Abstract Introduction The high shear rates induced by left ventricular assist devices cause acquired von Willebrand disease (aVWD). We hypothesised that an ex vivo model could be established to study ...whether mechanical shear stress alone causes aVWD or whether this process depends also on the VWF cleavage protein ADAMTS-13 and on platelets. Materials and methods Healthy volunteers and two patients with congenital ADAMTS-13 deficiency donated blood. In vitro closed extracorporeal circuits were established using medically approved left ventricular assist devices (LVAD). VWF multimers were quantified by gel electrophoresis; VWF antigen, ristocetin cofactor activity (VWF:RCo), ADAMTS-13 levels and platelet function were assessed. Results The high shear stress in the extracorporeal circulation rapidly decreased VWF:RCo and thereby the VWF:RCo/VWF:Ag ratio by 47% (p < 0.01) to pathologically low values. Concomitantly, high molecular weight multimers (HMWM) decreased: up to 14–15 mers were visible on the gels at baseline, which were reduced by a maximum of 6–7 mers, corresponding to an average 68% lower densitometry signal of HMWM (p < 0.001). This was accompanied by marked reduction of aggregation by various agonists (p < 0.005). In contrast, the two patients with congenital thrombocytopenic purpura with virtually complete deficiency of ADAMTS-13 activity had only a minimal or no decrease in multimers (p < 0.005 vs. healthy controls). Similarly, no or minimal depletion of large multimers occurred, when normal plasma circulated without platelets. Conclusion An in vitro model for LVAD associated aVWD demonstrated that ADAMTS-13 and platelets contribute to the depletion of HMWM of VWF.
Background and objective
Microcirculatory changes contribute to clinical symptoms and disease progression in chronic heart failure (CHF). A depression of coronary flow reserve is associated with a ...lower myocardial capillary density in biopsies. We hypothesized that changes in cardiac microcirculation might also be reflected by a systemic reduction in capillaries and visualized by sublingual videomicroscopy. The aim was to study in vivo capillary density and glycocalyx dimensions in patients with CHF vs healthy controls.
Methods
Fifty patients with ischaemic and nonischaemic CHF and standard treatment were compared to 35 healthy age‐matched subjects in a prospective cross‐sectional study. Sublingual microcirculation was visualized using a sidestream darkfield videomicroscope. Functional and perfused total capillary densities were compared between patients and controls. A reduced glycocalyx thickness was measured by an increased perfused boundary region (PBR).
Results
Median functional and total perfused capillary densities were 30% and 45% lower in patients with CHF (both P < .001). Intake of oral vitamin K antagonists was associated with significantly lower capillary densities (P < .05), but not independent of NT‐proBNP. Dimensions of the glycocalyx were marginally lower in CHF patients than in healthy controls (<7% difference). However, PBR correlated significantly with inflammation markers (fibrinogen: r = .58; C‐reactive protein: r = .42), platelet counts (r = .36) and inversely with measures of liver/renal function such as bilirubin (r = −.38) or estimated glomerular filtration rate (r = −.34) in CHF patients.
Conclusion
CHF patients have got a markedly lower functional and total perfused capillary density in sublingual microvasculature when compared to controls, indicating a systemic decrease in microcirculation.
OBJECTIVES
Interagency Registry for Mechanical Assisted Circulatory Support (INTERMACS) Level I patients have the highest early mortality after ventricular assist device (VAD) implantation. This is ...determined by the exposure of patients in shock with acutely damaged end-organs and high catecholamine support to a significant surgical trauma. We report our experience with a bridge-to-bridge concept consisting of initial veno-arterial extracorporeal life support (ECLS) and deferral of VAD implantation to recovery of end-organ function in INTERMACS Level I patients.
METHODS
We reviewed the concept of initial ECLS implantation and deferral of VAD implantation to end-organ recovery in 22 consecutive patients (mean age 54 ± 14 years; 72.2% males; 50% ischemic cardiomyopathy; 100% INTERMACS Level I; 18.2% Heartmate II, 68.2% Heartware HVAD, 4.5% Heartware BiVAD, 9.1% DeBakey LVAD) receiving a VAD for refractory cardiogenic shock between June 2004 and February 2013. Study endpoints were end-organ recovery during ECLS and survival.
RESULTS
ECLS significantly improved renal (creatinine 1.86 ± 0.91 vs 1.32 ± 0.52 mg/dl, P = 0.02), hepatic (aspartate aminotransferase 1426 ± 2176 vs 277 ± 259 U/l, P = 0.04; alanine aminotransferase 982 ± 1466 vs 357 ± 447 U/l, P = 0.04) and pulmonary functions (fraction of inspired oxygen 52 ± 18 vs 26 ± 23%, P < 0.01; positive end-expiratory pressure 7 ± 3 vs 5 ± 4 mbar, P = 0.02) over a period of 8 ± 7 days. Catecholamines could be reduced during ECLS (levosimendan 0.056 ± 0.085 vs 0.010 ± 0.032 μg/kg/min, P = 0.06; dobutamine 4.362 ± 5.268 vs 0.056 ± 0.097 μg/kg/min, P = 0.06; noradrenaline 0.408 ± 0.355 vs 0.056 ± 0.097 μg/kg/min, P < 0.01). Thirty-day and in-hospital mortality after VAD implantation were 4.5 and 9.1%, respectively, and 1-year survival was 86.4%.
CONCLUSIONS
Preoperative patient optimization using ECLS improves outcomes of INTERMACS Level I patients receiving a permanent VAD.
Background Fibroblast growth factor 23 (FGF-23) is crucial in regulating phosphate and vitamin D metabolism and is moreover associated with an increased cardiovascular risk. The specific objective of ...this study was to investigate the influence of FGF-23 on cardiovascular outcomes, including hospitalization for heart failure (HHF), postoperative atrial fibrillation, and cardiovascular death, in an unselected patient population after cardiac surgery. Methods and Results Patients undergoing elective coronary artery bypass graft and/or cardiac valve surgery were prospectively enrolled. FGF-23 blood plasma concentrations were assessed before surgery. A composite of cardiovascular death/HHF was chosen as primary end point. A total of 451 patients (median age 70 years; 28.8% female) were included in the present analysis and followed over a median of 3.9 years. Individuals with higher FGF-23 quartiles showed elevated incidence rates of the composite of cardiovascular death/HHF (quartile 1, 7.1%; quartile 2, 8.6%; quartile 3, 15.1%; and quartile 4, 34.3%). After multivariable adjustment, FGF-23 modeled as a continuous variable (adjusted hazard ratio for a 1-unit increase in standardized log-transformed biomarker, 1.82 95% CI, 1.34-2.46) as well as using predefined risk groups and quartiles remained independently associated with the risk of cardiovascular death/HHF and the secondary outcomes, including postoperative atrial fibrillation. Reclassification analysis indicated that the addition of FGF-23 to N-terminal pro-B-type natriuretic peptide provides a significant improvement in risk discrimination (net reclassification improvement at the event rate, 0.58 95% CI, 0.34-0.81;
<0.001; integrated discrimination increment, 0.03 95% CI, 0.01-0.05;
<0.001). Conclusions FGF-23 is an independent predictor of cardiovascular death/HHF and postoperative atrial fibrillation in individuals undergoing cardiac surgery. Considering an individualized risk assessment, routine preoperative FGF-23 evaluation may improve detection of high-risk patients.
The highly β1-selective beta-blocker Landiolol is known to facilitate efficient and safe rate control in non-compensatory tachycardia or dysrhythmia when administered continuously. However, efficacy ...and safety data of the also-available bolus formulation in critically ill patients are scarce.
We conducted a retrospective cross-sectional study on a real-life cohort of critical care patients, who had been treated with push-dose Landiolol due to sudden-onset non-compensatory supraventricular tachycardia. Continuous hemodynamic data had been acquired via invasive blood pressure monitoring.
Thirty patients and 49 bolus applications were analyzed. Successful heart rate control was accomplished in 20 (41%) cases, rhythm control was achieved in 13 (27%) episodes, and 16 (33%) applications showed no effect. Overall, the heart rate was significantly lower (145 (130-150) vs. 105 (100-125) bpm,
< 0.001) in a 90 min post-application observational period in all subgroups. The median changes in blood pressure after the bolus application did not reach clinical significance. Compared with the ventilation settings before the bolus application, the respiratory settings including the required FiO
after the bolus application did not differ significantly. No serious adverse events were seen.
Push-dose Landiolol was safe and effective in critically ill ICU patients. No clinically relevant impact on blood pressure was noted.
Background Thromboembolic and bleeding complications in outpatients with a left ventricular assist device are common and can be detrimental. A meticulous balance between anticoagulant and ...procoagulant factors is therefore crucial. However, in contrast to routinely performed plasmatic coagulation tests, platelet function is hardly ever monitored although recent reports indicated platelet dysfunction. We therefore differentially evaluated platelet function with four commonly used point-of-care devices. Methods In a cross-sectional design platelet function was assessed in 12 outpatients and 12 healthy matched volunteers using thrombelastography platelet mapping, thromboelastometry, platelet function analyzer, and a new whole blood aggregometer (Multiplate). Results Phenprocoumon produced an international normalized ratio of 3.5. It was associated with a twofold prolongation in the thromboelastometry clotting time ( p < 0.001). Platelet function under high shear was severely compromised: collagen adenosine diphosphate closure times were 2.5-fold longer in patients than in volunteers ( p < 0.001), and 50% of patients had maximal collagen adenosine diphosphate closure time values. Although antigen levels of von Willebrand factor were 80% higher in patients ( p < 0.001), von Willebrand factor–ristocetin was subnormal in 5 of 12 patients. Ristocetin-induced aggregation was also threefold higher in volunteers ( p < 0.001), indicating an additional functional defect of platelets affecting the glycoprotein Ib–von Willebrand factor axis. The von Willebrand factor multimer pattern in patients also appeared abnormal. Conclusions Multimodal antiplatelet monitoring showed markedly impaired platelet function in patients with a left ventricular assist device. Platelet dysfunction under high shear rates and abnormal ristocetin-induced aggregation is only partly attributable to low von Willebrand factor activity. These findings resemble the acquired von Willebrand syndrome that is associated with microaggregate formation and enhanced bleeding.
Background. The use of left ventricular assist device (LVAD) has increased considerably over the past decade; however, there is limited literature to assist in patient selection and monitoring. The ...frequency of adverse events remains high. We examined the early expression of circulating soluble ST2 (sST2), a biomarker with immunosuppressive and profibrotic activity, and assessed the risk of death at 1 year in patients receiving LVAD implant. Methods. We prospectively enrolled 20 heart failure patients and measured sST2, IL-33, and IL-6 serum concentrations over three weeks after LVAD implantation. We compared the kinetics of IL-6, sST2, and IL-33 release in survivors with those of nonsurvivors using mixed model two-way analysis of variance for repeated measures. We also collected data on hemodynamic parameters (i.e., cardiac output) and frequency of infections during the hospital stay. Results. LVAD therapy led to an immediate and significant improvement of the hemodynamic parameters in 1-year survivors and nonsurvivors alike. The 1-year survival rate was 65%. IL-6 concentrations showed a significant (p=0.03) peak at admission to the intensive care unit following LVAD implantation, whereas sST2 levels were massively increased (p<0.0003) on day 1. While 1-year survivors had persistently lower sST2 values compared to nonsurvivors during the first 3 weeks after LVAD implantation (p=0.012), no differences were observed in the temporal pattern of IL-6 or IL-33. The odds of detecting Candida species in the bronchoalveolar lavage fluid were 14 times higher in nonsurvivors than in survivors (OR 13.7, CI 1.4-127, p=0.02). Conclusion. In patients implanted with LVAD, circulating sST2 levels and frequency of Candida colonisation were associated with higher mortality. Awareness of this early immune response can guide physicians in risk-benefit analysis.
Heart failure patients are frequently on coagulation-active medications before LVAD implantation and perioperative bleeding is a frequent complication after left ventricular assist device (LVAD) ...implantation. The role of point-of-care coagulation tests in assessing bleeding risk for LVAD implantation and the early postoperative time course of these tests is not well established.
We prospectively enrolled 25 patients with terminal heart failure undergoing LVAD implantation. Study related TRAP-, ASPI- and ADP- tests of Multiplate
platelet aggregometry, ROTEM
rotational thromboelastometry (INTEM, EXTEM, FIBTEM), thrombin generation assay and conventional laboratory studies were measured at 11 predefined time-points during the first 21 postoperative days. We examined if preoperative TRAP-, ASPI-, ADP- and ROTEM values are correlated with estimated total blood loss (primary outcome parameter) during the first 21 days after LVAD implantation and compared the baseline values of these measurements between patients with a bleeding event to those without. We performed Spearman's correlation and non-parametric tests for paired and non-paired comparisons.
7 out of 25 (28%) patients experienced a bleeding event of which 4 required surgical revision. Of the preoperatively performed measurements the TRAP test Spearman's Rho (ρ) = -0.5,
= 0.01, INTEM CFT (ρ = 0.72,
< 0.001), INTEM alpha (-0.7,
< 0.001), EXTEM MCF (ρ = -0.63;
< 0.001), EXTEM alpha (ρ = -0.67;
< 0.001), FIBTEM MCF (ρ = -0.41;
= 0.042), Fibrinogen (Clauss) (ρ = -0.5;
= 0.011), Anti-thrombin activity (ρ = -0.49;
= 0.013) and platelet count (ρ = -0.42;
= 0.034) were significantly correlated to total blood loss. Patients undergoing a surgical bleeding revision had significantly reduced values in TRAP-31.5 IQR (17.25-43.5U) vs. 69 IQR (52.5-87U);
= 0.004, ASPI-16.5 IQR (5.5-35.7U) vs. 39 IQR (24.5-62.5U);
= 0.038, ADP-30 IQR (22-69U) vs. 12.5 IQR (8.7-21.5U);
= 0.01, EXTEM MCF-63 IQR (57.7-63.7) vs. 67 IQR (65-75.5);
= 0.019 and EXTEM alpha 74 IQR (68.75-74) vs. 79 IQR (78-80.5);
= 0.002 values before LVAD implantation.
Multiplate
and ROTEM
measurements before LVAD implantation may identify LVAD candidates with platelet dysfunction and alterations of the primary hemostasis and could guide anesthetists and intensive care practitioners in bleeding risk stratification and in the perioperative clinical management.
Pseudothrombocytopenia (PTCP) is an in vitro phenomenon of low platelet count caused by the agglutination of platelets, leading to false low platelet counts in automated cell counting. Typically, ...ethylenediaminetetraacetic acid (EDTA) mediates this platelet clumping. PTCP has little clinical significance, but misdiagnosis may lead to unnecessary diagnostic tests and treatment. In this case report, we present a 65-year-old Caucasian female suffering from multiple complications during and after cardiac surgery. During her postoperative stay at the ICU, she was diagnosed with thrombocytopenia and an inadequate response to platelet supplementation.
Extracorporeal membrane oxygenation (ECMO) is often used in the management of COVID-19-related severe respiratory failure. We report the first case of a patient with COVID-19-related ARDS on ECMO ...support who developed symptoms of heparin-induced thrombocytopenia (HIT) in the absence of heparin therapy. A low platelet count of 61 G/L was accompanied by the presence of circulating HIT antibodies 12 days after ECMO initiation. Replacement of the ECMO system including cannulas resulted in the normalization of the platelet count. However, the clinical situation did not improve, and the patient died 9 days later. Careful consideration of anticoagulant therapy and ECMO circuit, as well as routine HIT antibody testing, may prevent a fatal course in ECMO-supported COVID-19 patients.
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