Panagiotis Vasileiou

Anakinra for the management of resistant idiopathic recurrent pericarditis. Initial experience in 10 adult cases

Recurrent idiopathic pericarditis is a common, problematic complication of acute pericarditis, occurring in approximately 30% of cases.1 Despite appropriate management with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids (CS), a number of patients are either resistant to treatment requiring long-term therapy with high doses of CS or intolerant to therapy.2–4 This disease is currently viewed as an autoinflammatory disease based on its clinical and laboratory features (recurrent episodes of sterile serosal inflammation in the absence of specific autoreactive antibodies or T cells),5–7 and the preliminary results showing favourable response to intereleukin-1 (IL-1) inhibition.8–10 Anakinra, a known IL-1 receptor antagonist, has been successfully used in small series of paediatric patients8 ,9 while we have recently first reported its efficacy and safety in three adult patients.10 In this report, we extend our follow-up on these three patients, and present data on seven more adult patients treated with anakinra. …

Successful treatment of adult patients with idiopathic recurrent pericarditis with an interleukin-1 receptor antagonist (anakinra)

Idiopathic recurrent pericarditis (IRP) is observed in 10–30% of cases after a first episode of acute pericarditis, whereas a second recurrence appears in anevenhigher rate (~50%) [1,2]. Although severalmechanisms have been suggested to explain recurrence, most of them appear simply contributory. Today, there is increasing evidence that autoimmune and autoinflammatory pathways aremainly involved in its pathogenesis [3,4]. The optimal regimen for treating IRP has not been established [1]. Several medications either alone or in combination have been tested including nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin, colchicine, corticosteroids, and immunosuppressive agents. To date, the only available medication proved in randomized trials to decrease the recurrence rate is colchicine [2]. However, even with colchicine, a substantial proportion of patients experience recurrences [2]. Recently, Picco and et al. reported the successful use of an interleukin1β receptor antagonist anakinra in three children with resistant IRP [4]. Here, we present our experience in three adults with drug resistant or intolerant IRP. All patients were informed in detail regarding the management with anakinra and gave informed consent. Case#1: A 26-year-oldmale had suffered 8 episodes of IRP since 2004. He has received various regimens including NSAIDs, colchicine, steroids and azathioprine (Fig. 2A). In October 2006 treatment with prednisone was instituted but his symptoms recurred every time the dose was tapered below 15mg/day. Unfortunately, the patient developed steroidrelated complications including glaucoma, osteopenia and proximal myopathy of the lower extremities. In his latest admission inMarch 2010, the patient was started on anakinra (150 mg/day subcutaneously, SC) as monotherapy for 3 months and steroidswere tapered off. Administration of anakinrawas followed byan immediate and dramatic clinical response International Journal of Cardiology 160 (2012) 66–77

Anakinra: an emerging option for refractory idiopathic recurrent pericarditis

Aims Accumulating evidence suggests idiopathic recurrent pericarditis as a disease of probable autoinflammatory origin, and thus anakinra could be of benefit. The goal of this systematic review was to assess the efficacy and safety of anakinra in this context. Methods Reports relevant to anakinra administration in patients with idiopathic recurrent pericarditis published up to October 2014 were searched in several databases. All references found, upon initial assessment at title and abstract level for suitability, were consequently retrieved as full reports for further appraisal. Results Among 12 citations retrieved, nine reports (four case series and five case reports with 34 patients, 20 men, mean age 26.8 years) were assessed. The mean disease duration was 31 months and the number of recurrences 8.2. Anakinra was generally administered as a daily subcutaneous injection of 100 mg or as a mean dose of 1.1 mg/kg/d in weight-adjusted regimens. The mean full-dose duration was 9.2 months. C-reactive protein normalized within 7.1 days, and steroids were withdrawn within 62 days. Dose tapering was adopted in 64.7% of patients, leading to recurrence in 26% of cases. In a 28.3-month follow-up, eight out of 34 patients (23.5%) were disease free without treatment, after having received anakinra for 10.4 months overall. Anakinra was proved well tolerated, with mild local reaction being reported in 44% of patients. Conclusion Anakinra is a highly effective, rapidly acting, well tolerated and steroid-sparing agent. Recurrences after drug discontinuation are a matter of concern. Randomized trials are required to confirm these findings and address the most effective treatment protocol.

Incidence and prognostic significance of new onset atrial fibrillation/flutter in acute pericarditis

Objective Data on the incidence of new onset atrial fibrillation and flutter (AF/f) in patients with acute pericarditis are limited. We sought to determine the incidence and prognostic significance of AF/f in this setting. Methods Between January 2006 and June 2014, consecutive new cases of acute pericarditis were included in two urban referral centres for pericardial diseases. All new cases of AF/f defined as episodes lasting ≥30 s were recorded. Events considered during follow-up consisted of AF/f and pericarditis recurrence, cardiac tamponade, pericardial constriction and death. Results 822 consecutive new cases of acute pericarditis (mean age 53±15 years, 444 men) were analysed. AF/f was detected in 35 patients (4.3%, mean age 66.5±11.3 years, 18 men). Patients with AF/f were significantly older (p=0.017) and presented more frequently with pericardial effusion (p<0.001). Arrhythmias developed within 24 h of pericarditis onset in 91.4% of cases, lasted >24 h in 25.7% and spontaneously converted in 74.3% of patients. Underlying structural heart disease was present in 17% of AF/f cases. In a 30-month follow-up, patients with history of AF/f at the initial episode had a higher rate of arrhythmia occurrence (34.3% vs 0.9%, p<0.001), mostly (75%) within 3 months. No other differences were detected in additional clinical events including haemorrhagic complications in patients receiving oral anticoagulation. Conclusions The occurrence of AF/f in acute pericarditis identifies a predisposed population to AF/f with a high recurrence risk (about 35%): in these patients, pericarditis may act as an arrhythmic trigger and oral anticoagulation should be seriously considered according to guidelines.

The Potential Role of Erythropoietin as a Pleiotropic Agent in Post-cardiac Arrest Syndrome

Sudden cardiac arrest is a leading cause of death worldwide with survival rates still remaining suboptimal. Unfortunately, most cardiac arrest patients, who achieve return of spontaneous circulation (ROSC), develop a multi-faceted post-cardiac arrest syndrome, including post-cardiac arrest brain injury, myocardial dysfunction, and systemic ischemia/reperfusion response. Erythropoietin (EPO), the principal hematopoietic hormone regulating erythropoiesis, exhibits diverse cellular effects in nonhematopoietic tissues. Due to its anti-apoptotic, anti-inflammatory, and anti-oxidant properties, as well as its angiogenic action, EPO plays a role in neuroprotection and cardioprotection. In this regard, EPO represents a promising agent in the cardiac arrest setting, based on a therapeutic strategy that focuses on the post-resuscitation phase. This review aims to provide a comprehensive account of EPOs role in the treatment of each individual component of post-cardiac arrest syndrome.

Erythropoetin as a novel agent with pleiotropic effects against acute lung injury

Current pharmacotherapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is not optimal, and the biological and physiological complexity of these severe lung injury syndromes requires consideration of combined-agent treatments or agents with pleiotropic action. In this regard, exogenous erythropoietin (EPO) represents a possible candidate since a number of preclinical studies have revealed beneficial effects of EPO administration in various experimental models of ALI. Taken together, this treatment strategy is not a single mediator approach, but it rather provides protection by modulating multiple levels of early signaling pathways involved in apoptosis, inflammation, and peroxidation, potentially restoring overall homeostasis. Furthermore, EPO appears to confer vascular protection by promoting angiogenesis. However, only preliminary studies exist and more experimental and clinical studies are necessary to clarify the efficacy and potentially cytoprotective mechanisms of EPO action. In addition to the attempts to optimize the dose and timing of EPO administration, it would be of great value to minimize any potential toxicity, which is essential for EPO to fulfill its role as a potential candidate for the treatment of ALI in routine clinical practice. The present article reviews recent advances that have elucidated biological and biochemical activities of EPO that may be potentially applicable for ALI/ARDS management.

Intravenous human immunoglobulins for refractory recurrent pericarditis: a systematic review of all published cases.

Aims Refractory recurrent pericarditis is a major clinical challenge after colchicine failure, especially in corticosteroid-dependent patients. Human intravenous immunoglobulins (IVIGs) have been proposed as possible therapeutic options for these cases. The goal of this systematic review is to assess the efficacy and safety of IVIGs in this context. Methods Studies reporting the use of IVIG for the treatment of recurrent pericarditis and published up to October 2014 were searched in several databases. All references found, upon initial assessment at title and abstract level for suitability, were consequently retrieved as full reports for further appraisal. Results Among the 18 citations retrieved, 17 reports (4 case series and 13 single case reports, with an overall population of 30 patients) were included. The mean disease duration was 14 months and the mean number of recurrences before IVIG was 3. Approximately 47% of patients had idiopathic recurrent pericarditis, 10% had an infective cause, and the remainder a systemic inflammatory disease. Nineteen out of the 30 patients (63.3%) were on corticosteroids at IVIG commencement. IVIGs were generally administered at a dose of 400–500 mg/kg/day for 5 consecutive days with repeated cycles according to the clinical response. Complications were uncommon (headache in ∼3%) and not life-threatening. After a mean follow-up of approximately 33th months, recurrences occurred in 26.6% of cases after the first IVIG cycle, and 22 of the 30 patients (73.3%) were recurrence-free. Five patients (16.6%) were on corticosteroids at the end of the follow-up. Conclusions IVIGs are rapidly acting, well tolerated, and efficacious steroid-sparing agents in refractory pericarditis.

Erythropoietin administration facilitates return of spontaneous circulation and improves survival in a pig model of cardiac arrest.

BACKGROUND In addition to its role in the endogenous control of erythropoiesis, recombinant human erythropoietin (rh-EPO) has been shown to exert tissue protective properties in various experimental models. However, its role in the cardiac arrest (CA) setting has not yet been adequately investigated. AIM The aim of this study is to examine the effect of rh-EPO in a pig model of ventricular fibrillation (VF)-induced CA. METHODS Ventricular fibrillation was electrically induced in 20 piglets and maintained untreated for 8 minutes before attempting resuscitation. Animals were randomized to receive rh-EPO (5000 IU/kg, erythropoietin [EPO] group, n = 10) immediately before the initiation of chest compressions or to receive 0.9% Sodium chloride solution instead (control group, n = 10). RESULTS Compared with the control, the EPO group had higher rates of return of spontaneous circulation (ROSC) (100% vs 60%, P = .011) and higher 48-hour survival (100% vs 40%, P = .001). Diastolic aortic pressure and coronary perfusion pressure during cardiopulmonary resuscitation were significantly higher in the EPO group compared with the control group. Erythropoietin-treated animals required fewer number of shocks in comparison with animals that received normal saline (P = .04). Furthermore, the neurologic alertness score was higher in the EPO group compared with that of the control group at 24 (P = .004) and 48 hours (P = .021). CONCLUSION Administration of rh-EPO in a pig model of VF-induced CA just before reperfusion facilitates ROSC and improves survival rates as well as hemodynamic variables.

Inexperienced nurses and doctors are equally efficient in managing the airway in a manikin model

OBJECTIVE The aim of the present study was to investigate whether minimally trained medical and nursing school graduates would be equally efficient in placing a laryngeal mask airway (LMA) and in intubating the trachea with the Macintosh blade or a videolaryngoscope in a manikin model. Airway management is an essential skill for both physicians and nurses who may be confronted with a critically ill patient, because in the emergency department the airway is not exclusively managed by medical personnel. Several studies have shown that other healthcare professionals are not any less efficient in securing the airway. METHODS Ninety-six graduates from medical and nursing faculties comprised our study population. After a brief educational session, participants were randomly allocated into 3 groups to secure the airway in manikins with 3 techniques: LMA (The Laryngeal Mask Company Limited, Buckinghamshire, UK) insertion and intubation with the Macintosh blade and with a videolaryngoscope (GlideScope, Verathon Inc, Bothell, WA). The number of attempts until the first successful intubation, time required for the first successful attempt, and severity of dental trauma were assessed. RESULTS No statistically significant difference was observed between physicians and nurses in the number of attempts and in the time required for the first successful attempt with any of the 3 techniques studied. From the 3 techniques studied, LMA placement was the fastest (P < .001). No significant difference was observed between physicians and nurses in the severity of dental trauma. CONCLUSION Nurses are as efficient as physicians in managing the airway safely and adequately with the 3 different techniques in manikins.

Prognostic implications of epicardial fat volume quantification in acute pericarditis

The pathophysiology of acute pericarditis remains largely unknown, and biomarkers are needed to identify patients susceptible to complications. As adipose tissue has a pivotal role in cardiovascular disease pathogenesis, we hypothesized that quantification of epicardial fat volume (EFV) provides prognostic information in patients with acute pericarditis.