Liver function abnormalities, clinical profile, and outcome in acute decompensated heart failure.

AIMS: The aim of this study was to assess the prevalence of abnormal liver function tests (LFTs) and the associated clinical profile and outcome(s) in acute decompensated heart failure (ADHF) patients. Alteration in LFTs is a recognized feature of ADHF, but prevalence and outcomes data from a broad contemporary cohort of ADHF are scarce and the mechanism(s) of ADHF-induced cholestasis is unknown. METHODS AND RESULTS: We conducted a post hoc analysis of SURVIVE, a large clinical trial including ADHF patients treated with levosimendan or dobutamine. All LFTs were available in 1134 patients at baseline. Abnormal LFTs were seen in 46% of ADHF patients: isolated abnormal alkaline phosphatase (AP) was noted in 11%, isolated abnormal transaminases in 26%, and a combination of abnormal AP and transaminases in 9%. Abnormal AP was associated with marked signs of systemic congestion and elevated right-sided filling pressure. Abnormal AP had no relationship with 31-day mortality but was associated with worse 180-day mortality (23.5 vs. 34.9%, P = 0.001 vs. patients with normal AP). Abnormal transaminases were associated with clinical signs of hypoperfusion and with greater 31-day and 180-day mortality compared with normal transaminase profiles (17.6 vs. 8.4% and 31.6 vs. 22.4%, respectively; both P < 0.001). There was no additive value of abnormal AP plus abnormal transaminase on a long-term outcome. CONCLUSION: Abnormal LFTs were present in about a half of patients presenting with ADHF treated with inotropes. Abnormal AP and abnormal transaminases were associated with specific clinical, biological, and prognostic features, including a short-term overmortality with increased transaminases but not with biological signs of cholestasis, in ADHF patients.

Atrial fibrillation post CABG and the risk of arrhythmia recurrence: the AFRODITE study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) after coronary artery bypass surgery (CABG) occurs with an incidence of 20-40%. The clinical relevance of POAF remains a concern, and the need for further studies regarding the clinical management of POAF is necessary. AIM: The AFRODITE study, a prospective multicenter cohort study, had as its primary endpoint the evaluation of AF recurrence in patients post CABG over a one-year period. METHODS: Two hundred twenty-eight patients aged >50 years who underwent isolated CABG were included in the study. Patients were stratified into two groups, POAF and non-POAF, and followed for 12 months for AF recurrence, hospitalizations, and death. RESULTS: Two hundred twenty-eight patients (mean age 67 years, 88.6% male) were included in the study. 28.5% of patients experienced at least one episode of POAF during index hospitalization (POAF group) and were compared with the non-POAF group (n = 163). Multivariate stepwise logistic regression analysis showed that the strongest prognostic parameter for POAF was the CHA2DS2-VASc score (odds ratio = 1.61, p < 0.001). POAF patients had a worse in-hospital outcome, but the incidence of long-term AF recurrence was not statistically different (3.6% vs. 4.8%, p = 0.9). CONCLUSION: Interestingly, a one-year prospective follow-up of patients in the study did not reveal significant differences between POAF and non-POAF patients. A notable finding was that patients with a higher CHA2DS2-VASc score were more likely to develop POAF.

Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute CardioVascular Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of Cardiology.

Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence-based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear-cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF.

Effects of sertraline on circulating markers of oxidative stress in depressed patients with chronic heart failure: a pilot study.

BACKGROUND: Depression is a common comorbid condition in patients with chronic heart failure (CHF). This pilot study investigated the plasma levels of oxidative stress markers in depressed CHF patients as well as the effects of antidepressant treatment with sertraline on these markers in the same patient population. METHODS AND RESULTS: Patients with positive depression screening [Beck Depression Inventory (BDI) score >10 and/or Zung Self-Rating Depression Scale >40] underwent a psychiatric interview. Patients newly diagnosed as depressed received pharmacologic treatment with sertraline for 3 months (arm A) and were compared with those who did not comply with the antidepressant treatment (arm B). Markers of oxidative stress [malondialdehyde (MDA) and protein carbonyls (PC)], and nitrosative stress [nitrotyrosine (NT)] were assessed at baseline and 3 months later. Fifty-two out of 254 screened hospitalized CHF patients were diagnosed as depressed. Depressed patients had significantly higher levels of MDA compared with age- and gender-matched nondepressed patients (n = 40; 3.2 ± 2.0 vs 2.8 ± 3.8 µmol/L; P = .02). Twenty-eight patients received sertraline (arm A), and 24 refused to receive antidepressant treatment on the top of optimal heart failure treatment (arm B). Although baseline levels of MDA and PC in arm A and arm B did not differ significantly (P > .05), arm A patients demonstrated a significant reduction in MDA (F = 4.657; P = .037) and arm B patients demonstrated no change after 3 months. Regarding the examined scores, arm A patients had a decrease in BDI score (28 ± 11 vs 21 ± 13; P = .008), and arm B patients had no change in BDI score at follow-up (P > .05). Arm A had an increase in 6-minute walking distance (291 ± 110 vs 361 ± 87 m; P = .02), and arm B experienced no change (P > .05). CONCLUSIONS: Increased oxidative stress may play a critical role in the pathophysiology of depression in CHF. Treatment with sertraline improves depressive symptoms and reduces plasma markers of oxidative stress in depressed CHF patients.

Assessment of a commercial EPID dosimetry system to detect radiotherapy treatment errors.

One method for detecting radiotherapy treatment errors is to capture the exit dose using an electronic portal imaging device. In comparison with a baseline integrated image, subsequent fractions can be compared and differences in images suggest a difference in the radiation treatment delivered. The aim of this work was to assess the sensitivity of a commercial software PerFRACTION in detecting such differences, arising from three possible sources: (i) changes in the radiation beam or EPID position; (ii) changes in the patient position; and (iii) changes in the patient anatomy. By systematically introducing errors, PerFRACTION was shown to be very sensitive to changes in the radiation beam. Variation in the beam output could be detected within 0.3%, field size within 0.4 mm, collimator rotation within 0.3° and MLC positioning could be verified to within 0.1 mm. EPID misalignment could be detected within 0.3 mm. PerFRACTION was able to detect the mispositioning of an anthropomorphic phantom by 3 mm with static beams, however there was a relative dependency between the patient geometry and the direction of the shift. VMAT beams were less sensitive to patient misalignments, with a shift of 10 mm only detectable once a strict criterion of 1% dose difference was applied. In another simulated scenario PerFRACTION was also able to detect a weight loss equivalent to a 5 mm change in patient separation in VMAT plans and 10 mm in conformal plans. This work showed that the PerFRACTION software could be relied upon to detect potential radiotherapy treatment errors, arising from a variety of sources.

Effects of Anti-Inflammatory Treatment and Surgical Intervention on Endothelial Glycocalyx, Peripheral and Coronary Microcirculatory Function and Myocardial Deformation in Inflammatory Bowel Disease Patients: A Two-Arms Two-Stage Clinical Trial.

Sixty inflammatory bowel disease (IBD) patients (45 Crohn disease and 15 ulcerative colitis, 40 ± 13 years, 53% male) were examined at baseline and 4 months after intervention (surgical (35 patients) or anti-TNFa treatment (25 patients)). IBD severity, using Mayo score, Harvey-Bradshaw Index (HBI) and biomarkers, was correlated with cardiovascular markers. At baseline, the disease severity, the white blood cells (WBC) values and the reducing power (RP) were significantly correlated with the aortic pulse wave velocity (PWV) (r = 0.4, r = 0.44 and r = 0.48, p < 0.05) and the lateral mitral E' velocity (r = 0.35, p < 0.05 and r = 0.3, p < 0.05). Four months after intervention, there was a reduction of WBC (1962.8/mm3 ± 0.425/mm3, p < 0.001), C-reactive protein (CRP) (8.1 mg/L ± 1.7 mg/L, p < 0.001), malondialdehyde (MDA) (0.81 nmol/mg ± 0.37, p < 0.05) and glycocalyx perfused boundary region (PBR 5-25) (0.24 µm ± 0.05 µm, p < 0.01). Moreover, the brachial flow mediated dilatation (FMD), the coronary flow reserve (CFR) and the left ventricle global longitudinal strain (LV GLS) were significantly improved for both groups (4.5% ± 0.9%, 0.55 ± 0.08, 1.4% ± 0.35%, p < 0.01), while a more significant improvement of PWV/GLS was noticed in the anti-TNFa group. IBD severity is associated with vascular endothelial, cardiac diastolic, and coronary microcirculatory dysfunction. The systemic inflammatory inhibition and the local surgical intervention lead to significant improvement in endothelial function, coronary microcirculation and myocardial deformation.

Superparamagnetic electrospun microrods for magnetically-guided pulmonary drug delivery with magnetic heating.

Controlled pulmonary drug delivery systems employing non-spherical particles as drug carriers attract considerable attention nowadays. Such anisotropic morphologies may travel deeper into the lung airways, thus enabling the efficient accumulation of therapeutic compounds at the point of interest and subsequently their sustained release. This study focuses on the fabrication of electrospun superparamagnetic polymer-based biodegradable microrods consisting of poly(l-lactide) (PLLA), polyethylene oxide (PEO) and oleic acid-coated magnetite nanoparticles (OA·Fe3O4). The production of magnetite-free (0% wt. OA·Fe3O4) and magnetite-loaded (50% and 70% wt. Fe3O4) microrods was realized upon subjecting the as-prepared electrospun fibers to UV irradiation, followed by sonication. Moreover, drug-loaded microrods were fabricated incorporating methyl 4-hydroxybenzoate (MHB) as a model pharmaceutical compound and the drug release profile from both, the drug-loaded membranes and the corresponding microrods was investigated in aqueous media. In addition, the magnetic properties of the produced materials were exploited for remote induction of hyperthermia under AC magnetic field, while the possibility to reduce transport losses and enhance the targeted delivery to lower airways by manipulation of the airborne microrods by DC magnetic field was also demonstrated.

Endothelial and Cardiac Dysfunction in Inflammatory Bowel Diseases: Does Treatment Modify the Inflammatory Load on Arterial and Cardiac Structure and Function?

Inflammatory bowel diseases (IBD), largely represented by Crohn's disease (CD) and ulcerative colitis (UC), alter gastrointestinal physiology and mucosal immunity through a complex inflammatory process. These diseases can lead to significant arterial endothelial dysfunction. There is also evidence linking IBD with a modification of cardiac structure and function. A growing body of research has associated IBD with an acceleration of arterial stiffness and atherosclerosis and an increased risk of cardiovascular (CV) morbidity and mortality. The focus of this review is two-fold. Firstly, the literature on IBD in relation to CV dysfunction was evaluated (mainly based on 25 relevant surveys carried out between 2005 and 2018). The vast majority of these studies support a significant association of IBD with a deterioration in CV function. Secondly, the literature available regarding the effect of IBD treatment on CV dysfunction was considered based on studies published between 2007 and 2018. This literature search suggests that IBD treatment may have the potential to ameliorate CV dysfunction resulting in CV benefits. This review will analyse the literature as well as consider emerging research perspectives regarding how IBD treatment could improve CV dysfunction.

Cardiovascular disease in women: Executive summary of the expert panel statement of women in cardiology of the hellenic cardiological society.

The perception that women represent a low-risk population for cardiovascular (CV) disease (CVD) needs to be reconsidered. Starting from risk factors, women are more likely to be susceptible to unhealthy behaviors and risk factors that have different impact on CV morbidity and mortality as compared to men. Despite the large body of evidence as regards the effect of lifestyle factors on the CVD onset, the gender-specific effect of traditional and non-traditional risk factors on the prognosis of patients with already established CVD has not been well investigated and understood. Furthermore, CVD in women is often misdiagnosed, underestimated, and undertreated. Women also experience hormonal changes from adolescence till elder life that affect CV physiology. Unfortunately, in most of the clinical trials women are underrepresented, leading to the limited knowledge of CV and systemic impact effects of several treatment modalities on women's health. Thus, in this consensus, a group of female cardiologists from the Hellenic Society of Cardiology presents the special features of CVD in women: the different needs in primary and secondary prevention, as well as therapeutic strategies that may be implemented in daily clinical practice to eliminate underestimation and undertreatment of CVD in the female population.

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES-HF Registry.

AIMS: Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. METHODS AND RESULTS: We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter-quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50-60%) on admission vs. 60% (IQR: 55-60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta-blockers (71.9%) and angiotensin-converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. CONCLUSIONS: This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow-up data.

Epidemiology, pathophysiology and contemporary management of cardiogenic shock - a position statement from the Heart Failure Association of the European Society of Cardiology.

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management.

Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis.

BACKGROUND: Interleukin-1 increases nitrooxidative stress. We investigated the effects of a human recombinant interleukin-1a receptor antagonist (anakinra) on nitrooxidative stress and vascular and left ventricular function. METHODS AND RESULTS: In an acute, double-blind trial, 23 patients with rheumatoid arthritis were randomized to receive a single injection of anakinra (150 mg s.c.) or placebo and, after 48 hours, the alternative treatment. At baseline and 3 hours after the injection, we assessed (1) coronary flow reserve, aortic distensibility, systolic and diastolic (Em) velocity of the mitral annulus, and E to Em ratio (E/Em) using echocardiography; (2) flow-mediated, endothelium-dependent dilation of the brachial artery; and (3) malondialdehyde, nitrotyrosine, interleukin-6, endothelin-1, and C-reactive protein. In a chronic, nonrandomized trial, 23 patients received anakinra and 19 received prednisolone for 30 days, after which all indices were reassessed. Compared with baseline, there was a greater reduction in malondialdehyde, nitrotyrosine, interleukin-6, and endothelin-1 and a greater increase in flow-mediated dilation, coronary flow reserve, aortic distensibility, systolic velocity of mitral annulus, and E/Em after anakinra than after placebo (malondialdehyde -25% versus 9%; nitrotyrosine -38% versus -11%; interleukin-6 -29% versus 0.9%; endothelin-1 -36% versus -11%; flow-mediated dilation 45% versus -9%; coronary flow reserve 29% versus 4%; and aortic distensibility 45% versus 2%; P<0.05 for all comparisons). After 30 days of treatment, the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group (P<0.05). CONCLUSIONS: Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin.

Self-assessment of health status is associated with inflammatory activation and predicts long-term outcomes in chronic heart failure.

AIMS: Clinicians lack a generally accepted means for health status assessment in chronic heart failure (CHF). We investigated the correlation between health status and inflammation burden as well as its long-term prognostic value in CHF outpatients. METHODS AND RESULTS: Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed by 137 CHF outpatients (aged 64+/-12 years, mean ejection fraction 27+/-7%). Inflammatory markers [interleukin (IL)-6, IL-10, TNF-alpha, soluble Fas, Fas ligand, ICAM-1, VCAM-1], plasma B-type natriuretic peptide (BNP), 6 min walk test (6MWT), Zung self-rating depression scale, and Beck Depression Inventory were also assessed. Patients were followed for major cardiovascular events (death or hospitalization for disease progression) for up to 250 days. Patients with worse KCCQ-summary (KCCQ-s<50) score had lower 6MWT (P<0.05), and higher BNP (P<0.05) and pro-inflammatory markers (P<0.05) than those with KCCQ-s>or=50. Worse health status was also associated with shorter event-free survival (115+/-12 days for KCCQ-s<50 vs. 214+/-15 days for KCCQ-s>or=50, P=0.0179). Separating patients according KCCQ-functional score (KCCQ-f, cut-off 50) showed similar results. In multivariate Cox regression analysis, only LVEF (HR=0.637, 95% CI 0.450-0.900, P=0.011) and KCCQ-f (HR=0.035, 95% CI 0.002-0.824, P=0.037) were independent predictors of event-free survival at 250 days. CONCLUSION: KCCQ-s reflects neurohormonal and inflammatory burden in CHF. Among studied questionnaires, only KCCQ-f is an independent predictor of long-term event-free survival in CHF.

Management of iron deficiency in chronic heart failure: Practical considerations for clinical use and future directions.

Heart Failure (HF) is a global pandemic with rapidly increasing prevalence. In an attempt to maintain patients well being, the therapeutic interest has expanded to the vicious cycles that confer to HF mortality and morbidity and a number of comorbidities have been targeted. Iron deficiency represents a common comorbid condition that affects outcomes in HF. The treatment of iron deficiency is strongly supported by the cardiologic societies all over the world. Intravenous iron, primarily ferric carboxymaltose, has shown clinical benefit in this setting, irrespective of the anemia status. Practical recommendations though are lacking. In this document, we have tried to cover the practical gap and provide useful details for intravenous iron use.

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus.

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.

Effects of functional electrical stimulation on quality of life and emotional stress in patients with chronic heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy: a randomised, placebo-controlled trial.

OBJECTIVE: Functional electrical stimulation (FES) improves exercise capacity and endothelial function in chronic heart failure (CHF) patients. This study evaluates the impact of FES on quality of life and emotional stress in patients with moderate to severe CHF. METHODS: Thirty patients with stable CHF (24 men; NYHA class II-III; left ventricular ejection fraction <35%) were randomly assigned (2:1) to a 6-week FES training program (n=20) or placebo (n=10). Questionnaires addressing quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ), functional and overall], and emotional stress [Zung self-rating depression scale (SDS), Beck Depression Inventory (BDI)], as well as plasma B-type natriuretic peptide (BNP) and 6-min walking distance test (6MWT) were assessed at baseline and after completion of training protocol. RESULTS: A significant improvement in KCCQ functional (F=76.666, p<0.001), KCCQ overall (F =41.508, p<0.001), BDI (F =17.768, p<0.001) and Zung SDS (F =27.098, p<0.001) was observed in the FES group compared to placebo. Patients in the FES group had also a significant increase in 6MWT (F =19.413, p<0.001) and a trend towards reduction in plasma BNP (F =4.252, p=0.053) compared to placebo. CONCLUSION: FES seems to have a beneficial effect on quality of life, exercise capacity and emotional stress in patients with moderate to severe CHF.

A case of pulmonary vein obstruction: evaluation using newer echocardiographic imaging techniques.

A 59-year-old woman was admitted in our hospital due to persistent cough and dyspnea. Transthoracic 2-dimensional echocardiography demonstrated a cardiac mass (29 x 34 mm) that extended from the right upper pulmonary vein into the left atrium causing the partial obstruction of the right lower vein as indicated by the increased Doppler velocities. Contrast echocardiography confirmed the presence of microcirculation within the mass. During transesophageal (TEE) echocardiographic study, color Doppler imaging and power Doppler imaging (Angio((R)) Vivid 7, GE Medical System, Horten, Norway) demonstrated the presence of vascular flow within the mass. A chest magnetic resonance tomography showed a pulmonary mass of 30 x 25 x 28 mm infiltrating the pulmonary veins. After surgery, biopsy confirmed a high grade mucoepidermoid lung cancer with few large arterioles. The new echocardiographic techniques can reliably differentiate a cardiac tumor from a cardiac thrombus.

Electrohydrodynamic methods for the development of pulmonary drug delivery systems.

Electrospinning and electrospraying are two highly versatile and scalable electrohydrodynamic methods, which have attracted considerable attention during the last years towards the fabrication of polymer-based drug delivery systems. The latter may be obtained in the form of nano- or microfibers (via electrospinning) or as drug-loaded nano- and microparticles (via electrospraying). This review article begins with an introduction on the basic principles and the important influencing parameters governing the electrospinning/electrospraying processes, followed by an overview on their use for the development of nano/microfibers and nano/microparticles destined for use in pharmaceutical applications. Focus is given on research efforts targeting in the formulation of drug delivery systems and devices designed for pulmonary drug delivery applications thus emphasizing on the potential use of electrospinning and electrospraying in the area of inhaled medicines.

Effects of levosimendan on right ventricular function in patients with advanced heart failure.

Right ventricular (RV) dysfunction frequently complicates advanced left ventricular heart failure and contributes to an unfavorable prognosis. Levosimendan is a novel inodilator that beneficially affects hemodynamics and left ventricular systolic and diastolic function in patients with advanced heart failure. However, its effects on RV function have not yet been properly assessed in these patients. In this randomized trial, the impact of levosimendan or placebo on various echocardiographic parameters of RV systolic and diastolic function was investigated in 54 patients with advanced heart failure due to left ventricular systolic dysfunction. Tissue Doppler imaging maximal systolic tricuspid annular velocity (S wave) increased significantly only in the levosimendan group (8.2 +/- 3.2 vs 9.0 +/- 3.0 cm/s, p <0.03). Tissue Doppler imaging RV early diastolic velocity (E wave) and the ratio of early to late diastolic velocities (E/A) also increased significantly after levosimendan administration (p <0.01 and p <0.05, respectively). Systolic pulmonary arterial pressure decreased significantly (54 +/- 11 vs 43 +/- 11 mm Hg, p <0.01) in the levosimendan-treated patients. Levosimendan beneficially modulated neurohormonal and inflammatory status by decreasing B-type natriuretic peptide levels (p <0.05) and by altering the ratio of interleukin-6 to interleukin-10 in favor of the latter (p <0.05). In conclusion, levosimendan could offer further therapeutic advantages in patients with advanced heart failure by improving systolic and diastolic RV function.