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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 [mu]mol/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. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effects of carvedilol therapy on left atrial (LA) function in patients with heart failure from nonischemic dilated cardiomyopathy. Methods and Results: Thirty-five patients (42.4 +/- 13.5 years) in New York Heart Association functional Class II-III have been studied. A low-dose (20 mug.kg.min) echo-dobutamine study has been performed, before and 12 months after carvedilol therapy. Twelve months after carvedilol therapy, a significant improvement in LA and left ventricular (LV) function was observed. To investigate the beneficial effects of carvedilol, patients were separated into 2 groups according to the presence of pretreatment LV contractile reserve (CR) (ejection fraction [EF] increases >20% after dobutamine infusion): Group A consisted of 18 patients with CR and Group B of 17 patients without CR. After carvedilol treatment, both the LV and LA function were improved in group A (P < .01 for all). However, in group B, only the LA function was significantly improved (left atrial ejection volume increased from 10.4 +/- 3 mL to 15.4 +/- 6.7, P < .01 and LA ejection fraction from 19.6 +/- 45.3% to 29.4 +/- 12.5%, P < .01), whereas the LV contractile reserve has partially reappeared (EF from 29.9 +/- 4.5% at baseline, increased after dobutamine infusion to 35.8 +/- 6.8%, P < .0001). Conclusions: In conclusion, carvedilol therapy is associated with improvement in both LV and LA functions in nonischemic dilated cardiomyopathy. In a subgroup of these patients, carvedilol may act differently on LV and LA function. [ABSTRACT FROM AUTHOR]

Levosimendan reduces symptoms and improves hemodynamics in patients with acutely decompensated chronic heart failure (ADCHF). The aim of this study was to investigate (1) the association of changes induced by low-dose dobutamine stress echocardiography in 2-dimensional strain parameters with the corresponding changes in the left ventricular (LV) ejection fraction (EF) and LV outflow tract velocity time integral (VTI) in patients with ADCHF and (2) whether LV contractile reserve assessed by conventional and speckle-tracking echocardiography is associated with clinical and neurohumoral improvement after levosimendan treatment. Twenty-eight consecutive patients with ADCHF (mean age 65 +/- 10 years, mean New York Heart Association class 3.6 +/- 0.3, mean EF 22 +/- 6%) were studied using dobutamine stress echocardiography before 24-hour infusion of levosimendan. The LV EF, VTI, and mean longitudinal, circumferential, and radial strain and strain rate using speckle-tracking imaging were measured. Twenty-one patients (75%) had evidence of contractile reserve (LV EF increase >10% and VTI increase >20% after peak dobutamine dose). Patients with versus without contractile reserve demonstrated greater improvements in New York Heart Association class (mean change -1.0 +/- 0.5 vs -0.5 +/- 0.3, p = 0.01) and reductions in B-type natriuretic peptide levels (-34 +/- 30% vs +4 +/- 31%, p <0.01) 48 hours after treatment. On multivariate analysis, mean longitudinal systolic strain rate reserve (peak longitudinal strain rate minus longitudinal strain rate at rest) was the best predictor of improvement in New York Heart Association class (p = 0.039) and B-type natriuretic peptide level (p = 0.042) after levosimendan among the reserve of LV fractional shortening, the EF, VTI, and longitudinal, circumferential, and radial strain and strain rate. In conclusion, dobutamine-induced changes in longitudinal systolic strain rate are associated with clinical and neurohumoral improvement after levosimendan treatment in patients with ADCHF. [ABSTRACT FROM AUTHOR]

Background : Atrial fibrillation (AF) is a common arrhythmia in the emergency department (ED). We investigated the role of N-terminal pro b-type natriuretic peptide (NT-proBNP) in predicting both the outcome of AF cardioversion and the risk of AF recurrence or persistence on the 8th (D8) and 30th (D30) day post-cardioversion. Methods : This prospective, observational study evaluated patients with recent-onset AF, managed by either pharmacological (PC) or electrical cardioversion (EC) in the ED. Patients were treated either immediately or electively after 3 weeks of anticoagulation. NT-proBNP assessments were performed prior to cardioversion. Results : Of the 148 patients enrolled, 56% had paroxysmal AF, 85% underwent immediate cardioversion and 72% received EC. Successful cardioversion to sinus rhythm (SR) was achieved in 85% of patients. Patients with successful cardioversion and those who remained free from AF on D8 had lower NT-proBNP levels compared to patients with failed cardioversion or with AF recurrence or persistence on D8 [day of cardioversion, D0: SR vs. non-SR, 387 (127-1095) pg/mL vs. 1262 (595-2295), p = 0.004; D8: SR vs. non-SR, 370 (127-1095) vs. 1366 (718-2295), p = 0.002]. In multivariate analysis, higher logNT-proBNP was associated with higher risk of cardioversion failure [OR, 95%CI: 4.80 (1.58-14.55), p = 0.006] and AF recurrence or persistence on D8 [OR, 95%CI: 3.65 (1.06-12.59), p = 0.041]. ROC analysis confirmed the predictive ability of NT-proBNP for both outcomes (D0: AUC 0.735, p < 0.001; D8: AUC 0.761, p < 0.001). A cut-off value of NT-proBNP > 580 pg/mL was able to predict failure of AF conversion and occurrence of recurrent/persistent AF at D8. Conclusions : NT-proBNP is a promising biomarker for identifying patients presenting to the ED with recent-onset AF who run a greater risk of cardioversion failure and post-discharge AF recurrence/persistence in the immediate and short term.

Background/Objectives: Transthyretin amyloid (ATTR) cardiomyopathy mimics left ventricular hypertrophy (LVH) and has been identified as a specific cause of heart failure (HF). The aim of this study was to assess the prevalence of ATTR among patients presenting to the Emergency Department (ED) with acute HF (AHF) and LVH and explore their clinical characteristics and outcomes. Methods: Of 127 AHF patients with LVH, 95 completed the diagnostic protocol, which included monoclonal paraprotein testing and technetium-99 m pyrophosphate scintigraphy. Patients were followed for 6 months, and adverse events, including mortality and HF-related hospitalizations, were recorded. Results: ATTR was diagnosed in 8.4% of patients. The mean left ventricular ejection fraction (EF) was 46 ± 7% in ATTR subjects, with 25% classified as HF with reduced EF, 37.5% HF with mildly reduced EF, and 37.5% HF with preserved EF. N-terminal pro b-type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hs-TnT) were higher in ATTR compared to the non-ATTR group [NT-proBNP: 5863 (6519-12382) pg/mL versus 3586 (1393.5-6322) pg/mL, p = 0.007; hs-TnT: 35.9 (47.9-83.8) pg/mL versus 30.0 (19.4-49.5) pg/mL, p = 0.0006]. During follow-up, twenty-three patients from the cohort died: six in the ATTR and seventeen in the non-ATTR group. The estimated survival rate was significantly lower in ATTR versus non-ATTR patients (log-rank p < 0.0001). Conclusions: In this cohort of AHF patients with LVH presenting to the ED, ATTR cardiomyopathy was detected in 8.4%. Using routinely used cardiac biomarkers and basic echocardiography allows for the raising of suspicion of the disease from the ED setting, potentially facilitating earlier diagnosis in this population.

Objective: Observational studies have shown that the management of patients with cardiogenic shock (CS) by dedicated multidisciplinary teams improves clinical outcomes. Nevertheless, these studies reflect a specific organizational setting with most patients being transferred from referring hospitals, hospitalized in cardiac intensive care units (ICU), or treated with mechanical circulatory support (MCS) devices. The purpose of this study was to document the organization and outcomes of a CS team offering acute care in an all-comer population., Methods: A CS team was developed in a large academic tertiary institution. The team consisted of emergency care physicians, critical care cardiologists, interventional cardiologists, cardiac surgeons, ICU physicians, and heart failure specialists and was supported by a predefined operating protocol, a dedicated communication platform, and regular team meetings., Results: Over 12 months, 70 CS patients (69 ± 13 years old, 67% males) were included. Acute myocardial infarction (AMI-CS) was the most common cause (64%); 31% of the patients presented post-resuscitated cardiac arrest and 56% needed invasive mechanical ventilation (IMV). Coronary angiography was performed in 70% and 53% had percutaneous coronary intervention. MCS was used in 10% and 6% were referred for urgent cardiac surgery. The in-hospital mortality in our center was 40% with 39% of the patients dying within 24 h from presentation. Overall, 76% of the live patients were discharged home., Conclusion: Across an all-comer population, AMI was the most common cause of CS. A significant number of patients presented post-cardiac arrest, and the majority required IMV. Mortality was high with a significant number dying within hours of presentation., Competing Interests: Conflicts of interest Nothing to declare., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Introduction: B-blockers are regarded as beneficial pharmacologic agents in cardiac care, but their role in the acute setting remains ambiguous. Increasing evidence supports the important role of landiolol in critical care, a highly cardioselective intravenous b-blocker with rapid onset of action and short elimination time. Among its most valuable properties, which may aid to overcome special reservations related to b-blocker therapy in the acute setting, landiolol has a potent negative chronotropic effect while at the same time it exhibits a mild negative inotropic effect., Areas Covered: This expert opinion review aims to present basic pharmacologic aspects of landiolol and provide current clinical research focused on its efficacy and safety., Expert Opinion: Landiolol is a valuable and safe pharmacologic agent in acute cardiac care. Japanese and European guidelines have incorporated its use for the management of atrial tachyarrhythmia in patients with cardiac dysfunction. Although emerging clinical trials have experimented its use in patients with sustained ventricular tachycardia/fibrillation, acute myocardial infarction undergoing primary percutaneous intervention and in patients with septic cardiomyopathy, more studies are needed in order to establish its value in such cardiac conditions.

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., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Pathological interplay between the heart and kidneys is widely encountered in heart failure (HF) and is linked to worse prognosis and quality of life. Inotropes, along with diuretics and vasodilators, are a core medical response to HF but decompensated patients who need inotropic support often present with an acute worsening of renal function. The impact of inotropes on renal function is thus potentially an important influence on the choice of therapy. There is currently relatively little objective data available to guide the selection of inotrope therapy but recent direct observations on the effects of levosimendan and milrinone on glomerular filtration favour levosimendan. Other lines of evidence indicate that in acute decompensated HF levosimendan has an immediate renoprotective effect by increasing renal blood flow through preferential vasodilation of the renal afferent arterioles and increases in glomerular filtration rate: potential for renal medullary ischaemia is avoided by an offsetting increase in renal oxygen delivery. These indications of a putative reno-protective action of levosimendan support the view that this calcium-sensitizing inodilator may be preferable to dobutamine or other adrenergic inotropes in some settings by virtue of its renal effects. Additional large studies will be required, however, to clarify the renal effects of levosimendan in this and other relevant clinical situations, such as cardiac surgery., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.)

Cardiogenic shock (CS) is increasingly recognized in patients with malignancies, while cancer is independently associated with worse prognosis in CS. A number of conditions may lead to CS in cancer, including acute coronary syndromes, cardiomyopathy, takotsubo syndrome, myocarditis, pulmonary embolism, tamponade, and cardiac herniation. In these conditions, CS may be related to cancer itself or to cancer therapy, including surgery, chemotherapy, or radiotherapy. Given the significantly improved overall survival of patients with malignancies, the early recognition and proper management of CS in cancer become increasingly important. In the present paper, we review the available evidence on CS in patients with malignancies and highlight issues related to its management.

As a calcium sensitizer and inodilator that augments cardiac contractility without increasing myocardial oxygen demand or exacerbating ischaemia, levosimendan may be well configured to deliver inotropic support in cases of acute heart failure (AHF). Other factors favouring levosimendan in this setting include its extended duration of action due to the formation of an active metabolite and the lack of any attenuation of effect in patients treated with beta-blockers. Effects of levosimendan on systemic haemodynamics include its significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in right and left ventricular filling and total peripheral resistance. Rapid and sustained reduction in levels of natriuretic peptides is a consistent effect of levosimendan use and potentially favourable effects on other neurohormonal indicators of cardiac distress are also observed. Levosimendan has repeatedly been shown to be effective in relief of symptoms of AHF, notably dyspnoea and fatigue, while mortality data from clinical trials and registries suggest that levosimendan is markedly less likely than catecholaminergic inotropes to worsen prognosis. The vasodilator pharmacology of levosimendan is also pertinent to the drug's use in AHF, in which setting organ under-perfusion is often a key pathology. These considerations suggest that levosimendan may have a more favourable impact on the circumstances of the majority of AHF patients than adrenergic agents that act only or primarily as cardiac stimulants. They also suggest that levosimendan may advantageously be integrated into a comprehensive strategy of early intervention designed and intended to prevent cardiac destabilization worsening to the point where hospitalization is necessary. Levosimendan should be used with caution and with tightened haemodynamic monitoring in patients who have low baseline blood pressure (systolic blood pressure <100 mmHg; diastolic blood pressure <60 mmHg), or who are at risk of a hypotensive episode.

Sacubitril/valsartan is a novel, first-in-class drug, which combines a neprilysin inhibitor with an angiotensin receptor blocker. Sacubitril inhibits neprilysin endopeptidase, blocking the catabolism of natriuretic peptides (NP), thereby increasing their bioavailability. Valsartan counterbalances the increase of angiotensin II that results from neprilysin inhibition, exerting also the beneficial effects of angiotensin receptor blockers seen in previous HF trials. PARADIGM-HF trial has proved the superiority of sacubitril/valsartan (LCZ696) over ACE inhibitor enalapril to reduce mortality and morbidity of symptomatic HF patients with reduced ejection fraction (HFrEF), setting the grounds for the replacement of ACE inhibitors by sacubitril/valsartan in the management of HFrEF. Sacubitril/valsartan is currently being tested in a phase III trial (PARAGON-HF) in patients with HF with preserved EF. PARAGON-HF is also expected to provide further data regarding the long-term safety of sacubitril/valsartan, hopefully to alleviate concerns regarding the effects of neprilysin inhibition on cognitive function.

Acute heart failure (AHF) in the elderly is an increasingly common clinical problem associated with high in-hospital, short- and long-term mortality rates worldwide. Elderly patients with AHF have different clinical and pathophysiological profiles compared with younger ones. Prevalent cardiovascular comorbidities in the elderly are arterial hypertension and atrial fibrillation, whereas ischemic heart disease and associated risk factors are more common in younger patients. There is a need for greater dissemination of heart failure guidelines and for involvement of multidisciplinary teams for optimizing treatment and eliminating disparities in care in this vulnerable patient group across both sides of the Atlantic., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim-Methods: ALARM-HF was a retrospective, observational registry that included 4,953 patients admitted for acute heart failure (AHF) in six European countries, Turkey, Mexico and Australia. Data about respiratory disorders and related medications were available for 4,616 patients with AHF., Results: Chronic obstructive pulmonary disease (COPD) patients (n = 1,143, 24.8%) were older and more frequently men (p < 0.001) when compared to non-COPD patients. Despite the equivalent left ventricular ejection fraction (38.6 ± 13.7 vs. 38.2 ± 14.5%, p > 0.05), COPD patients more frequently presented with acutely decompensated heart failure (p < 0.001). Moreover, a worse cardiovascular profile was observed in the COPD group, including more atrial fibrillation/flutter, diabetes, hypertension, obesity, peripheral vascular disease (p < 0.001). Before admission, a higher percentage of COPD patients had experienced infections (25.0 vs. 14.0 %, p < 0.001), and were more likely to receive diuretics (p = 0.006), ACE inhibitors (p = 0.042), nitrates (p = 0.003), and digoxin (p = 0.034). With the exception of ACE inhibitors, those differences maintained at discharge, with concomitant increase in ARBs prescription (p = 0.01). Notably, β-blockers were less prescribed before admission (21.1 vs. 23.8%, p = 0.055) in COPD patients, and remained underutilized at discharge (p < 0.001). Correcting for baseline differences, all-cause in-hospital mortality did not differ between COPD and non-COPD groups (10.1 vs. 10.9%, p = 0.085)., Conclusion: A large proportion of AHF patients presented with concomitant COPD, had different clinical characteristics/co-morbidities, and less frequently received evidence-based pharmacological therapy compared to non-COPD patients. However, the in-hospital mortality was not higher in COPD group.

Aims: The aim of this study was to determine whether intermittent ambulatory treatment with levosimendan would improve functional capacity, quality of life, and event-free survival in patients with advanced heart failure., Methods and Results: This was a prospective, randomized, double-blind, placebo-controlled, multicentre, parallel-group trial of pulsed infusions of levosimendan in 120 outpatients with advanced heart failure (EF ≤35%, NYHA class III or IV). The study was conducted at 11 centres in Austria, Greece, and Germany. Levosimendan (0.2 µg/kg/min) or placebo was administered for 6 h at 2-week intervals over 6 weeks, in addition to standard care therapy. The primary outcome was the proportion of patients with a ≥20% improvement in the 6 min walk test and a ≥15% score increase on the Kansas City Cardiomyopathy Questionnaire at the end of the 24-week study period. Secondary outcomes included event-free survival after 24 weeks. Analyses were performed on an intention-to-treat basis. The primary endpoint was reached in 19% of patients receiving levosimendan and 15.8% of patients receiving placebo (odds ratio 1.25; 95% confidence interval 0.44-3.59; P = 0.810). Cardiac death (four vs. one), heart transplants (two vs. one), and acute heart failure (14 vs. nine) were more frequent with placebo as compared with levosimendan. The incidence of side effects was comparable between groups., Conclusion: Intermittent ambulatory treatment with levosimendan in patients with advanced heart failure did not improve significantly functional capacity or quality of life as compared with placebo. An adequately powered, event-driven trial is warranted to enlarge on our findings., Trial Registration: NCT01065194., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Background and Purpose: Proximal aortic plaques, especially in the aortic arch, have already been established as an important cause of stroke and peripheral embolism. However, aortic plaques situated in the descending thoracic aorta have recently been postulated as a potential embolic source in patients with cryptogenic cerebral infarction through retrograde aortic flow. The aim of the present study was to evaluate the potential association of descending aorta atheromatosis with cerebral ischemia., Methods: We conducted a systematic review and meta-analysis of all available prospective observational studies reporting the prevalence of complex atheromatous plaques in the descending aorta in patients with stroke and in unselected populations undergoing examination with transesophageal echocardiography., Results: We identified 11 eligible studies including a total of 4000 patients (667 patients with stroke and 3333 unselected individuals; mean age, 65 years; 55% men). On baseline transesophageal echocardiograpic examination, the prevalence of complex atheromatous plaques in the descending aorta was higher (P=0.001) in patients with stroke (25.4%; 95% confidence interval, 14.6-40.4%) compared with unselected individuals (6.1%; 95% confidence interval, 3.4-10%). However, no significant difference (P=0.059) in the prevalence of complex atheromatous plaques in the descending aorta was found between patients with cryptogenic (21.8%; 95% confidence interval, 17.5-26.9%) and unclassified (28.3%; 95% confidence interval, 23.9-33.1%) cerebral infarction., Conclusions: Our findings indicate that the presence of complex plaques in the descending aorta is presumably a marker of generalized atherosclerosis and high vascular risk. The present analyses do not provide any further evidence for a direct causal relationship between descending aorta atherosclerosis and cerebral embolism., (© 2014 American Heart Association, Inc.)

Aim: Temporal trends of epidemiological data on acute heart failure (AHF) are limited. We sought to assess changes in epidemiology, clinical presentation and management of AHF in Greece using data from two international registries conducted three years apart., Methods and Results: The Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF) and the European Society of Cardiology-Heart Failure (ESC-HF) pilot survey were conducted during 2006-2007 and 2009-2010, respectively. A total of 432 AHF patients were recruited by Greek sites in the two registries (255 in ALARM-HF and 177 in ESC-HF pilot survey). About 60% of patients in both registries presented with acutely decompensated chronic HF and 40% with de novo AHF. The use of life-prolonging, guideline-recommended medications increased over time (pre-admission use of angiotensin-converting enzyme (ACE) inhibitors/ angiotensin receptor blockers (ARBs) from 47% to 60%, beta-blockers from 31% to 65%, aldosterone antagonists from 18% to 45%). Those therapies also increased during hospitalisation in both registries. Patients were treated by cardiologists in >90% of cases during hospitalisation; the main intravenous therapies in both registries were diuretics (94% and 97%), followed by vasodilators (47% and 22%) and inotropes (31% and 20%). The length of hospitalisation remained similar (6-7 days in both registries), while in-hospital mortality dropped from 8.5% in the ALARM-HF to 4.5% in the ESC-HF pilot survey., Conclusions: A temporal increase in the use of life-prolonging therapies along with an improvement of in-hospital mortality was observed. Clinical profiles, in-hospital management and outcome of AHF patients in Greece were similar to other European countries, despite regional differences in healthcare systems.

Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial KATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).

Background: High-sensitivity troponin Τ (hs-TnΤ) allows the detection of very minor myocardial injury and has emerged as a novel prognostic marker in patients with cardiovascular disease. The aim of the present study was to determine the prognostic utility of hs-TnΤ levels in patients admitted to hospital for acutely decompensated heart failure (ADHF) and non-detectable conventional TnΤ levels., Methods: We prospectively enrolled 113 consecutive ADHF patients [77 (68%) men], mean age: 72.7±11.3 years, presented at admission with normal (<0.03 ng/ml) conventional (4th generation) TnΤ levels. Hs-TnΤ levels were measured by relevant commercially available kits and patients were monitored for major adverse events during a median follow-up period of 174 days (94-728 days)., Results: In the univariate Cox proportional hazard analysis, hs-TnΤ was significantly related to death (HR=1.002 with 95%: confidence interval (CI) 1.001-1.003, P=0.001). In multivariate analysis, it remained a significant predictor of death after adjustment for age, gender, ejection fraction and creatinine levels (HR=1.003 with 95%: CI 1.001-1.005, P=0.008)., Conclusion: hs-TnΤ seems to identify high risk patients hospitalized for ADHF, independently of other classical prognostic biomarkers. Further studies are necessary to confirm the utility of this novel biomarker in risk stratification and management of patients with ADHF., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Functional electrical stimulation (FES) improves exercise capacity, quality of life, emotional stress, and endothelial function in chronic heart failure with impaired systolic function. We sought to investigate the effects of FES on the above parameters in patients with preserved ejection fraction (HFpEF)., Methods: Thirty HFpEF patients, 18 female and 12 male, aged 69 ± 8 years, in New York Heart Association class II or III and with mean ejection fraction 63% ± 6%, were randomly (1:1) assigned to a 6-week FES program or placebo. Assessment was performed at baseline and after completion of training protocol and included 6-minute walked distance, quality of life (Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire), depressive symptoms (Beck Depression Inventory and Zung self-rated depression scores), B-type natriuretic peptide, endothelial function (flow-mediated dilatation), and left ventricular diastolic function., Results: A significant improvement in 6-minute walked distance (F = 21.61, P = .001), Kansas City Cardiomyopathy Questionnaire summary (F = 8.68, P = .006), Minnesota Living with Heart Failure Questionnaire (F = 6.43, P = .017), Beck Depression Inventory (F = 6.66, P = .015), Zung (F = 6.25, P = .019), and flow-mediated dilatation diameter (F = 11.98, P = .002) was observed in the FES group compared with placebo group; B-type natriuretic peptide also declined but not significantly (F = 0.249, P = .622), and there was a tendency toward lower mitral E/e' wave ratio (F = 3.066, P = .091)., Conclusion: As in heart failure and reduced left ventricular ejection fraction, FES also improves exercise capacity, quality of life, emotional status, and endothelial function in HFpEF. Given the lack of effective evidence-based therapies in these patients, FES warrants further investigation., (© 2013.)

Aims: Hypothalamic axis deregulation is associated with clinical severity and depression in chronic heart failure (CHF). We investigated the relationship of serum prolactin, an indicator of hypothalamic axis function, to neurohomonal/immune activation and depressive symptoms in CHF as well as its prognostic value., Methods and Results: Serum prolactin was determined in 180 patients with advanced CHF (aged 65 ± 12 years, mean LVEF 27 ± 7%) along with natriuretic peptides (BNP), inflammatory cytokines, endothelial adhesion molecules, 6 min walk test (6MWT), and the Zung self-rating depression scale (SDS). Patients were followed for all-cause death or hospitalization for cardiovascular reasons for up to 8 months. Prolactin levels were significantly correlated with NYHA class (r = 0.394, P < 0.001), LVEF (r = -0.314, P < 0.001), 6MWT (r = -0.353, P < 0.001), BNP (r = 0.374, P < 0.001), Zung SDS (r = 0.544, P < 0.001), interleukin-6 (IL-6) (r = 0.451, P < 0.001), IL-10 (r = -0.426, P < 0.001), tumour necrosis factor (TNF)-α (r = 0.310, P = 0.001), soluble Fas (r = 0.333, P < 0.001), soluble Fas-ligand (r = 0.517, P < 0.001), soluble intercellular adhesion molecule-1 (ICAM-1) (r = 0.409, P < 0.001), and soluble vascular cell adhesion molecule-1 (VCAM-1) (r = 0.480, P < 0.001). During follow-up, 119 patients (66%) died or were hospitalized for cardiovascular events after a median time of 72 days (range 5-220 days); these patients had higher baseline prolactin levels (10.2 ± 5.7 vs. 6.7 ± 4.3 ng/mL, P < 0.001), and a prolactin value ≥4.5 ng/mL was associated with a higher rate of death or hospitalization (116 ± 7 vs. 181 ± 11 days, P = 0.0001). In multivariate analysis, prolactin levels remained an independent predictor of death or hospitalization (<4.5 vs. ≥4.5 ng/mL; odds ratio, 0.368; 95% confidence interval 0.148-0.913; P = 0.031), along with BNP (P < 0.001) and 6MWT (P = 0.020)., Conclusions: Serum prolactin is associated with neurohormonal/immune activation and depressive symptoms and is an independent predictor of prognosis in advanced CHF.

Aim and Methods: Gender-related differences in clinical phenotype, in-hospital management and prognosis of acute heart failure (AHF) patients have been previously reported in European and US registries. The ALARM-HF survey is the first to include a cohort of 4953 patients hospitalized for AHF in 666 hospitals in 6 European countries, Mexico and Australia., Results: Women accounted for 37% of the study population, were older and had higher rates of de novo heart failure (45% vs 36%, p<0.001) than men. An acute coronary syndrome (ACS) was the predominant precipitating factor in both genders, but to a lesser extent in females (30% vs 42%, p<0.001). Between genders comparison showed higher incidence of atrial fibrillation, valvular heart disease, diabetes, obesity, anemia and depression in women (p<0.05). Similarly, women had higher left ventricular ejection fraction (LVEF) on admission (42 ± 15% vs 36 ± 13%, p<0.001) and systolic blood pressure (135 ± 40 mm Hg vs 131 ± 39 mm Hg, p=0.001) than men. On the other hand, men had more often coronary artery disease, renal failure and chronic obstructive pulmonary disease (p<0.05). Importantly, in-hospital mortality was similar in both genders (11.1% in females vs 10.5% in males, p=0.475), and its common predictors were: systolic blood pressure at admission, creatinine>1.5mg/dL and diabetes. Furthermore, recent ACS, valvular heart disease and dementia contributed to prognosis in women, while LVEF, hypertension and anemia were independent predictors in men., Conclusion: Among patients with AHF, there are significant differences in co-morbidities, precipitating factors and predictors of in-hospital mortality between genders. Nevertheless, in-hospital mortality remains similar between genders., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Sleep disordered breathing (SDB) is highly prevalent in patients with chronic heart failure (CHF) and is associated with adverse effects on cardiac geometry and function. Continuous positive airway pressure (CPAP) has been proved an effective treatment modality for obstructive sleep apnoea (OSA), whereas adaptive servoventilation (ASV) is more effective in patients with central sleep apnoea (CSA). The impact of selection of therapy and effective apnoea alleviation on cardiac performance and reverse left ventricular remodelling (r-LVR) has not yet been evaluated., Methods: Eighty five patients with stable CHF were screened for SDB and underwent polysomnography and treatment according to the type of SDB. Clinical evaluation and a comprehensive echocardiographic study was performed before initiation of therapy and after six months of effective treatment (ventilator use >5h/day with AHI <5 events/h)., Results: Seventeen compliant patients under effective treatment were included in the analysis (8 OSA under Autoset CPAP and 9 CSA under ASV). In both groups, a significant improvement in all measured, conventional and TDI LV systolic indexes was recorded, including LVEF (32% ± 6% vs. 27% ± 6%, p<0.001). A decrease in LV end-systolic volume (189 ± 94 ml vs. 211 ± 88 ml, p=0.015, difference >10%) was indicative of r-LVR. Furthermore, RV systolic parameters were also increased (TAPSE, p<0.001; systolic TDI wave from lateral tricuspid annular aspect, p=0.001), whereas right heart dimensions and areas were diminished, indicating better pulmonary haemodynamics. Moreover, a significant improvement in patients' clinical status, as evaluated by New York Heart Association Class was also documented at the end of six months follow-up., Conclusions: Effective alleviation of SDB in CHF patients is associated with significant improvements in LV and RV systolic function and r-LVR. Longitudinal studies are needed to evaluate effects on morbidity and mortality., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Renal dysfunction is highly prevalent in patients with acute heart failure (AHF). These patients are more vulnerable in worsening of kidney function and have also higher mortality rates., Areas Covered: Recent developments in the understanding of bidirectional interaction between heart and kidney are reviewed in the context of the potential impact of inotropes on renal function. Key clinical trials reporting the use of inotropes in AHF patients with renal dysfunction are discussed in this review., Expert Opinion: Inotropes may be indicated on a short-term basis and under close monitoring in AHF with renal dysfunction mostly in cases of low output heart failure that can provoke renal hypoperfusion. Dopamine administration with low dose of i.v. furosemide has been recently compared with high dose of i.v. furosemide alone, demonstrating lower rates of worsening renal function and electrolyte disturbances. Moreover, small clinical trials have shown that the novel inodilator levosimendan seems to be superior to dobutamine or placebo in improving renal function in patients with acutely decompensated heart failure. The impact of novel inotropes on kidney function is still unclear. Randomized clinical trials are required in order to identify the role of inotropes in the management and/or prevention of acute cardiorenal syndrome.

The molecular background of the Ca(2+)-sensitizing effect of levosimendan relates to its specific interaction with the Ca(2+)-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of ATP-sensitive sarcolemmal K(+) channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K(+) channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection. Finally, it has become evident, that levosimendan possesses an isoform-selective phosphodiesterase-inhibitory effect. Interpretation of the complex mechanism of levosimendan action requires that all potential pharmacological interactions are analyzed carefully in the framework of the currently available evidence. These data indicate that the cardiovascular effects of levosimendan are exerted via more than an isolated drug-receptor interaction, and involve favorable energetic and neurohormonal changes that are unique in comparison to other types of inodilators., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (FEV1/FVC <70%) are extensively used for diagnosis of chronic obstructive lung disease in heart failure (HF). The American Thoracic Society (ATS)/European Respiratory Society (ERS) recommends the use of age- and gender-specific lower limit of normal (LLN) for FEV1/FVC. We compared the impact of these definitions on apparent prevalence of airway obstruction in chronic HF., Methods: Standardized pre- and post-bronchodilator spirometry was performed in HF patients. Airway obstruction was defined by ATS/ERS criteria as diagnostic standard. Additionally, airway obstruction was calculated using the GOLD criteria., Results: Of the 89 participants who fulfilled the ATS criteria for acceptability and reproducibility, 24.7% met ATS/ERS and 43.8% GOLD criteria for airway obstruction (Chi-square p = 0.007, McNemar <0.001). Sensitivity of GOLD criteria was 100%, specificity 74.6%, positive predictive value 56.4% and negative predictive value 100%. Among all individuals with an FEV1/FVC > LLN, 25.4% were falsely identified when using the GOLD criteria. A majority of false positives qualified for airway obstruction GOLD stage I (FEV1% ≥80%), which was significantly less often observed among true positives (76.5 vs. 31.8%; p < 0.001). Only 31.8% of patients with irreversible airway obstruction detected by the ATS/ERS criteria reported a history of COPD., Conclusions: In all HF patients with persistent dyspnoea despite optimal HF treatment, spirometric testing should be performed. Application of the GOLD criteria leads to overdiagnosis of irreversible airway obstruction in patients with HF, which may result in inappropriate medical therapy and health-care decisions.

Objective/methods: ALARM-HF was an in-hospital observational survey that included 4953 patients admitted for acute heart failure (AHF) in six European countries, Mexico and Australia. This article is a secondary analysis of the survey which evaluates differences in clinical phenotype, treatment regimens and in-hospital outcomes in AHF patients with diabetes mellitus (DM) compared to non-diabetics. The data were collected retrospectively by the investigators, and the diagnosis of AHF (reported at discharge) was based on the definition and classification of ESC guidelines, while the diagnosis of DM was based on medical record (past medical and medication history)., Results: This sub-analysis demonstrates substantial differences regarding both baseline features and in-hospital outcome among diabetic and non-diabetic AHF patients. Diabetic patients (n=2229, 45%) presented more frequently with acute pulmonary edema (p<0.001) than non-diabetics, had more often acute coronary syndrome (p<0.001) as precipitating factors of AHF, and multiple comorbidities such as renal dysfunction (p<0.001), arterial hypertension (p<0.001), anemia (p<0.001) and peripheral vascular disease (p<0.001). All-cause in-hospital mortality of diabetics was higher compared to non-diabetics (11.7% vs 9.8%, p=0.01). The multivariate analysis revealed that older age (p=0.032), systolic blood pressure <100mm Hg (p<0.001), acute coronary syndrome and non compliance as precipitating factors (p=0.05 and p=0.005, respectively), history of arterial hypertension (p=0.022), LVEF<50% (p<0.001), serum creatinine >1.5mg/dl (p=0.029), absence of life saving therapies such as ACE inhibitors/ARBs (p<0.001) and beta-blockers (p=0.014) at admission, as well as absence of interventional treatment by PCI (p<0.001), were independently associated with adverse in-hospital outcome., Conclusion: Diabetics with AHF have higher in-hospital mortality than non-diabetics despite their intensive treatment regimens (regarding care for HF and ACS), possibly due to underlying ischemic heart disease and the presence of multiple comorbidities., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We performed a survey on acute heart failure (AHF) in nine countries in four continents. We aimed to describe characteristics and management of AHF among various countries, to compare patients with de novo AHF versus patients with a pre-existing episode of AHF, and to describe subpopulations hospitalized in intensive care unit (ICU) versus cardiac care unit (CCU) versus ward., Methods and Results: Data from 4,953 patients with AHF were collected via questionnaire from 666 hospitals. Clinical presentation included decompensated congestive HF (38.6%), pulmonary oedema (36.7%) and cardiogenic shock (11.7%). Patients with de novo episode of AHF (36.2%) were younger, had less comorbidities and lower blood pressure despite greater left ventricular ejection fraction (LVEF) and were more often admitted to ICU. Overall, intravenous (IV) diuretics were given in 89.7%, vasodilators in 41.1%, and inotropic agents (dobutamine, dopamine, adrenaline, noradrenaline and levosimendan) in 39% of cases. Overall hospital death rate was 12%, the majority due to cardiogenic shock (43%). More patients with de novo AHF (14.2%) than patients with a pre-existing episode of AHF (10.8%) (p = 0.0007) died. There was graded mortality in ICU, CCU and ward patients with mortality in ICU patients being the highest (17.8%) (p < 0.0001)., Conclusions: Our data demonstrated the existence of different subgroups based on de novo or pre-existing episode(s) of AHF and the site of hospitalization. Recognition of these subgroups might improve management and outcome by defining specific therapeutic requirements.

Acute heart failure (AHF) with preserved left ventricular ejection fraction (PLVEF) represents a significant part of AHF syndromes featuring particular characteristics. We sought to determine the clinical profile and predictors of in-hospital mortality in patients with AHF and PLVEF in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). This survey is an international observational study of 4,953 patients admitted for AHF in 9 countries (6 European countries, Mexico, and Australia) from October 2006 to March 2007. Patients with PLVEF were defined by an LVEF ≥ 45%. Of the total cohort, 25% of patients had PLVEF. In-hospital mortality was significantly lower in this subgroup (7% vs 11% in patients with decreased LVEF, p = 0.013). Candidate variables included demographics, baseline clinical findings, and treatment. Multivariate logistic regression analysis showed that the variables independently associated with in-hospital mortality included systolic blood pressure at admission (p <0.001), serum sodium (p = 0.041), positive troponin result (p = 0.023), serum creatinine >2 mg/dl (p = 0.042), history of peripheral vascular disease and anemia (p = 0.004 and p = 0.015, respectively), secondary (hospitalization for other reason) versus primary AHF diagnosis (p = 0.043), and previous treatment with diuretics (p = 0.023) and angiotensin-converting enzyme inhibitors (p = 0.021). In conclusion, patients with AHF and PLVEF have lower in-hospital mortality than those with decreased LVEF. Low systolic blood pressure, low serum sodium, renal dysfunction, positive markers of myocardial injury, presence of co-morbidities such as peripheral vascular disease and anemia, secondary versus primary AHF diagnosis, and absence of treatment with diuretics and angiotensin-converting enzyme inhibitors at admission may identify high-risk patients with AHF and PLVEF., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aims: Acute pulmonary oedema (APE) is the second, after acutely decompensated chronic heart failure (ADHF), most frequent form of acute heart failure (AHF). This subanalysis examines the clinical profile, prognostic factors, and management of APE patients (n = 1820, 36.7%) included in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF)., Methods and Results: ALARM-HF included a total of 4953 patients hospitalized for AHF in Europe, Latin America, and Australia. The final diagnosis was made at discharge, and patients were classified according to European Society of Cardiology guidelines. Patients with APE had higher in-hospital mortality (7.4 vs. 6.0%, P = 0.057) compared with ADHF patients (n = 1911, 38.5%), and APE patients exhibited higher systolic blood pressures (P < 0.001) at admission and higher left ventricular ejection fraction (LVEF, P < 0.01) than those with ADHF. These patients also had a higher prevalence of diabetes (P < 0.01), arterial hypertension (P < 0.001), peripheral vascular disease (P < 0.001), and chronic renal disease (P < 0.05). They were also more likely to receive intravenous (i.v.) diuretics (P < 0.001), i.v. nitrates (P < 0.01), dopamine (P < 0.05), and non-invasive ventilation (P < 0.001). Low systolic blood pressure (P < 0.001), low LVEF (<0.05), serum creatinine ≥1.4 mg/dL (P < 0.001), history of cardiomyopathy (P < 0.05), and previous cardiovascular event (P < 0.001) were independently associated with increased in-hospital mortality in the APE population., Conclusion: APE differs in clinical profile, in-hospital management, and mortality compared with ADHF. Admission characteristics (systolic blood pressure and LVEF), renal function, and history may identify high-risk APE patients.

Infection following the implantation of a left ventricular assist device (LVAD) is a life-threatening complication with mortality rates ranging from 15% to 44%. Staphylococcus aureus and Staphylococcus epidermidis are the most frequently identified pathogens and are responsible for 60% of LVAD-related infections, local as well as systemic. In this report we describe the successful therapeutic management of a patient who received a Heart Mate II as "bridging-to-recovery", which was complicated by device infection that was managed without device explantation.