Thrombolytic treatment of prosthetic valve thrombosis: a study using Urokinase

Objective We analysed the efficacy and safety of thrombolytic therapy with urokinase in patients with prosthetic valve thrombosis. Methods Twenty-three patients with valve thrombosis received thrombolytic treatment using urokinase. First, a 250,000 IU intravenous bolus injection was administered as a loading dose, followed by intravenous infusion of 100,000 IU/h for 10 h and anticoagulation with low molecular weight heparin every day. The maximum treatment time was 5 days, i.e., until the transvalvular pressure gradient was normal or close to normal. Transthoracic echocardiography (TTE) was used every 12 h to monitor whether the thrombus was reduced and whether there was haemodynamic improvement. Routine blood tests, the prothrombin time (PT), international normalized ratio (INR) and complications were observed every day. Results Sixteen (69.6%) patients were successfully treated with thrombolytic therapy: 2/2 (100%) aortic valves and 14/21 (66.7%) mitral valves. The partial success rate of this study was 13.0% (3/23). Four patients did not show any improvement in haemodynamics. Two cases had slight urine haemorrhage. One patient died of severe cerebral haemorrhage and shock. The overall mortality was 13.0% (3/23), including two patients who died after subsequent surgery. Conclusion Urokinase is more convenient and successful in the treatment of PVT. More experience may make TT the optimal treatment for PVT, especially in high-risk surgical situations.

Pulmonary vasculature

A 16-year-old girl with a diagnosis of diffuse cutaneous systemic sclerosis is referred to a specialist pulmonary hypertension centre with a history of progressive breathlessness, reduced exercise tolerance, and raised pulmonary pressures on transthoracic echocardiogram. She is found to have pulmonary arterial hypertension on right cardiac catheterization and is started on sildenafil, a phosphodiesterase-5 inhibitor, which stabilizes her condition. An endothelin receptor antagonist is added, which provides some initial symptomatic improvement. She continues to deteriorate over a period of 5 years, ultimately requiring intravenous prostanoids, the only treatment to provide a real symptomatic and haemodynamic improvement. This chapter explores the physiology and pathophysiology of pulmonary arterial hypertension, its classification, the means of investigation and diagnosis, who to refer to specialist centres, and the concepts behind current and future treatment strategies.

The Role of Percutaneous Haemodynamic Support in High-risk Percutaneous Coronary Intervention and Cardiogenic Shock

The experience and usage of percutaneous cardiac assist devices in cardiogenic shock as well as high-risk percutaneous coronary intervention have increased over the years. Nonetheless, there is still little evidence of clinical benefit of these devices other than immediate haemodynamic improvement. Despite the fact that these devices are used to treat a rather complex patient population, clinical testing remains important in order to evaluate their true impact on clinical outcome before being adopted into clinical practice. Therefore, this review shows an overview of the current experience and evidence of the available percutaneous cardiac assist devices.

Pulmonary Oedema—Therapeutic Targets

Pulmonary oedema (PO) is a common manifestation of acute heart failure (AHF) and is associated with a high-acuity presentation and with poor in-hospital outcomes. The clinical picture of PO is dominated by signs of pulmonary congestion, and its pathogenesis has been attributed predominantly to an imbalance in Starling forces across the alveolar–capillary barrier. However, recent studies have demonstrated that PO formation and resolution is critically regulated by active endothelial and alveolar signalling. PO represents a medical emergency and treatment should be individually tailored to the urgency of the presentation and acute haemodynamic characteristics. Although, the majority of patients admitted with PO rapidly improve as result of conventional intravenous (IV) therapies, treatment of PO remains largely opinion based as there is a general lack of good evidence to guide therapy. Furthermore, none of these therapies showed simultaneous benefit for symptomatic relief, haemodynamic improvement, increased survival and end-organ protection. Future research is required to develop innovative pharmacotherapies capable of relieving congestion while simultaneously preventing end-organ damage.

Pulmonary arterial hypertension in patients treated with interferon

Isolated cases of pulmonary arterial hypertension (PAH) in patients treated with interferon (IFN) α or β have been reported in the literature.The aim of this study was to describe all consecutive cases of PAH patients with a history of IFN exposure identified in the French reference centre for severe pulmonary hypertension between 1998 and 2012.A total of 53 patients with PAH and a history of IFN therapy were identified. 48 patients had been treated with IFNα for chronic hepatitis C. Most of them had portal hypertension (85%) and 56% had HIV co-infection. Five additional patients had been treated with IFNβ for multiple sclerosis. The diagnosis of PAH was made within 3 years after IFN therapy in 66% of patients. Repeated haemodynamic assessment was available in 13 out of 16 patients exposed to IFN after the diagnosis of PAH. Increased pulmonary vascular resistance >20% was observed in 11 out of 13 cases (median 43% increase; IQR 32–67%). In five of these patients, IFN withdrawal resulted in spontaneous haemodynamic improvement.This retrospective analysis suggests that IFN therapy may trigger PAH. However, most of these patients had other risk factors for PAH. A prospective case–control study is necessary to definitively establish a link between IFN exposure and PAH.

Pharmacological modulation of procoagulant microparticles improves haemodynamic dysfunction during septic shock in rats

SummaryCirculating microparticles play a pro-inflammatory and procoagulant detrimental role in the vascular dysfunction of septic shock. It was the objective of this study to investigate mechanisms by which a pharmacological modulation of microparticles could affect vascular dysfunction in a rat model of septic shock. Septic or sham rats were treated by activated protein C (aPC) and resuscitated during 4 hours. Their microparticles were harvested and inoculated to another set of healthy recipient rats. Haemodynamic parameters were monitored, circulating total procoagulant microparticles assessed by prothrombinase assay, and their cell origin characterised. Mesenteric resistance arteries, aorta and heart were harvested for western blotting analysis. We found that a) the amount and phenotype of circulating microparticles were altered in septic rats with an enhanced endothelial, leucocyte and platelet contribution; b) aPC treatment significantly reduced the generation of leucocyte microparticles and norepinephrine requirements to reach the mean arterial pressure target in septic rats; c) Microparticles from untreated septic rats, but not from aPC-treated ones, significantly reduced the healthy recipients’ mean arterial pressure; d) Microparticle thromboxane content and aPC activity were significantly increased in aPC-treated septic rats. In inoculated naïve recipients, microparticles from aPC-treated septic rats prompted reduced NF-κB and cyclooxygenase-2 arterial activation, blunted the generation of pro-inflammatory iNOS and secondarily increased platelet and endothelial microparticles. In conclusion, in this septic shock model, increased circulating levels of procoagulant microparticles led to negative haemodynamic outcomes. Pharmacological treatment by aPC modified the cell origin and levels of circulating microparticles, thereby limiting vascular inflammation and favouring haemodynamic improvement.