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.

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.

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.

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.

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.

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.

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.

Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper.

Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps.

Urine proteome analysis in heart failure with reduced ejection fraction complicated by chronic kidney disease: feasibility, and clinical and pathogenetic correlates.

AIMS: Urine proteome analysis (UPA) has already provided accurate discriminatory patterns of urinary peptides for renal disease, coronary artery disease, and asymptomatic LV diastolic dysfunction. UPA has now been used to characterize a discriminatory peptide biomarker pattern and establish a diagnostic classifier for heart failure patients with reduced ejection fraction (HFrEF) in the presence of chronic kidney disease (CKD). METHODS AND RESULTS: We analysed the urine proteome profiles obtained by capillary electrophoresis online coupled to micro-TOF (time of flight) mass spectrometry of 126 individuals, 59 HFrEF patients and 67 controls matched for age, sex, and renal function. In total, 107 significant discriminatory peptides were identified and used to establish a support vector machine-based classifier that was successfully applied to a test set of 25 HFrEF patients and 33 controls, achieving 84% sensitivity and 91% specificity. The majority of sequenced peptides were fragments of collagen type I and III. CONCLUSION: UPA was able to identify a set of HFrEF-specific urinary peptide biomarkers on a background of CKD that were successfully utilized to establish a syndrome's classifier.

Efficacy and safety of functional electrical stimulation of lower limb muscles in elderly patients with chronic heart failure: A pilot study.

BACKGROUND: Exercise training is an established modality in chronic heart failure. Functional electrical stimulation (FES) is an effective alternative mode of training in patients unwilling or unable to exercise; however, it has not been investigated in elderly patients. We sought to investigate the effects of FES on functional status, quality of life, emotional status and endothelial function in chronic heart failure patients aged 70 years or higher. METHODS: Thirty patients with stable systolic chronic heart failure (mean age 75 ± 3 years, New York Heart Association (NYHA) class II/III, 37%/63%) randomly underwent a six-week FES training programme or placebo. 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 endothelial function (flow-mediated dilatation) were assessed at baseline and upon protocol completion. RESULTS: A significant improvement in NYHA class (p=0.005), KCCQ-functional (F=68.6, p for interaction<0.001), KCCQ-overall (F=66.9, p<0.001), BDI (F=66.3, p<0.001) and Zung SDS (F=95.1, p<0.001) was observed in the FES group compared to placebo. Patients in the FES group also had a significant increase in flow-mediated dilatation compared with placebo (F=59.1, p<0.01). FES-induced per cent change in flow-mediated dilatation was significantly correlated with respective per cent change in KCCQ functional (r=0.386, p=0.039). CONCLUSION: In this pilot study, FES effectively improved functional status, quality of life, motional stress and endothelial function in elderly chronic heart failure patients and warrants further investigation in this particular group of patients.

Clinical and prognostic implications of plasma NGAL and NT-proBNP in adult patients with congenital heart disease.

BACKGROUND: Prognostic value of NT-proBNP is well established in patients with congenital heart disease. Growing evidence suggests that plasma NGAL is elevated in heart failure but data is limited in congenital heart disease. This study investigates the combined prognostic value of plasma NGAL with plasma NT-proBNP in adult patients with congenital heart disease. METHODS: Plasma levels of NT-proBNP and NGAL were measured in 76 consecutive adult patients (33 men, mean age 31.7 ± 14 yrs) with congenital heart disease and normal values of serum creatinine. Patients were divided in three groups: A: simple cardiac lesions, B: complex cardiac lesions and C: cyanotic lesions. Patients were also monitored for long-term major cardiovascular events: death, hospitalization, NYHA class worsening, new onset of arrhythmias, surgical or percutaneous intervention. RESULTS: NGAL value was significantly different between groups: In group A median NGAL value was 64.5 ± 36.7 ng/ml, in group B median NGAL value was 88.77 ± 36.17 ng/ml and in group C median NGAL value was 121 ± 40 ng/ml (group A vs. group B: p = 0.048, group B vs. group C: p = 0.037, group A vs. group C: p = 0.003). Plasma NT-proBNP predicted all events (HR = 1.001, CI = 1.001-1.002, p = 0.0006) as well as cardiovascular death alone (HR = 1.001, CI = 1.001-1.002, p = 0.0004); plasma NGAL was the only predictor of cardiovascular death (HR = 1.017, CI = 1.001-1.033, p = 0.037). CONCLUSION: Plasma NGAL levels were lower in patients with simple congenital disease compared to patients with complex congenital heart disease and cyanotic congenital heart disease. Plasma NGAL levels correlated with NT-proBNP and could predict cardiovascular death in this small cohort of patients.