Superior outcomes with Argatroban for heparin-induced thrombocytopenia: a Bayesian network meta-analysis.

Background Argatroban, lepirudin, desirudin, bivalirudin, and danaparoid are commonly used to manage heparin-induced thrombocytopenia related complications. However, the most suitable drug for this condition still remains controversial. Aim of the review This Bayesian network meta-analysis study compared the most common anticoagulant drugs used in the management of heparin-induced thrombocytopenia. Method All clinical trials comparing two or more anticoagulant therapies for suspected or confirmed heparin-induced thrombocytopenia were considered for inclusion. Studies concerning the use of heparins or oral anticoagulants were not considered. Data concerning hospitalisation length, thromboembolic, major, and minor haemorrhagic events, and mortality rate were collected. The network analyses were made through the STATA routine for Bayesian hierarchical random-effects model analysis with standardised mean difference (SMD) and log odd ratio (LOR) effect measures. Results Data from a total of 4338 patients were analysed. The overall mean age was 62.31 ± 6.6 years old. Hospitalization length was considerably shorter in favour of the argatroban group (SMD: - 1.70). Argatroban evidenced the lowest rate of major (LOR: - 1.51) and minor (LOR: - 0.57) haemorrhagic events. Argatroban demonstrated the lowest rate of thromboembolic events (LOR: 0.62), and mortality rate (LOR: - 1.16). Conclusion Argatroban performed better overall for selected patients with HIT. Argatroban demonstrated the shortest hospitalization, and lowest rate of haemorrhages, thromboembolisms, and mortality compared to bivalirudin, lepirudin, desirudin, and danaparoid.

Transesophageal echocardiography in swine: evaluation of left and right ventricular structure, function and myocardial work.

This study aimed to determine standard left (LV) and right ventricular (RV) transesophageal echocardiographic (TEE) measurements in swine. Additionally, global myocardial work index (GWI) was estimated using pressure-strain loops (PSL). A comprehensive TEE examination was conducted in ten anesthetized, intubated and mechanically ventilated healthy female German landrace swine, weighing 44 to 57 kg. For GWI calculation, we performed LV and RV segmental strain analysis and used invasively measured LV and RV pressure to obtain PSL. The GWI and further myocardial work indices were calculated from the area of the PSL using commercially available software. Furthermore, hemodynamic measurements were obtained using indwelling catheters. We obtained complete standardized baseline values for left and right ventricular dimensions and function. Biplane LV ejection fraction was 63 ± 7 % and the LV end-diastolic volume was 70.5 ± 5.9 ml. Tissue Doppler estimated peak tricuspid annular systolic velocity was 13.1 ± 1.8 cm/s. The Doppler estimated LV and RV stroke volume index were 75.6 ± 7.2 ml/m2 and 76.7 ± 7.8 ml/m2 respectively. Pulsed wave Doppler derived cardiac output correlated well with cardiac output estimated using the thermodilution method (7.0 ± 1.2 l/min vs. 7.0 ± 1.1 l/min, r = 0.812, p = 0.004). The LV global longitudinal strain was -21.3 ± 3.9 % and the RV global longitudinal strain was -15.4 ± 2.5 %. LV GWI was 1885(1281-2121) mmHg*% and 297 ± 62 mmHg*% for the RV. LV global myocardial work efficiency was 82.6 ± 4 % and 83(72-88) % for the RV. TEE offers sufficient morphological, functional and hemodynamic assessment of the heart in swine. Myocardial contractility and mechanics can be reliably evaluated with the non-invasive GWI derived from echocardiography without additional invasive measures.

Prognostic factors for patients with heparin-induced thrombocytopenia: a systematic review.

Background  Little is known with regards to the prognostic factors for patients with suspected or diagnosed Heparin-Induced Thromobocytopenia (HIT). The role of patient and therapy characteristics may play a role in predicting the outcome. Aim of the review To investigate the role of patient and therapy characteristics as potential prognostic factors for HIT-related complications (haemorrhagic and thromboembolic events), and mortality. Method The present systematic review was conducted according to the PRISMA statement. In September 2020, the main online databases were accessed: Pubmed, EMBASE, Scopus, Google Scholar. All the clinical trials concerning the management of patients with suspected or confirmed HIT were eligible. Studies evaluating the use of oral anticoagulants (e.g. vitamin K antagonists, Apixaban) were not considered, along with those comparing the use of heparin. For pairwise correlation, the Pearson Product-Moment Correlation Coefficient (r) was used. The final effect was evaluated according to the Cauchy-Schwarz inequality.Results Data from 33 clinical studies (4338 patients) were retrieved. The overall mean age was 62.3 ± 6.6 years old. Patients with HIT-related thromboembolism at the moment of diagnosis were associated with greater rate of haemorrhages (P > 0.0001), thromboembolism (P > 0.0001) and mortality (P = 0.001). Patients with more comorbidities at diagnosis were associated with a greater risk of haemorrhages (P = 0.07), thromboembolism (P = 0.002) and mortality (P = 0.002). Patients with longer duration of the therapy were associated with lower rate of mortality (P = 0.04). ConclusionsPatient comorbidities, presence of HIT-related thromboembolism on admission and shorter anticoagulant therapy were found to be negative prognostic factors. Thrombocythemia on admission, patients age and gender did not influence the overall outcome.

Levosimendan reduces segmental pulmonary vascular resistance in isolated perfused rat lungs and relaxes human pulmonary vessels.

INTRODUCTION: Levosimendan is approved for acute heart failure. Within this context, pulmonary hypertension represents a frequent co-morbidity. Hence, the effects of levosimendan on segmental pulmonary vascular resistance (PVR) are relevant. So far, this issue has been not studied. Beyond that the relaxant effects of levosimendan in human pulmonary vessel are unknown. We addressed these topics in rats' isolated perfused lungs (IPL) and human precision-cut lung slices (PCLS). MATERIAL AND METHODS: In IPL, levosimendan (10 µM) was perfused in untreated and endothelin-1 pre-contracted lungs. The pulmonary arterial pressure (PPA) was continuously recorded and the capillary pressure (Pcap) was determined by the double-occlusion method. Thereafter, segmental PVR, expressed as precapillary (Rpre) and postcapillary resistance (Rpost) and PVR were calculated. Human PCLS were prepared from patients undergoing lobectomy. Levosimendan-induced relaxation was studied in naïve and endothelin-1 pre-contracted PAs and PVs. In endothelin-1 pre-contracted PAs, the role of K+-channels was studied by inhibition of KATP-channels (glibenclamide), BKCa2+-channels (iberiotoxin) and Kv-channels (4-aminopyridine). All changes of the vascular tone were measured by videomicroscopy. In addition, the increase of cAMP/GMP due to levosimendan was measured by ELISA. RESULTS: Levosimendan did not relax untreated lungs or naïve PAs and PVs. In IPL, levosimendan attenuated the endothelin-1 induced increase of PPA, PVR, Rpre and Rpost. In human PCLS, levosimendan relaxed pre-contracted PAs or PVs to 137% or 127%, respectively. In pre-contracted PAs, the relaxant effect of levosimendan was reduced, if KATP- and Kv-channels were inhibited. Further, levosimendan increased cGMP in PAs/PVs, but cAMP only in PVs. DISCUSSION: Levosimendan reduces rats' segmental PVR and relaxes human PAs or PVs, if the pulmonary vascular tone is enhanced by endothelin-1. Regarding levosimendan-induced relaxation, the activation of KATP- and Kv-channels is of impact, as well as the formation of cAMP and cGMP. In conclusion, our results suggest that levosimendan improves pulmonary haemodynamics, if PVR is increased as it is the case in pulmonary hypertension.

Tyrosine kinase inhibitors relax pulmonary arteries in human and murine precision-cut lung slices.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) inhibit the platelet derived growth factor receptor (PDGFR) and gain increasing significance in the therapy of proliferative diseases, e.g. pulmonary arterial hypertension (PAH). Moreover, TKIs relax pulmonary vessels of rats and guinea pigs. So far, it is unknown, whether TKIs exert relaxation in human and murine pulmonary vessels. Thus, we studied the effects of TKIs and the PDGFR-agonist PDGF-BB in precision-cut lung slices (PCLS) from both species. METHODS: The vascular effects of imatinib (mice/human) or nilotinib (human) were studied in Endothelin-1 (ET-1) pre-constricted pulmonary arteries (PAs) or veins (PVs) by videomicroscopy. Baseline initial vessel area (IVA) was defined as 100%. With regard to TKI-induced relaxation, K+-channel activation was studied in human PAs (PCLS) and imatinib/nilotinib-related changes of cAMP and cGMP were analysed in human PAs/PVs (ELISA). Finally, the contractile potency of PDGF-BB was explored in PCLS (mice/human). RESULTS: Murine PCLS: Imatinib (10 µM) relaxed ET-1-pre-constricted PAs to 167% of IVA. Vice versa, 100 nM PDGF-BB contracted PAs to 60% of IVA and pre-treatment with imatinib or amlodipine prevented PDGF-BB-induced contraction. Murine PVs reacted only slightly to imatinib or PDGF-BB. Human PCLS: 100 µM imatinib or nilotinib relaxed ET-1-pre-constricted PAs to 166% or 145% of IVA, respectively, due to the activation of KATP-, BKCa2+- or Kv-channels. In PVs, imatinib exerted only slight relaxation and nilotinib had no effect. Imatinib and nilotinib increased cAMP in human PAs, but not in PVs. In addition, PDGF-BB contracted human PAs/PVs, which was prevented by imatinib. CONCLUSIONS: TKIs relax pre-constricted PAs/PVs from both, mice and humans. In human PAs, the activation of K+-channels and the generation of cAMP are relevant for TKI-induced relaxation. Vice versa, PDGF-BB contracts PAs/PVs (human/mice) due to PDGFR. In murine PAs, PDGF-BB-induced contraction depends on intracellular calcium. So, PDGFR regulates the tone of PAs/PVs. Since TKIs combine relaxant and antiproliferative effects, they may be promising in therapy of PAH.

Polytetrafluoroethylene-coated pacemaker leads as surgical management of contact allergy to silicone.

We have previously reported an 18-year-old girl with a congenital heart defect who developed complete heart block after one of her corrective surgeries and who needed an epicardial pacemaker implantation. She developed contact sensitivity to silicone compounds. The problem was solved by implanting a silicone-free pacemaker system utilizing silicone-free transvenous leads. The patient was readmitted 2 years later due to lead failure. As no silicone-free epicardial leads were available, we decided to use standard silicone epicardial leads and enclose the whole system in Gore-Tex material (W.L. Gore & Associates, Flagstaff, AZ). Based on our experience we would discourage the use of silicone-free transvenous pacing leads for epicardial use.

EuroScore 2 for identification of patients for transapical aortic valve replacement--a single center retrospective in 206 patients.

BACKGROUND: Operative risk scoring algorithms identify patients with severe AS for transcatheter valve implantation in whom the anticipated operative mortality for conventional surgery would be considered prohibitive. We compared the three risk scores EuroScore 1 (LES), society of thoracic surgeons' (STS) score and ACEF (age-creatinine-ejection fraction score) to the readjusted EuroScore 2 recently presented. METHODS: We reviewed all consecutive patients receiving either isolated conventional aortic valve replacement (cAVR) or transapical aortic valve implantation (TA-TAVI) in a two-year period (n = 206). 30-days mortality was considered as primary endpoint. RESULTS: TA-TAVI was performed in 76 patients, isolated cAVR in 130 patients. Overall mortality was 4.4% (TA-TAVI: 7.9%; cAVR: 2.3%). EuroScore 2 showed a good estimation for the entire population as well as within the subgroups: 4,02 ± 5,36% (TA-TAVI: 6.16 ± 7.14%, cAVR: 2.77 ± 3.42%). Predicted mortalities as assessed by LES were largely overestimated (TA-TAVI: 27.4 ± 20.9% cAVR: 10.6 ± 10.6%, sensitivity: 0.89, specificity: 0.71). STS predicted mortality was 6.3 ± 4.4% for TA-TAVI patients as to 3.2 ± 3.1% for cAVR patients (sens.: 0.22, spec.: 0.96) and ACEF predicted a mortality of 1.16 ± 0.36% for cAVR and 1.58 ± 0.59% for TA-TAVI patients (sens.: 0.78, spec.: 0.89). CONCLUSION: The newly refined EuroScore 2 showed a good correlation within the studied population. For the individual patient, new cut-offs will have to be defined to triage patients for TAVI procedure. A drawback for complex score systems such as EuroScore and STS is the lack of recalibration to smaller populations as encountered in even large single centers.

In vivo remodeling and structural characterization of fibrin-based tissue-engineered heart valves in the adult sheep model.

Autologous fibrin-based tissue-engineered heart valves have demonstrated excellent potential as patient-derived valve replacements. The present pilot study aims to evaluate the structure and mechanical durability of fibrin-based heart valves after implantation in a large-animal model (sheep). Tissue-engineered heart valves were molded using a fibrin scaffold and autologous arterial-derived cells before 28 days of mechanical conditioning. Conditioned valves were subsequently implanted in the pulmonary trunk of the same animals from which the cells were harvested. After 3 months in vivo, explanted valve conduits (n = 4) had remained intact and exhibited native tissue consistency, although leaflets demonstrated insufficiency because of tissue contraction. Routine histology showed remarkable tissue development and cell distribution, along with functional blood vessel ingrowth. A confluent monolayer of endothelial cells was present on the valve surface, as evidenced by scanning electron microscopy and positive von Willebrand factor staining. Immunohistochemistry and extracellular matrix (ECM) assay demonstrated complete resorption of the fibrin scaffold and replacement with ECM proteins. Transmission electron microscopy revealed mature collagen formation and viable, active resident tissue cells. The preliminary findings of implanted fibrin-based tissue-engineered heart valves are encouraging, with excellent tissue remodeling and structural durability after 3 months in vivo. The results from this pilot study highlight the potential for construction of completely "autologous" customized tissue-engineered heart valves based on a patient-derived fibrin scaffold.

Allergy to pacemaker silicone compounds: recognition and surgical management.

Silicone is a widely used biomaterial. Contact allergy, particularly to silicone components of pacemaker coatings, is uncommon. We present a 12-year-old girl with a history of complex congenital heart disease and acquired complete heart block excluding transvenous lead placement. Contact allergy to silicone led to multiple surgical interventions until the etiology for recurrent pacemaker wound complications was discovered. The key to diagnosis was a specific manufacturer's patch test. Complete removal of the former pacing system and placement of custom-made silicone free pacemaker components and epicardial use of silicone free transvenous leads were essential for successful therapy.

Development of a miniaturized heart-lung machine for neonates with congenital heart defect.

Predominantly, standard adult heart lung machines are used for pediatric cardiac surgery, only with individually downsized components. Downsizing is limited, e.g., by the required gas exchange surface. To diminish complications, we developed a new miniaturized heart lung machine (MiniHLM) for neonates, with significantly reduced priming volume and blood contact surface by integration of all major system components in one single device. In particular, a rotary blood pump is centrically integrated into the oxygenator and the cardiotomy reservoir with integrated heat exchanger is directly connected. Thus, tubing is only necessary between patient and MiniHLM. A total priming volume of 102 ml could be achieved for the entire extracorporeal circuit (including arterial/venous line), in contrast to the currently smallest device on the market with 213 ml. In first animal experiments with female New Zealand rabbits, the MiniHLM guaranteed both a sufficient gas exchange and an adequate blood flow; 12 rabbits could successfully be weaned off after 1 hour of aortic clamp time. The first in vitro and in vivo tests confirm the concept of the MiniHLM. Its low priming volume and blood contact surface may significantly reduce complications during heart surgery in neonates.