with improving CVR.

Success of arterial revascularization determined by contrast ultrasound muscle perfusion imaging.

BACKGROUND: In the early postoperative evaluation of the success of arterial revascularization, ankle-brachial index (ABI) and other noninvasive tests lack reliability, especially in patients with incompressible arteries or local edema. Contrast-enhanced ultrasound (CEUS) imaging of limb muscle perfusion may be an alternative to standard tests if it detects treatment success reliably. METHODS: We compared a simplified CEUS method with clinical staging, pulse volume recording (PVR), and ABI in patients with lifestyle-limiting peripheral arterial disease undergoing revascularization by percutaneous transluminal angioplasty (PTA) or bypass surgery. Patients underwent staging, PVR, ABI, and CEUS before, directly after, and 3 to 5 months after successful PTA (n = 20) or successful bypass grafting (n = 14). For CEUS, contrast agent was injected into an antecubital vein, and the time from beginning to peak intensity of contrast enhancement (TTP) in the calf muscle was measured. RESULTS: Successful revascularization by both PTA and bypass was associated with a significant improvement in staging, PVR, ABI, and TTP directly after intervention and at follow-up. Median ABI increased from 0.60 to 0.85 (P = .001) after PTA and from 0.36 to 0.76 (P = .003) after bypass surgery. Median TTP decreased from 45 seconds to 24 seconds (P = .015) and from 30 seconds to 27 seconds (P = .041), respectively. McNemar analysis revealed unidirectional changes in both ABI and TTP (P = .625 after PTA and P = 1.000 after bypass surgery), and equivalence analysis showed 95% confidence intervals within clinical indifference, indicating that TTP was equivalent to standard tests in detecting successful revascularization. CONCLUSIONS: Contrast ultrasound perfusion imaging of calf muscle after arterial revascularization may be a valuable alternative to standard noninvasive tests such as ABI or PVR to determine the success of an arterial revascularization.

Severe endothelial injury and subsequent repair in patients after successful cardiopulmonary resuscitation.

INTRODUCTION: Ischemia and reperfusion after cardiopulmonary resuscitation (CPR) induce endothelial activation and systemic inflammatory response, resulting in post-resuscitation disease. In this study we analyzed direct markers of endothelial injury, circulating endothelial cells (CECs) and endothelial microparticles (EMPs), and endothelial progenitor cells (EPCs) as a marker of endothelial repair in patients after CPR. METHODS: First we investigated endothelial injury in 40 patients after CPR, 30 controls with stable coronary artery disease (CAD), and 9 healthy subjects, who were included to measure CECs and EMPs. In a subsequent study, endothelial repair was assessed by EPC measurement in 15 CPR, 9 CAD, and 5 healthy subjects. Blood samples were drawn immediately and 24 hours after ROSC and analyzed by flow cytometry. For all statistical analyses P < 0.05 was considered significant. RESULTS: There was a massive rise in CEC count in resuscitated patients compared to CAD (4,494.1 +/- 1,246 versus 312.7 +/- 41 cells/mL; P < 0.001) and healthy patients (47.5 +/- 3.7 cells/mL; P < 0.0005). Patients after prolonged CPR (>or=30 min) showed elevated CECs compared to those resuscitated for <30 min (6,216.6 +/- 2,057 versus 2,340.9 +/- 703.5 cells/mL; P = 0.13/ns). There was a significant positive correlation of CEC count with duration of CPR (R2= 0.84; P < 0.01). EMPs were higher immediately after CPR compared to controls (31.2 +/- 5.8 versus 19.7 +/- 2.4 events/microL; P = 0.12 (CAD); versus 15.0 +/- 5.2 events/microL; P = 0.07 (healthy)) but did not reach significance until 24 hours after CPR (69.1 +/- 12.4 versus 22.0 +/- 3.0 events/microL; P < 0.005 (CAD); versus 15.4 +/- 4.4 events/microL; P < 0.001 (healthy)). EPCs were significantly elevated in patients on the second day after CPR compared to CAD (1.16 +/- 0.41 versus 0.02 +/- 0.01% of lymphocytes; P < 0.005) and healthy (0.04 +/- 0.01; P < 0.005). CONCLUSIONS: In the present study we provide evidence for a severe endothelial damage after successful CPR. Our results point to an ongoing process of endothelial injury, paralleled by a subsequent endothelial regeneration 24 hours after resuscitation.

Enhanced microparticles in ventricular assist device patients predict platelet, leukocyte and endothelial cell activation.

Platelet dysfunction followed by thromboembolic as well as bleeding complications are severe events in patients with ventricular assist devices (VADs). Microparticles (MP) are cell vesicles with inflammatory and coagulatory potency that are released by cells during activation and can be used as specific cell activation markers. The aim of the study was to establish MP as surrogate markers for platelet, leukocyte and endothelial activation in VAD patients predicting platelet activation and vascular inflammation. Therefore, MP from platelet, leukocyte and endothelial origin were measured in 12 patients with VAD and compared to controls. VAD patients had significantly increased levels of platelet microparticles (PMP) (VAD 1705+/-1100 cpm vs. co: 527+/-238 cpm, P=0.002), leukocyte microparticles (LMP) (VAD 43+/-16 cpm vs. co: 18+/-8 cpm, P<0.001) and endothelial microparticles (EMP) (VAD 135+/-66 cpm vs. co: 46+/-23 cpm, P<0.001) indicating enhanced vascular inflammation and pro-coagulation. Furthermore, LMP correlated well to EMP suggesting that LMP induce endothelial cell dysfunction. In conclusion, VAD patients suffer from enhanced platelet, leukocyte and endothelial activation that can be easily quantified by measuring PMP, LMP and EMP and that may help to estimate the thrombotic risk and contribute to avoid ischemic but also bleeding complications.

Complex plaques in the proximal descending aorta: an underestimated embolic source of stroke.

BACKGROUND AND PURPOSE: To investigate the incidence of retrograde flow from complex plaques (> or =4-mm-thick, ulcerated, or superimposed thrombi) of the descending aorta (DAo) and its potential role in embolic stroke. METHODS: Ninety-four consecutive acute stroke patients with aortic plaques > or =3-mm-thick in transesophageal echocardiography were prospectively included. MRI was performed to localize complex plaques and to measure time-resolved 3-dimensional blood flow within the aorta. Three-dimensional visualization was used to evaluate if diastolic retrograde flow connected plaque location with the outlet of the left subclavian artery, left common carotid artery, or brachiocephalic trunk. Complex DAo plaques were considered an embolic source if retrograde flow reached a supra-aortic vessel that supplied the territory of visible acute and embolic retinal or cerebral infarction. RESULTS: Only decreasing heart rate was correlated (P<0.02) with increasing flow reversal to the aortic arch. Retrograde flow from complex DAo plaques reached the left subclavian artery in 55 (58.5%), the left common carotid artery in 23 (24.5%), and the brachiocephalic trunk in 13 patients (13.8%). Based on routine diagnostics and MRI of the ascending aorta/aortic arch, stroke etiology was determined in 57 and cryptogenic in 37 patients. Potential embolization from DAo plaques was then identified in 19 of 57 patients (33.3%) with determined and in 9 of 37 patients (24.3%) with cryptogenic stroke. CONCLUSIONS: Retrograde flow from complex DAo plaques was frequent in both determined and cryptogenic stroke and could explain embolism to all brain territories. These findings suggest that complex DAo plaques should be considered a new source of stroke.