Association Between Hemoglobin Levels and Efficacy of Intravenous Ferric Carboxymaltose in Patients With Acute Heart Failure and Iron Deficiency: An AFFIRM-AHF Subgroup Analysis.

BACKGROUND: Iron deficiency, with or without anemia, is an adverse prognostic factor in heart failure (HF). In AFFIRM-AHF (a randomized, double-blind placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalizations and mortality in iron-deficient subjects admitted for acute heart failure), intravenous ferric carboxymaltose (FCM), although having no significant effect on the primary end point, reduced the risk of HF hospitalization (hHF) and improved quality of life versus placebo in iron-deficient patients stabilized after an acute HF (AHF) episode. These prespecified AFFIRM-AHF subanalyses explored the association between hemoglobin levels and FCM treatment effects. METHODS: AFFIRM-AHF was a multicenter, double-blind, randomized, placebo-controlled trial of FCM in hospitalized AHF patients with iron deficiency. Patients were stratified by baseline hemoglobin level (<12 versus ≥12 g/dL). In each subgroup, the primary composite (total hHF and cardiovascular death) and secondary (total hHF; total cardiovascular hospitalizations and cardiovascular death; time to cardiovascular death, and time to first/days lost due to hHF or cardiovascular death) outcomes were assessed with FCM versus placebo at week 52. Sensitivity analyses using the World Health Organization anemia definition (hemoglobin level <12 g/dL [women] or <13 g/dL [men]) were performed, among others. RESULTS: Of 1108 AFFIRM-AHF patients, 1107 were included in these subanalyses: 464 (FCM group, 228; placebo group, 236) had a hemoglobin level <12 g/dL, and 643 (FCM, 329; placebo, 314) had a hemoglobin level ≥12 g/dL. Patients with a hemoglobin level <12 g/dL were older (mean, 73.7 versus 69.1 years), with more frequent previous HF (75.0% versus 68.7%), serum ferritin <100 µg/L (75.4% versus 68.1%), and transferrin saturation <20% (87.9% versus 81.4%). For the primary outcome, annualized event rates per 100 patient-years with FCM versus placebo were 71.1 and 73.6 (rate ratio, 0.97 [95% CI, 0.66-1.41]), respectively, and 48.5 versus 72.9 (RR, 0.67 [95% CI, 0.48-0.93]) in the hemoglobin levels <12 and ≥12 g/dL subgroups, respectively. No significant interactions between hemoglobin subgroup and treatment effect were observed for primary (Pinteraction=0.15) or secondary outcomes. Changes from baseline in hemoglobin, serum ferritin and transferrin saturation were significantly greater with FCM versus placebo in both subgroups between weeks 6 and 52. Findings were similar using the World Health Organization definition for anemia. CONCLUSIONS: The effects of intravenous FCM on outcomes in iron-deficient patients stabilized after an AHF episode, including improvements in iron parameters over time, did not differ between patients with hemoglobin levels <12 and ≥12 g/dL. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02937454.

Efficacy of ferric carboxymaltose in heart failure with iron deficiency: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Whereas a beneficial effect of intravenous ferric carboxymaltose (FCM) on symptoms and exercise capacity among patients with iron deficiency and heart failure (HF) has been consistently demonstrated, the effects of treatment on clinical events remain the subject of research. This meta-analysis aimed to characterize the effects of FCM therapy on hospitalizations and mortality. METHODS: Patient-level data from randomized, placebo-controlled FCM trials including adults with HF and iron deficiency with ≥52 weeks follow-up were analysed. The co-primary efficacy endpoints were (i) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death and (ii) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. Key secondary endpoints included individual composite endpoint components. Event rates were analysed using a negative binomial model. Treatment-emergent adverse events were also examined. RESULTS: Three FCM trials with a total of 4501 patients were included. Ferric carboxymaltose was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio 0.86; 95% confidence interval 0.75-0.98; P = .029; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (rate ratio 0.87; 95% confidence interval 0.75-1.01; P = .076; Cochran Q: 0.024). Treatment effects appeared to result from reduced hospitalization rates, not improved survival. Treatment appeared to have a good safety profile and was well tolerated. CONCLUSIONS: In iron-deficient patients with HF with reduced left ventricular ejection fraction, intravenous FCM was associated with significantly reduced risk of hospital admissions for HF and cardiovascular causes, with no apparent effect on mortality.

Practical Patient Care Considerations With Use of Vericiguat After Worsening Heart Failure Events.

Vericiguat is a soluble guanylate cyclase stimulator approved by multiple global regulatory bodies and recommended in recently updated clinical practice guidelines to reduce morbidity and mortality in patients with worsening chronic heart failure (HF) with reduced ejection fraction (HFrEF). Despite the growing armaments of evidence-based medical therapy for HFrEF that have demonstrated clinical outcome benefits, there is a need to address residual risk following worsening HF events. When considering therapies aimed to mitigate postevent cardiovascular risk, potential barriers preventing the prescription of vericiguat in eligible patients may include providers' lack of familiarity with it, clinical inertia, limited knowledge about monitoring response to therapy, and concerns about potential adverse effects as well as integration of its routine use during an era of in-person and telehealth hybrid ambulatory care. This review provides an overview of vericiguat therapy and proposes an evidence-based and practical guidance strategy toward implementing its use in various clinical settings. This review additionally summarizes patient counseling points for its initiation and maintenance.

Minimal Clinically Important Differences in 6-Minute Walk Test in Patients With HFrEF and Iron Deficiency.

BACKGROUND: The 6-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: To calculate the minimal clinically important difference (MCID) for change in exercise capacity in the 6MWT in iron-deficient populations with HFrEF. METHODS: In this pooled secondary analysis of the FAIR-HF and CONFIRM-HF trials, mean changes in the 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool (clinical anchor) to derive MCIDs in improvement and deterioration. RESULTS: Of 760 patients included in the 2 trials, 6MWT and PGA data were available for 680 (89%) and 656 (86%) patients at weeks 12 and 24, respectively. The mean 6MWT distance at baseline was 281 ± 103 meters. There was a modest correlation between changes in 6MWT and PGA from baseline to week 12 (r = 0.31; P < 0.0001) and week 24 (r = 0.43; P < 0.0001). Respective estimates (95% confidence intervals) of MCID in 6MWT at weeks 12 and 24 were 14 meters (5;23) and 15 meters (3;27) for a "little improvement" (vs no change), 20 meters (10;30) and 24 meters (12;36) for moderate improvement vs a "little improvement,", -11 meters (-32;9.2) and -31 meters (-53;-8) for a "little deterioration" (vs no change), and -84 meters (-144;-24) and -69 meters (-118;-20) for "moderate deterioration" vs a "little deterioration". CONCLUSIONS: The MCID for improvement in exercise capacity in the 6MWT was 14 meters-15 meters in patients with HFrEF and iron deficiency. These MCIDs can aid clinical interpretation of study data.

Intravenous ferric carboxymaltose for iron repletion following acute heart failure in patients with and without diabetes: a subgroup analysis of the randomized AFFIRM-AHF trial.

BACKGROUND: In AFFIRM-AHF, treatment of iron deficiency with intravenous ferric carboxymaltose (FCM) reduced the risk of heart failure (HF) hospitalization and improved quality of life (QoL) vs placebo in patients stabilized following an acute HF (AHF) episode, with no effect on cardiovascular (CV) death. Diabetes and iron deficiency frequently accompany AHF. This post hoc analysis explored the effects of diabetes on outcomes in AFFIRM-AHF patients. METHODS: Patients were stratified by diabetes yes/no at baseline. The effects of FCM vs placebo on primary (total HF hospitalizations and CV death) and secondary (total CV hospitalizations and CV death; CV death; total HF hospitalizations; time to first HF hospitalization or CV death; and days lost due to HF hospitalizations or CV death) endpoints at Week 52 and change vs baseline in disease-specific QoL (12-item Kansas City Cardiomyopathy Questionnaire [KCCQ-12]) at Week 24 were assessed by subgroup. For each endpoint, the interaction between diabetes status and treatment outcome was explored. RESULTS: Of 1108 AFFIRM-AHF patients, 475 (FCM: 231; placebo: 244) had diabetes and 633 (FCM: 327; placebo: 306) did not have diabetes. Patients with diabetes were more commonly male (61.5% vs 50.9%), with a higher frequency of ischemic HF etiology (57.9% vs 39.0%), prior HF history (77.7% vs 66.5%), and comorbidities (including previous myocardial infarction [49.3% vs 32.9%] and chronic kidney disease [51.4% vs 32.4%]) than those without diabetes. The annualized event rate/100 patient-years with FCM vs placebo for the primary endpoint was 66.9 vs 80.9 in patients with diabetes (rate ratio [RR]: 0.83, 95% CI 0.58-1.81) and 51.3 vs 66.9 in patients without diabetes (RR: 0.77, 95% CI 0.55-1.07), with no significant interaction between diabetes status and treatment effect (pinteraction = 0.76). Similar findings were observed for secondary outcomes. Change from baseline in KCCQ-12 overall summary score was numerically greater with FCM vs placebo at almost all time points in both subgroups, with no interaction between diabetes and treatment effect at Week 24. CONCLUSIONS: The clinical and QoL benefits observed with intravenous FCM in patients with iron deficiency following stabilization from an AHF episode are independent of diabetes status. Trial registration Clinicaltrials.gov, NCT02937454 (registered 10.18.2016).

The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study.

AIMS: Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. METHODS AND RESULTS: The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5-5.3, P = 0.018) for OSS and 2.8 (0.3-5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3-5.6, P = 0.028) for OSS and 2.9 (0.2-5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. CONCLUSION: In iron-deficient patients with HF and left ventricular ejection fraction <50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial.

BACKGROUND: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. METHODS: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. FINDINGS: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group. INTERPRETATION: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING: Vifor Pharma.

Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure.

In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as follows. At-risk for HF (Stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). The classification includes HF with reduced EF (HFrEF): HF with an LVEF of ≤40%; HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%; HF with preserved EF (HFpEF): HF with an LVEF of ≥50%; and HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a ≥10-point increase from baseline LVEF, and a second measurement of LVEF of >40%.

Expression of sex steroid receptors and aromatase in adipose tissue in different body regions in men with coronary artery disease with and without ischemic systolic heart failure.

Background: The hormonal metabolism of adipose tissue differs across regions of fat. This issue has never been verified in male patients with coronary artery disease (CAD) with and without systolic heart failure (SHF).Methods: We examined 90 male patients with CAD with and without SHF and 42 healthy controls.Results: In patients with CAD with and without SHF, androgen receptor (AR) expression in adipose tissue of the lower leg was higher than AR expression of the thoracic wall and epicardial adipose tissue (EAT) (both p < .0001 for SHF patients and both p < .001 for patients without SHF). Expression of aromatase in adipose tissue of the lower leg among patients with CAD and SHF was higher than aromatase expression of the thoracic wall and EAT (p < .001 and p < .05, respectively), and in patients without SHF, it was higher only than aromatase expression of the thoracic wall (p < .05). There were no differences in expression of estrogen receptor (ER) between three regions of adipose tissue both in men with CAD with and without SHF.Conclusions: In male patients with CAD, site-related differences of adipose tissue in expression of AR and aromatase are present regardless of coexisting SHF with the highest hormonal activity within peripheral subcutaneous adipose tissue.

Deranged Iron Status Evidenced by Iron Deficiency Characterizes Patients with Hidradenitis Suppurativa.

BACKGROUND: Proinflammatory activation and autoimmune processes underlie the pathophysiology of hidradenitis suppurativa (HS). Iron deficiency (ID) is frequently present in inflammation-mediated chronic diseases, irrespective of anemia. OBJECTIVES: We aimed to characterize iron status in patients with HS. METHODS: Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor and hepcidin were assessed as the biomarkers of iron status in 74 patients with HS and 44 healthy subjects. ID was defined as ferritin <100 µg/L or ferritin 100-299 µg/L with Tsat <20% (following the definition used in the other studies in chronic disease). RESULTS: Compared with controls, patients with HS demonstrated a deranged iron status as evidenced by decreased levels of ferritin (91 ± 87 vs. 157 ± 99 µg/L), Tsat (21.5 ± 10.8 vs. 42.2 ± 11.7%) and hepcidin (31.3 ± 25.9 vs. 44.2 ± 22.0 ng/mL) (all p < 0.05 vs. controls). There was also a trend toward higher values of soluble transferrin receptor (1.23 ± 0.35 vs. 1.12 ± 0.19 mg/L) (p = 0.09 vs. controls). Disease severity (assessed with the Hidradenitis Suppurativa Severity Index and the 3-degree Hurley scale) did not differentiate iron status biomarkers. ID was present in 75% of HS patients, and its prevalence was not related with disease severity (Hurley I/II/III - 82 vs. 73 vs. 67%). In HS, none of the iron status biomarkers correlated with the levels of interleukin-6 (a marker of proinflammatory activation). CONCLUSIONS: The majority of HS patients demonstrate derangements in iron status typical of ID. These abnormalities are neither related to proinflammatory activation nor associated with disease severity. Whether it may have a therapeutic impact needs to be further studied.

Structural and functional abnormalities in iron-depleted heart.

Iron deficiency (ID) is a common and ominous comorbidity in heart failure (HF) and predicts worse outcomes, independently of the presence of anaemia. Accumulated data from animal models of systemic ID suggest that ID is associated with several functional and structural abnormalities of the heart. However, the exact role of myocardial iron deficiency irrespective of systemic ID and/or anaemia has been elusive. Recently, several transgenic models of cardiac-specific ID have been developed to investigate the influence of ID on cardiac tissue. In this review, we discuss structural and functional cardiac consequences of ID in these models and summarize data from clinical studies. Moreover, the beneficial effects of intravenous iron supplementation are specified.

Monitoring of iron status in patients with heart failure.

The 2016 ESC/HFA heart failure (HF) guidelines emphasize the importance of identifying and treating iron deficiency (ID) in patients with HF. Iron deficiency can occur in half or more of HF sufferers, depending on age and the phase of the disease. Iron deficiency can be a cause of anaemia, but it is also common even without anaemia, meaning that ID is a separate entity, which should be screened for within the HF population. Although assessment of iron stores in bone marrow samples is the most accurate method to investigate iron status, it is not practical in most HF patients. Levels of circulating iron biomarkers are an easily available alternative; especially, ferritin and transferrin saturation (Tsat). In patients with HF serum ferritin level <100 µg/L (regardless of Tsat value) or between 100 and 299 µg/L with Tsat <20% are considered as recommended criteria for the diagnosis of ID, criteria which have been used in the clinical trials in HF that have led to a recommendation to treat ID with intravenous iron. We discuss the optimal measures of iron biomarkers in patients with HF in order to screen and monitor iron status and introduce some novel ways to assess iron status.

Drug therapy in elderly heart failure patients.

Although heart failure (HF) is considered as a cardiogeriatric syndrome, elderly and very elderly patients are under-represented in the vast majority of clinical trials investigating novel drugs and therapies in this population. The homoeostatic systems of elderly subjects are very fragile, and the management of HF accompanied by numerous comorbidities requires a holistic approach towards the patient, with special emphasis not only on psychosomatic problems but also on the individual (including social) needs of each particular patient, along with the support for the family and/or caregivers. In this article, we summarize current evidence regarding pharmacotherapy of elderly patients with HF and summarize the clinical problems occurring in this population.

Central Chemoreceptor Sensitivity Is Not Enhanced in Contemporary Patients With Chronic Systolic Heart Failure Receiving Optimal Treatment.

BACKGROUND: Clinical and prognostic consequences of enhanced central chemosensitivity in the contemporary optimally treated patients with chronic heart failure (CHF) are unknown. METHODS AND RESULTS: We studied central chemosensitivity (defined as hypercapnic ventilatory response [HCVR; L/min/mmHg]) in 161 CHF patients (mean left ventricular ejection fraction [LVEF] 31 ± 6%, all receiving a combination of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker) and 55 sex- and age-matched healthy controls. HCVR did not differ between CHF patients and controls (median 0.63 vs 0.57 L/min-1/mmHg-1, P = .76). When the CHF patients were divided into tertiles according to their HCVR values, there were no significant differences in clinical characteristics (except for ischemic etiology, which was more frequent in those with the highest HCVR), results of the cardiopulmonary exercise testing, and indices of heart rate variability. During the follow-up (median 28 months, range 1-48 months, ≥15 months in all survivors), 21 patients died. HCVR was not related to survival in the Cox proportional hazards analysis. CONCLUSIONS: Central chemosensitivity is not enhanced in contemporary, optimally treated CHF patients and its assessment does not provide significant clinical or prognostic information.

Iron Deficiency Treatment in Patients with Heart Failure.

Iron deficiency (ID) is one of the major risk factors for disability and mortality worldwide, and it was identified as a common and ominous comorbidity in patients with heart failure (HF), both with and without anaemia. Based on two clinical trials (FAIR-HF and CONFIRM-HF) and other epidemiological evidence, ID has been recognized as an important therapeutic target in symptomatic patients with HF and LVEF ≤45%.Intravenous iron supplementation has been demonstrated to be safe and effective for iron repletion and related with an improvement in clinical status, exercise capacity, and quality of life. Ongoing trials are testing the hypothesis that such a therapy may also reduce the risk of HF hospitalizations and cardiovascular death.