[Pulmonary hypertension associated with left heart disease: recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Linksherzerkrankungen: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more common forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern because of limited ressources and the need to base treatments on scientific evidence. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, representing an unmet need of targeted PH therapies. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, several working groups were initiated, one of which was specifically dedicated to PH associated with left heart disease. This article summarizes the results and recommendations of this working group.

[Pulmonary hypertension: hemodynamic evaluation: hemodynamic evaluation ­ recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie: invasive Diagnostik: Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) have been adopted for Germany. Invasive hemodynamic data obtained by right heart catheterization are essential to confirm the diagnosis, test vasoreactivity, assess severity and guide therapy in PH patients. The definition of PH is resting on a mean pulmonary artery pressure ≥ 25 mm Hg obtained by right heart catheterization. Furthermore, a pulmonary capillary wedge pressure > 15 mm Hg excludes pre-capillary PH. Vasoreactivity testing is part of the diagnostic work-up in pulmonary arterial hypertension. Recent data on the use of inhaled iloprost update these guidelines and are of special importance due to the frequent diagnostic use of iloprost in Germany. Other aspects of invasive hemodynamic data in certain PH subgroups as well as their measurement and interpretation in children are discussed. Several aspects of right heart catheterization in PH justify a detailed commentary, and in some areas an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Paediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups were initiated, one of which was specifically addressing the invasive hemodynamic evaluation of patients with PH. This commentary summarizes the results and recommendations of this working group.

A rare but life-threatening complication of ventriculo-atrial shunt.

Insertion of ventriculoperitoneal and ventriculoatrial shunts is routinely performed. Infarction pneumonia and atrial thrombus formation are described as very rare complications of ventriculoatrial shunts. We present the case of a female patient with ventriculoatrial shunt insertion as long term treatment for aequeductal stenosis who presented with recurrent episodes of dyspnoea, chest pain, and unilateral pleural effusion. Diagnostic evaluation revealed a positive D-dimer test, bilateral basal infiltrates and pleural effusion. Transesophageal echocardiography established the diagnosis of a thrombus in the right atrium. Laboratory testing for thrombophilia revealed a homozygous factor V Leiden mutation. In the following, a shunt revision was performed.

Superiority of sirolimus eluting stent compared with intracoronary beta radiation for treatment of in-stent restenosis: a matched comparison.

OBJECTIVE: To compare acute and follow up clinical and angiographic results after treatment of in-stent restenosis (ISR) by sirolimus eluting stents (SES) with results obtained after intracoronary radiation therapy (IRT). DESIGN: Matched pair analysis. METHODS: 62 consecutive ISR lesions (< 30 mm lesion length, reference diameter < 3.5 mm) in 62 patients were treated with SES. From a database of 174 lesions (n = 141 patients) treated for ISR by intracoronary beta radiation, 62 lesions (62 patients) were pair matched with the SES group for diabetes mellitus, lesion length, vessel size, and pattern of ISR. Six month angiographic and 12 month clinical follow up results were obtained. RESULTS: Baseline clinical and angiographic characteristics were similar between the groups (not significant). SES implantation resulted in significantly lower postprocedural in-lesion diameter stenosis than did IRT (mean (SD) 14.2 (9.5)% v 21.1 (10.6)%, p = 0.001), significantly higher minimum lumen diameter at follow up (1.91 (0.58) v 1.55 (0.72) mm, p = 0.005), and a higher net gain (1.16 (0.55) v 0.77 (0.70) mm, p = 0.002). Angiographic binary in-lesion restenosis rate at six months was 11% in the SES group and 29% in the IRT group (p = 0.046). In 16 ISR lesions SES were used after failed IRT and in 46 lesions for first time ISR. In-lesion late loss was higher after use of SES for failed IRT than after use of SES for first time ISR (0.61 (0.67) mm v 0.24 (0.41) mm, p = 0.018). In a multivariate analysis prior failed IRT was the only independent predictor for recurrent restenosis after SES for ISR (p = 0.052, odds ratio 5.8). Six patients (10%) in the SES group and 17 patients (27%) in the IRT group underwent target lesion revascularisation during the 12 months of follow up (p = 0.022). CONCLUSIONS: In this non-randomised matched cohort SES achieved acute and follow up results superior to IRT for treatment of ISR even if cases of failed IRT are included. Failed IRT is a predictor of impaired SES effectiveness.

A study on the primary and secondary nucleation of ice by power ultrasound.

Several different investigations have been carried out to study the primary and secondary nucleation of ice by sonocrystallisation. Firstly, the primary nucleation of discrete ice crystals in a supercooled sucrose solution has been observed. For increasing concentrations of sucrose solutions from 0 to 45 wt%, the nucleation temperature consistently occurs at a higher nucleation temperature in the presence of ultrasound. The nucleation temperature also increases as the power output and duty cycle of a commercial ultrasonic horn are increased. Snap shot images of the bubble clouds obtained from the ultrasonic horn also show that the number of bubbles appears to increase as the ultrasonic output is increased. This suggests that the nucleation of ice is related to the power output and number of cavitation bubbles. The effect of a single bubble on the sonocrystallisation of ice is discussed. High-speed movies (1120 fps) have shown that the crystallisation appears to occur in the immediate vicinity of the single bubble. In most cases, many crystals are observed and it is not known whether a single ice crystal is being fragmented by the bubble or whether many crystals are being initiated. The bubble appears to undergo a dancing regime, frequently splitting and rejoining and also emitting some small microbubbles. A study on the secondary nucleation of ice in sucrose solutions has been carried out using a unique ultrasonic cold stage device. Images taken using a microscope system show that the pre-existing ice dendrite crystals can be broken up into smaller fragments by an ultrasonic field. Cavitation bubbles appear to be important during the fragmentation process, possibly melting any ice crystals in their path. Flow patterns around cavitation bubbles have also been observed, and these may be responsible for the fragmentation of ice crystals.

A high power ultrasonic array based test cell.

This paper describes the use of finite element (FE) analysis as a tool in the design process for laboratory based ultrasonic test cells. The system was designed to incorporate an array of ultrasonic transducers to provide a pressure focus in the centre of the cell and importantly, operate both above and below the cavitation threshold of the load medium. Furthermore, the cell incorporates a coolant jacket to accommodate temperature control of the load material associated with the process. A 2D FE model corresponding to a slice through the operational plane of the cell was developed and used to investigate the influence of cell wall material and thickness, transducer configuration, rotation of a metallic stirrer blade and heat transfer fluid on the cell acoustic response. Importantly, experimentally measured pressure field maps demonstrate good correlation with the FE predicted fields. A final manufactured test cell is shown to produce a highly focussed region of cavitation. Finally, the importance in accurately representing the acoustic properties of the constituent materials used in such FE models is demonstrated through an illustrated example.

Rotational atherectomy for the treatment of in-stent restenosis.

Restenosis after coronary stent implantation remains the major limitation of this treatment modality. At present, re-dilatation is considered the therapeutic option of choice for focal lesions, however, long restenotic lesions (>10 mm) do not respond favourably. Despite the emerging concept of intracoronary radiation, encouraging acute procedural results are also reported for different debulking techniques (Excimer laser angioplasty, directional coronary atherectomy, and rotational atherectomy, or rotablation). Rotablation has been studied most extensively with acute and long- term results published in a total of more than 850 patients. Experimental and first clinical data indicate favourable results for the rotablator as compared to balloon angioplasty alone for the treatment of in-stent restenosis. Data from the first 2 randomized clinical trials (ROSTER-, and ARTIST-trial) have now been published with conflicting results: The european multicenter ARTIST-trial including 300 patients could not prove a benefit for the rotablator as compared to re-dilatation in patients with diffuse stent restenosis. On the contrary, the monocenter ROSTER-trial, which has been presented as an abstract until today, suggests a clinical benefit of patients treated by the rotablator if they were studied with intracoronary ultrasound prior to randomization. Currently, rotablation for the treatment of restenosis cannot be considered as the first line treatment modality in patients with in-stent restenosis. As a result of unsatisfying angiographic and clinical long-term results by the use of a variety of treatment modalities in diffuse stent restenosis, prevention of this iatrogenic entity has become mandatory.

Abciximab inhibits the migration and invasion potential of human coronary artery smooth muscle cells.

In the EPIC trial, high-risk patients received the integrin receptor antagonist abciximab v placebo during and for 12 h following percutaneous coronary intervention with a significant 23% decrease of repeat revascularisation at 6 months. However, EPILOG and CAPTURE trials could not confirm these promising long-term results. Recently presented data from the EPISTENT trial suggested a beneficial effect of abciximab on restenosis in patients with diabetes. Based on these divergent results the aim of this study was to test whether alpha v beta 3 receptor blockade by abciximab could cause inhibition of human coronary smooth muscle cell (hcSMC) proliferation, migration, and invasion which represent crucial steps during restenosis development. In contrast to quiescent hcSMCs, proliferating cells were capable to migrate towards chemoattractive stimuli and even capable to invade through a basement membrane equivalent. Abciximab and LM609, an alpha v beta 3 specific inhibiting antibody, caused only a modest dose-dependent inhibition of hcSMC proliferation. On the contrary, the chemotactic and invasive potential of hcSMCs was significantly inhibited by abciximab administration 24 h prior to and during migration. (IC(50)=33.0 microg/ml for chemotaxis and IC(50)=0.5 microg/ml for invasion). For LM609 similar results were obtained. Administration of the drugs just during migration without pretreatment inhibited migration equally but invasion to a lower extent (abciximab: IC(50)=32.6 microg/ml for chemotaxis and IC(50)=44.9 microg/ml for invasion; LM609 IC(50)=3.1 microg/ml for chemotaxis and IC(50)=2.0 microg/ml for invasion). The attachment to the extracellular matrix proteins collagen I, collagen IV, laminin and vitronectin was not influenced. Pretreatment for 24 h with abciximab or LM609 did not cause a downregulation of the alpha v beta 3-integrin receptor. The results of this study indicate that the alpha v beta 3 antagonist abciximab is a potent inhibitor of hcSMC migration and invasion which could explain the observed lower reintervention rate after PTCA and stent implantation.

Development of a new biodegradable intravascular polymer stent with simultaneous incorporation of bioactive substances.

OBJECTIVE: Due to the thrombogenicity and permanent implant nature of metallic stents, bioresorable synthetic polymers have been proposed for stents and local drug delivery systems. Bioresorbable polyesters like poly(D,L-lactide) demonstrated excellent biocompatibility in various tissues. This paper describes a novel method for the molding of these polymers. The specific CESP-process (Controlled Expansion of Saturated Polymers) is characterised by the use of the plasticizer carbon dioxide and allows the incorporation of bioactive substances at physiologic temperatures into the polymer bulk and the production of complex designed implants. METHODS: The CESP-process is characterised by the exposure of an amorphous polymer to an inert gas at high pressure with a significant lower glass transition point. The plasticizing effect makes it possible to process polylactides at a temperature close to room temperature. The low process temperature constitutes a key advantage for thermally sensitive polymers and allows the incorporation of thermally sensitive pharmaceutical additives. To obtain some preliminary information on the biocompatibility, in vitro cell toxicity testing as well as drug release assessment was performed. RESULTS: Different polymer sheets were produced using the CESP-process. Cytotoxicity was not observed in any molded polymer material. According to the mechanical and biocompatibility results Poly(D,L-lactide) (P-DL-LA) was investigated in the CESP-process. Finite element analysis was used to test the possible geometry of an adequate stent. A helical design was chosen and a stent-prototype was produced using the CESP-process. Peroxidase activity as an incorporated marker enzyme could be measured over 6 weeks. Different drug release profiles were obtained due to various pore sizes of the polymer. CONCLUSIONS: The new CESP-process can be used to process biodegradable polymers and to mold different stent geometries without inducing cytotoxic effects to the material. Furthermore, this procedure permits the simultaneous incorporation of bioactive substances during the molding process. Drug release kinetics can be regulated by different pore sizes of the material.