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Εισαγωγή. Η αναιμία αποτελεί μια συχνή συνοσηρότητα της χρόνιας καρδιακής ανεπάρκειας με δυσμενή επίδραση στην πρόγνωση των ασθενών ενώ η βαρύτητα της έχει συσχετιστεί με την λειτουργική κλάση των ασθενών και με την ικανότητά τους για άσκηση. Οι ασθενείς με τελικού σταδίου καρδιακή ανεπάρκεια είναι επιρρεπείς στην ανάπτυξη σιδηροπενίας είτε μέσω μειονεκτικής απορρόφησης σιδήρου είτε μέσω αδυναμίας χρησιμοποίησης του από τον μυελό των οστών καθιστώντας την σιδηροπενία την πιο συχνή αιτία αναιμίας στην καρδιακή ανεπάρκεια. Παρά την αναγνώριση του ρόλου της αναιμίας ως προγνωστικού δείκτη, κατευθυντήριες οδηγίες ως προς την επιλογή και εφαρμογή θεραπευτικής στρατηγικής δεν έχουν θεσπιστεί. Σκοπός της παρούσας μελέτης είναι η σύγκριση της αποτελεσματικότητας του συνδυασμού ενδοφλέβιας χορήγησης σιδήρου με υποδόρια χορήγηση δαρμποετίνης Α έναντι της ενδοφλέβιας χορήγησης μόνο σιδήρου ως προς το βαθμό και τη ταχύτητα διόρθωσης της αναιμίας σε ασθενείς με τελικού σταδίου καρδιακή ανεπάρκεια και σιδηροπενική αναιμία. Μέθοδοι. 30 ασθενείς με τελικού σταδίου καρδιακή ανεπάρκεια και σιδηροπενική αναιμία τυχαιοποιήθηκαν σε εβδομαδιαία ενδοφλέβια χορήγηση σιδήρου και υποδόρια χορήγηση δαρμπεμποετίνης Α (300mg και 50 mcg αντίστοιχα, ομάδα A, ν=14) και σε εβδομαδιαία ενδοφλέβια χορήγηση σιδήρου (300mg, ομάδα B, ν=16). Η διάγνωση της σιδηροπενίας ετέθη από την εξέταση μυελικού επιχρίσματος Αποτελέσματα. Η μέση ηλικία των ασθενών στην Ομάδα Α ήταν 55,3±11 έναντι 59,1 ±12,3 έτη στην Ομάδα Β (P=ns). Η μέση τιμή της λειτουργικής κλάσης κατά ΝΥΗΑ, του κλάσματος εξωθήσεως ήταν 3,5±0,6 vs 3,1±0,1, 22,2±6,7 vs 25,6±6,7 % (P=ns) αντίστοιχα για τις δύο ομάδες ενώ η μέση τιμή αιμοσφαιρίνης, φερριτίνης και κρεατινίνης ορού κατά την έναρξη της θεραπείας ήταν 10,6±0,9 vs 10,9±1,1gr/dl , 121,1±114,2 vs 139,8±163,9 ng/lt και 1,3±0,5 vs 1,4±0,5 mg/dl (P=ns) για τις δύο ομάδες αντίστοιχα. Σημαντική και παρόμοια αύξηση της τιμής της αιμοσφαιρίνης παρατηρήθηκε από την δεύτερη εβδομάδα θεραπείας και στις δύο ομάδες [ομάδα A: 10,6±0,9 vs 11,2±1,1 gr/dl (p =0,013), ομάδα B: 10, 6±0, 9 vs11, 2±1,1gr/dl (p =0,013)]. Τρεις μήνες μετά την ολοκλήρωση της θεραπείας η τιμή της αιμοσφαιρίνης παραμένει αυξημένη στον ίδιο βαθμό και στις δυο ομάδες.[ομάδα A: 13±1,1vs12,9±0,7gr/dl (p=0,898), ομάδα B: 12, 6±1vs13,2±0,6gr/dl (p=0,093)] Συμπέρασμα. Η ενδοφλέβια χορήγηση σιδήρου είναι εξίσου αποτελεσματική θεραπεία ως προς την ταχύτητα και τον βαθμό διόρθωσης της αναιμίας σε ασθενείς με σιδηροπενική αναιμία και καρδιακή ανεπάρκεια με τον συνδυασμό σιδήρου και δαρμποετίνης Α .

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but several develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from C-reactive protein, D-dimer, interleukin-6, and ferritin circulating concentrations at hospitalization during the SAVE-MORE study, offers comparable predictive accuracy for progression to SRF or death within 14 days as suPAR ≥6 ng/ml (area under receiver operator characteristic curve, 0.81 for both). SCOPE score was validated against an independent dataset from the SAVE study. The SCOPE score is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions. Funding: The study was funded in part by the Hellenic Institute for the Study of Sepsis and by Swedish Orphan Biovitrum. The Hellenic Institute for the Study of Sepsis is the Sponsor of the SAVE and SAVE-MORE studies. Declaration of Interests:E. J. Giamarellos-Bourboulis has received honoraria from Abbott CH, bioMerieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi and XBiotech Inc; independent educational grants from Abbott CH, AxisShield, bioMerieux Inc, InflaRx GmbH, Johnson & Johnson, MSD, Sobi and XBiotech Inc.; and funding from the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grants ImmunoSep and RISKinCOVID (granted to the Hellenic Institute for the Study of Sepsis). G. Poulakou has received independent educational grants from Pfizer, MSD, Angelini, and Biorad. H. Milionis reports receiving honoraria, consulting fees and non-financial support from healthcare companies, including Amgen, Angelini, Bayer, Mylan, MSD, Pfizer, and Servier. L. Dagna had received consultation honoraria from SOBI. M. Bassetti has received funds for research grants and/or advisor/consultant and/or speaker/chairman from Angelini, Astellas, Bayer, Biomerieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Roche, Shionogi and Nabriva. P. Panagopoulos has received honoraria from GILEAD Sciences, Janssen, and MSD. G. N. Dalekos is an advisor or lecturer for Ipsen, Pfizer, Genkyotex, Novartis, Sobi, received research grants from Abbvie, Gilead and has served as PI in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc., Sobi and Intercept Pharmaceuticals. M. G. Netea is supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. Hes is a scientific founder of TTxD and he has received independent educational grants from TTxD, GSK, Ono Pharma and ViiV HealthCare. The other authors do not have any competing interest to declare. Ethics Approval Statement: The SAVE protocol was approved by the National Ethics Committee of Greece (approval 38/20) and National Organization for Medicines approval (ISO 28/20). The SAVE-MORE protocol was approved by the National Ethics Committee of Greece (approval 161/20) and by the Ethics Committee of the National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, in Rome (1 February 2021). Trial Registration: The SAVE study was prospectively registered prior to enrolling the first patient (EudraCT number 2020-001466-11; ClinicalTrials.gov identifier NCT04357366). The SAVE-MORE study was prospectively registered (EudraCT no. 2020-005828-11; ClinicalTrials.gov identifier NCT04680949). Written informed consent was provided by all patients prior to enrollment.

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

Right ventricular dysfunction is associated with high morbidity and mortality in candidates for left ventricular assist device (LVAD) implantation or cardiac transplantation.We examined the effects of prolonged intra-aortic balloon pump (IABP) support on right ventricular, renal and hepatic functions in patients presenting with end-stage heart failure.Between March 2008 and June 2013, fifteen patients (mean age = 49.5 years; 14 men) with end-stage systolic heart failure (HF), contraindications for any life saving procedure (conventional cardiac surgery, heart transplantation, LVAD implantation) and right ventricular dysfunction were supported with the IABP. The patients remained on IABP support for a mean of 73 ± 50 days (median 72, range of 13-155). We measured the echocardiographic and hemodynamic changes in right ventricular function, and the changes in serum creatinine and bilirubin concentrations before and during IABP support. Mean right atrial pressure decreased from 12.7 ± 6.5 to 3.8 ± 3.3 (P0.001) and pulmonary artery pressure decreased from 35.7 ± 10.6 to 25 ± 8.4 mmHg (P = 0.001), while cardiac index increased from 1.5 ± 0.4 to 2.2 ± 0.7 l/m(2)/min (P = 0.003) and right ventricular stroke work index from 485 ± 228 to 688 ± 237 mmHg × ml/m(2) (P = 0.043). Right ventricular end-diastolic diameter decreased from 34.0 ± 6.5 mm to 27.8 ± 6.2 mm (P0.001) and tricuspid annular systolic tissue Doppler velocity increased from 9.6 ± 2.4 cm/s to 11.1 ± 2.3 cm/s (P = 0.029). Serum creatinine and bilirubin decreased from 2.1 ± 1.3 to 1.4 ± 0.6 mg/dl and 2.0 ± 1.0 to 0.9 ± 0.5 mg/dl, respectively (P = 0.002 and P0.001, respectively).Prolonged IABP support of patients presenting with end-stage heart failure and right ventricular dysfunction induced significant improvement in right ventricular and peripheral organ function.

Loop diuretics are recommended for relieving symptoms and signs of congestion in patients with chronic heart failure and are administered to more than 80% of them. However, several of their effects have not systematically been studied. Numerous cohort and four interventional studies have addressed the effect of diuretics on renal function; apart from one prospective study, which showed that diuretics withdrawal is accompanied by increase in some markers of early-detected renal injury, all others converge to the conclusion that diuretics receipt, especially in high doses is associated with increased rates of renal dysfunction. Although a long standing perception has attributed a beneficial effect to diuretics in the setting of chronic heart failure, many cohort studies support that their use, especially in high doses is associated with adverse outcome. Several studies have used propensity scores in order to match diuretic and non-diuretic receiving patients; their results reinforce the notion that diuretics use and high diuretics dose are true risk factors and not disease severity markers, as some have suggested. One small, randomized study has demonstrated that diuretics decrease is feasible and safe and accompanied by a better prognosis. In conclusion, until elegantly designed, randomized trials, powered for clinical endpoints answer the unsettled issues in the field, the use of diuretics in chronic heart failure will remain subject to physicians' preferences and biases and not evidence based.

Objective Chronic intermittent renal replacement therapy(RRT) is an alternate method of decongestion for patients presenting with diuretic-resistant, end-stage heart failure(HF) and cardiorenal syndrome. The optimal method of vascular access has not been confirmed. This study investigated the 6-month outcomes of patients with end-stage HF after the creation of arteriovenous communications (AVC) compared with other means of RRT. Methods We treated 40 patients with chronic, intermittent, ambulatory RRT, of whom 15 (37.5%; Group A) underwent creation of AVC, and 25 (62.5%; Group B) received intraperitoneal (n = 6) or internal jugular catheters (n = 19) with the goal of achieving body weight stabilization and relief from congestion. Results The characteristics of the two groups were similar. According to Cox regression analysis, the 6-month rate of death or re-hospitalization for HF was significantly higher in Group A (73%) than in Group B (44%); hazard ratio (HR): 2.58; 95% confidence interval (CI) 1.2-6.2; P = 0.02. Over a 6-month follow-up, the cumulative survival was significantly shorter ( P = 0.03) in Group A (13.8 ± 10 weeks) than in Group B (20.7 ± 7 weeks). In the 15 patients who received AVC, the only independent predictor of adverse outcome at 6 months was serum total bilirubin concentration (HR 2.5; 95% CI 1.1-5.7, p = 0.02), whereas in the 25 patients who underwent other means of RRT, pulmonary vascular resistance (PVR) was identified as a risk factor for hospitalization or death at 1-year follow-up (HR 1.26; 95% CI 1.1-1.57, p = 0.04). Conclusion In patients with end-stage HF, the creation of AVC for intermittent RRT was followed by a significant increase in morbidity and mortality in comparison to the safe and effective placement of permanent central venous catheters. Patients with elevated PVR seem to comprise a group at high risk for adverse outcomes after central catheter insertion.

Background The intra-aortic balloon pump (IABP) can be used to bridge critically ill end-stage heart failure patients to left ventricular assist device (LVAD) implantation. However, the IABP's potential association with hemorrhagic complications raises concerns regarding its utilization in these patients. Aim We investigated whether preoperative long-term IABP support increases hemorrhagic complications post-LVAD implantation. Methods Ten patients undergoing IABP support prior to LVAD implantation (IABP-LVAD group) were compared with 16 who did not require IABP support (LVAD group). Results Mean duration of IABP support was 25.8 days. Preoperatively, both groups were comparable in all measured parameters and indices of end-organ function. Perioperative (defined as three weeks post-LVAD implantation, including the procedure) cellular and noncellular blood transfusion requirements were similar between IABP-LVAD and LVAD groups (19.8 ± 9.95 vs. 19.76 ± 29.69 RBC units, p = 0.96; 3.8 ± 4.14 vs. 2.0 ± 6.44 plateletpheresis units p = 0.84; 23 ± 16.04 vs. 25.14 ± 37.8 fresh frozen plasma units, p = 0.45). Perioperative minimum hematocrit (33.6 ± 5.6 vs. 36.59 ± 4.8, p = 0.38) and minimum platelet count (199 ± 153 vs. 144 ± 65, p = 0.52) were similar in the two groups. Two patients in the IABP-LVAD group and three patients in the LVAD group underwent reoperation post-LVAD implantation for bleeding. Length of ICU stay was longer in the LVAD group but did not reach statistical significance (6.2 ± 6.22 days in the IABP-LVAD group versus 13.45 ± 10.95 days in the LVAD group, p = 0.06). Conclusions Long-term IABP support as a bridge to LVAD implantation is not associated with increased hemorrhagic complications post-LVAD implantation. doi: 10.1111/jocs.12759 (J Card Surg 2016;31:467–471)

High doses of furosemide for heart failure (HF) have been correlated with an increased mortality, though whether they are a marker of disease severity or an independent predictor is unknown. We hypothesized that, in patients presenting with stable HF, the likelihood of long-term major adverse clinical events is increased by higher furosemide doses.We retrospectively recorded the doses of furosemide prescribed to 173 consecutive, clinically stable patients during a first ambulatory HF department visit. The low-dose group included 103 patients treated with 80 mg and the high-dose group included 70 patients treated with80 mg of furosemide daily. Proportional hazard regression analyses were performed with single and multiple variables in search of correlates of long-term adverse clinical events. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated.The baseline characteristics of the 2 groups were similar, except for estimated glomerular filtration rate, which was higher in the low- than the high-dose group (72.9 ± 19.4 vs. 60.8 ± 22.0 mL/min/ m2, p0.001). The 3-year survival free from the composite endpoint was significantly higher in the lowdose group than in the high-dose group (93.1% vs. 60.0%, p0.001). By multiple variable analysis, highdose furosemide was an independent predictor of an adverse outcome at 3 years (adjusted HR: 15.25; 95% CI:1.06-219.39, p=0.045). The incidence of deterioration of renal function and episodes of hypokalemia during follow up was also higher in the high furosemide dose (73.2% vs. 48.3, p=0.003, and 43.1% vs. 6.5%, p0.001, respectively).High doses of furosemide administered in order to stabilize HF patients and continued thereafter are associated with an adverse clinical outcome.

Administration of anticoagulation is mandatory in patients with left ventricular assist devices (LVADs). Vitamin K antagonists require regular monitoring and dosage adjustment. Dabigatran administered in a standard dose twice daily is more convenient and achieves a stable anticoagulant effect, but its effectiveness and safety in patients with LVADs has not been investigated. The objective of the present study was to evaluate whether dabigatran can be used safely as a second-line anticoagulation option in patients with a HeartMate II (HMII) LVAD.The study population consisted of 7 consecutive patients with end-stage heart failure who underwent HMII implantation and sequentially received acenocoumarol and dabigatran. Occurrence of stroke, systematic embolism, device thrombosis and major or life-threatening bleeding were included in the analysis. An acute decrease in plasma hemoglobin2 g/dL or a need for transfusion of at least 2 units of packed red blood cells (PRBC) was defined as major bleeding, while an acute decrease in plasma hemoglobin5 g/dL, fatal, symptomatic intracranial bleed, need for transfusion of at least 4 units PRBC, or association with hypotension requiring the use of intravenous inotropic agents or surgical intervention was defined as life-threatening bleeding.The duration of follow up was 1564 ± 292 days. Patients received acenocoumarol for 855 ± 246 days, followed by dabigatran for 708 ± 368 days. The rates of thromboembolic events were similar under dabigatran and acenocoumarol treatment: strokes, 0.094 vs. 0 /patient-year, p=0.36; systemic embolism, no event in either group; and device thrombosis, 0.053 vs. 0.258 events/patient-year, p=0.19, respectively. Compared to an adjusted acenocoumarol dose, the standard dabigatran dose resulted in similar rates of life-threatening bleeding, but significantly lower rates of major bleeding (0.18 vs. 0.27 bleeds/patient-years, p=0.76, and 0.047 vs. 0.547, p0.001, for dabigatran and acenocoumarol, respectively).The safe and effective use of dabigatran as a second-line anticoagulation therapy in patients with HMII seems feasible. However, these data must be confirmed in a randomized study.

Introduction: Heart failure (HF) treatment attracts a share of intensive research because of its poor HF prognosis. In the past decades, the prognosis of HF has improved considerably, mainly as a consequence of the progress that has been made in the pharmacological management of HF.Areas covered: This article reviews the outpatient pharmacological management of chronic HF due to left ventricular systolic dysfunction and offers recommendations on the use of various drugs. In addition, the present article attempts to provide practical therapeutic algorithms based on current clinical strategies.Expert opinion: Continued research directed toward identifying factors associated with high pharmacotherapy guideline adherence and understanding of variants that influence response to drugs will hopefully halt or reverse the major pathophysiological mechanisms involved in this syndrome.

Background Right heart failure (RHF) is a serious post-operative complication of left ventricular assist device (LVAD) implantation, with significant morbidity and mortality. Many clinical, hemodynamic and laboratory variables have been shown to have prognostic value for appearance of RHF. We sought to investigate the incidence of new-onset right ventricular dysfunction (RVD) complicating the long-term use of LVADs. Methods We retrospectively examined all patients supported with a continuous-flow LVAD for >1 year at our center. Results Twenty patients (mean age 54 ± 10 years, 95% men, 60% with ischemic cardiomyopathy, left ventricular ejection fraction 22 ± 6%, pulmonary capillary wedge pressure 23.5 ± 7.5 mm Hg, brain natriuretic peptide [BNP] 1,566 ± 1,536 pg/ml, serum creatinine 1.6 ± 0.64 mg/dl, furosemide dose 643 ± 410 mg/day) underwent long-term mechanical support as destination therapy support with a continuous-flow LVAD (HeartMate II) at our center. During follow-up (1,219 ± 692 days), 9 patients (45%) manifested symptoms and signs of RVD (increase in right atrial pressure [RAP], BNP and daily furosemide dose compared with the early post-operative period). In these patients, RAP was increased by 6.6 ± 2.6 mm Hg and BNP by 526 ± 477 pg/ml, whereas furosemide dose increased by 145 ± 119 mg. The mean and median times of RVD onset were 2.3 ± 1.5 and 2.1 years, respectively, after LVAD implantation (range 0.4 to 4.8 years). Four of these patients (44.4%) demonstrated further deterioration of RV function and died 73 ± 106 days (median 25 days, range 9 to 231 days) after first manifestation of RVD. Comparisons of baseline variables regarding medical history and clinical status did not demonstrate significant differences between the patients with or without RVD, including parameters related to RV function at the time of implantation. Conclusions Late-onset RVD is a complication of LVAD support, which can manifest several months to years from device implantation. This complication has significant adverse implications with regard to patient outcome. Prognostic factors need to be identified to follow and treat high-risk patients more efficiently.

Although the clinical assessment of jugular venous pressure (JVP) provides accurate estimate of right atrial pressure (RAP), there is no reliable non-invasive method for assessing pulmonary capillary wedge pressure (PCWP). Our objective was to evaluate the sensitivity and specificity for detecting elevated left ventricular filling pressures using a model for PCWP estimation, based on the clinical assessment of RAP and association between RAP and PCWP, which is unique for each patient, identified in a recent right heart catheterization (RHC).The study included 377 patients (age, 54.3 ± 13 years) with heart failure with reduced ejection fraction (left ventricular ejection fraction of 30.5 ± 10.8%) who underwent 2 RHCs within 1 year. In Group A (189 randomly selected patients), hemodynamic variables with significant correlation with the current wedge pressure (PCWP(2)) were identified and an equation estimating PCWP(2) based on these variables was formed. The validity of the equation was evaluated in the remaining 188 patients (Group B). The equation was also evaluated, prospectively in 39 new patients where RAP was estimated clinically, by physicians blinded to the results of the RHC.PCWP(2) in Group A correlated with RAP(1), systolic pulmonary artery pressure (SPAP(1)), and PCWP(1) of the first RHC and with RAP(2) and SPAP(2) of the second. The equation is PCWP(2) = [3RAP(2) + (PCWP(1) - RAP(1)) + 4]/2. In Group B, the sensitivity and specificity of estimated PCWP(2) for diagnosis of elevated LV filling pressures (invasive values18 mm Hg) was significant, reflected by an area under the curve (AUC) of 0.954 (p0.001). In the prospective sub-group, where JVP was entered in the formula as an estimate of RAP(2), correlation between estimated and measured PCWP(2) was r = 0.803 (p0.001).The current PCWP of a patient with heart failure can be estimated accurately by a simple equation based on measurements of a previous RHC and the current value of clinically assessed JVP.

Background Concern has been raised regarding the mortality and ethics related to the treatment of patients with end-stage chronic heart failure with chronic intermittent intravenous inotropic agents. We examined whether intermittent inotropic agents combined with oral amiodarone to prevent the proarrhythmic effect of inotropic agents results in better outcomes. Methods The study included 162 patients with decompensated end-stage chronic heart failure, who could be weaned from an initial 72-hour infusion of intravenous inotropes. Group 1 included 140 patients, who entered a 6-month program of weekly intermittent intravenous inotropic agents plus oral amiodarone, 200 mg twice a day. Group 2 included 22 patients, who were treated with optimal conventional therapy and were hospitalized for administration of intravenous medications as needed. Results The baseline characteristics of groups 1 versus 2, including New York Heart Association functional class (IV in both groups), admission systolic arterial blood pressure (99 +/- 14 vs. 97 +/- 13 mm Hg), right atrial pressure (13 +/- 6 vs. 14 +/- 6 mm Hg), pulmonary capillary wedge pressure (28 +/- 7 vs. 31 +/- 10 mm Hg), serum sodium (136 +/- 7 vs. 139 +/- 6 mEq/L) and serum creatinine (1.7 +/- 0.8 vs. 1.8 +/- 1.8 mg/dL), were similar. The 6-month (51% vs. 18%) and 1-year (36% vs. 9%) survival rates were significantly higher (P = 0.001 for both) in group 1 than in group 2. In addition, patients treated with intermittent intravenous inotropic agents improved their functional and hemodynamic status. Conclusions Intermittent intravenous inotropic agents combined with prophylactic oral amiodarone seem to improve the outcomes of patients with end-stage chronic heart failure. Further research is warranted to elucidate whether this treatment strategy should be considered as a standard therapy in patients with refractory end-stage heart failure.

To the Editor: The prevalence of anemia in patients with New York Heart Association (NYHA) functional class IV heart failure (HF) approaches 80% ([1][1]). Iron deficiency (ID) has been reported as the cause of anemia in more than 70% of advanced HF patients ([2][2]). The underlying mechanisms of ID

High doses of diuretics have been associated with increased mortality in chronic heart failure (HF). It remains unclear whether the administered dose represents a marker of clinical severity or if diuretics exert a deleterious effect. No evidence -based recommendations regarding their optimal use