Background Intravenous ferric carboxymaltose (FCM) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not ...fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty-three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double-blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least-square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65-78) years, with N-terminal pro-B-type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010-2828), 63 ng/mL (22-114), and 15.7% (11.0-19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 34.6-38.7 versus 40 38-42.1,
=0.025; 1061 1051-1072 versus 1085 1074-1095,
=0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 34.1-38.5 versus 41.1 38.9-43.4,
=0.003), but not for T1 mapping (1075 1065-1085 versus 1079 1069-1089,
=0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03398681.
We aimed to assess the association between CA125 and the long-term risk of total acute heart failure (AHF) admissions in patients with an index hospitalization with AHF and preserved ejection ...fraction (HFpEF). We prospectively included 2369 patients between 2008 and 2019 in three centers. CA125 and NT-proBNP were measured during early hospitalization and evaluated as continuous and categorized in quartiles (Q). Negative binomial regressions were used to assess the association with the risk of recurrent AHF admission. The mean age of the sample patients was 76.7 ± 9.5 years and 1443 (60.9%) were women. Median values of CA125 and NT-proBNP were 38.3 (19.0-90.0) U/mL, and 2924 (1590-5447) pg/mL, respectively. During a median follow-up of 2.2 (0.8-4.6) years, 1200 (50.6%) patients died, and 2084 AHF admissions occurred in 1029 (43.4%) patients. After a multivariate adjustment, CA125, but not NT-proBNP, was positively and non-linearly associated with the risk of cumulative AHF-readmission (p < 0.001). Compared to Q1, patients belonging to Q2, Q3, and Q4 showed a stepwise risk increase (IRR = 1.29, 95% CI 1.08-1.55, p = 0.006; IRR = 1.35, 95% CI 1.12-1.63, p = 0.002; and IRR = 1.62, 95% CI 01.34-1.96, p < 0.001, respectively). In conclusion, CA125 predicted the risk of long-term AHF-readmission burden in patients with HFpEF and a recent admission for AHF.
Background
Iron deficiency (ID) is associated with impaired functional capacity in patients with heart failure (HF), even in those with preserved ejection fraction (HFpEF). This study aimed to ...evaluate the effect of baseline ferrokinetics on peak oxygen consumption (peakVO2) improvement after a 12‐week physical therapy programme in patients with stable HFpEF.
Methods
This study is a post‐hoc sub‐analysis of a randomized clinical trial in which 59 stable patients with HFpEF were randomized to receive a 12‐week programme of inspiratory muscle training (IMT), functional electrical stimulation (FES), IMT + FES or usual care (UC) to evaluate change in peakVO2 (NCT02638961). Serum ferritin and transferrin saturation (TSAT) determinations were assessed at baseline. ID was defined as ferritin <100 ng/mL and/or TSAT <20% if ferritin was within 100–299 ng/mL. We used a linear mixed regression model to analyse between‐treatment changes in peakVO2 across ferrokinetics status at 12 and 24 weeks.
Results
The mean age was 74 ± 9 years, and 36 (61%) had ID. The mean of peakVO2 was 9.9 ± 2.5 mL/kg/min. The median of ferritin and transferrin saturation (TSAT) was 91 (50–181) ng/mL and 23% (16–30), respectively. A total of 52 patients completed the trial (13 patients per arm). Compared with those patients on UC, patients allocated to any of the active arms showed less improvement in peak VO2 when they showed ID (P‐value for interaction <0.001), lower values of ferritin (P‐value for interaction <0.001), or TSAT (P‐value for interaction <0.001).
Conclusions
Ferrokinetics status plays an essential role in modifying the aerobic capacity response to physical therapies in patients with HFpEF. Further studies are required to confirm these findings.
BackgroundFatigue and exercise intolerance are the most common symptoms in patients with long COVID.AimsThis study aimed to evaluate whether a home-based inspiratory muscle training (IMT) programme ...improves maximal functional capacity in patients’ long COVID after a previous admission due to SARS-CoV-2 pneumonia.MethodsThis study was a single-centre, blinded assessor, randomised controlled trial. Twenty-six patients with long COVID and a previous admission due to SARS-CoV-2 pneumonia were randomly assigned to receive either a 12-week IMT or usual care alone (NCT05279430). The physiotherapist and participants were not blinded. Patients allocated to the IMT arm were instructed to train at home twice daily using a threshold inspiratory muscle trainer and to maintain diaphragmatic breathing during the training session. The usual care arm received no intervention.The primary endpoint was the change in peak oxygen consumption (peakVO2). Secondary endpoints were changes in quality of life (QoL), ventilatory efficiency and chronotropic response during exercise (evaluated by chronotropic index-CIx- formula). We used linear mixed regression analysis for evaluating changes in primary and secondary endpoints.ResultsThe mean age of the sample and time to first visit after discharge were 50.4±12.2 years and 362±105 days, respectively. A total of 11 (42.3%) were female. At baseline, the mean of peakVO2, ventilatory efficiency and CIx were 18.9±5 mL/kg/min, 29.4±5.2 and 0.64±0.19, respectively. The IMT arm improved their peakVO2 significantly compared with usual care (+Δ 4.46 mL/kg/min, 95% CI 3.10 to 5.81; p<0.001). Similar positive findings were found when evaluating changes for CIx and some QoL dimensions. We did not find significant changes in ventilatory efficiency.ConclusionIn long COVID patients with a previous admission due to SARS-CoV-2 pneumonia, IMT was associated with marked improvement in exercise capacity and QoL.Trial registration numberNCT05279430.
Background Following a heart failure (HF)-decompensation, there is scarce data about sex-related prognostic differences across left ventricular ejection fraction (LVEF) status. We sought to evaluate ...sex-related differences in 6-month mortality risk across LVEF following admission for acute HF. Methods and Results We retrospectively evaluated 4812 patients consecutively admitted for acute HF in a multicenter registry from 3 hospitals. Study end points were all-cause, cardiovascular, and HF-related mortality at 6-month follow-up. Multivariable Cox regression models were fitted to investigate sex-related differences across LVEF. A total of 2243 (46.6%) patients were women, 2569 (53.4%) were men, and 2608 (54.2%) showed LVEF≥50%. At 6-month follow-up, 645 patients died (13.4%), being 544 (11.3%) and 416 (8.6%) cardiovascular and HF-related deaths, respectively. LVEF was not independently associated with mortality (HR, 1.02; 95% CI 0.99-1.05;
=0.135). After multivariable adjustment, we found no sex-related differences in all-cause mortality (
value for interaction=0.168). However, a significant interaction between sex and cardiovascular and HF mortality risks was found across LVEF (
value for interaction=0.030 and 0.007, respectively). Compared with men, women had a significantly lower risk of cardiovascular and HF-mortality at LVEF<25% and <43%, respectively. On the contrary, women showed a higher risk of HF-mortality at the upper extreme of LVEF (>80%). Conclusions Following an admission for acute HF, no sex-related differences were found in all-cause mortality risk. However, when compared with men, women showed a lower risk of cardiovascular and HF-mortality at the lower extreme of LVEF. On the contrary, they showed a higher risk of HF death at the upper extreme.
Women represent nearly half of the adult heart failure (HF) population and they remain underrepresented in HF studies. We aimed to evaluate the evidence about peak oxygen uptake (peak VO2) for ...clinical stratification in women with HF. This narrative review summarizes (i) the evidence endorsing the value of cardiopulmonary exercise testing for clinical stratification and phenotyping HF population; (ii) the determinants of a person's functional aerobic capacity to understand predicted values for patients with chronic HF; and (iii) sex differences on peak VO2 data in different forms of HF. Lastly, based on existing data in patients with HF, we provide a perspective on how to improve existing gaps about the utility of peak VO2 in clinical stratification in women. Peak VO2 provides prognosis information in patients with HF; however, its use has been limited for a reduced number of patients excluding women, elderly, and HF patients with preserved ejection fraction. Further studies will help to fill the wide gender gap about the utility of cardiopulmonary exercise testing in the risk assessment and management in women with HF.
Background The mechanisms explaining the clinical benefits of ferric carboximaltose (FCM) in patients with heart failure, reduced or intermediate left ventricular ejection fraction, and iron ...deficiency remain not fully clarified. The Myocardial-IRON trial showed short-term cardiac magnetic resonance (CMR) changes suggesting myocardial iron repletion following administration of FCM but failed to find a significant increase in left ventricular ejection fraction in the whole sample. Conversely, the strain assessment could evaluate more specifically subtle changes in contractility. In this subanalysis, we aimed to evaluate the effect of FCM on the short-term left and right ventricular CMR feature tracking derived strain. Methods and Results This is a post hoc subanalysis of the double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with heart failure and left ventricular ejection fraction <50%, and iron deficiency Myocardial-IRON trial (NCT03398681). Three-dimensional left and 2-dimensional right ventricular CMR tracking strain (longitudinal, circumferential, and radial) changes were evaluated before, 7 and 30 days after randomization using linear mixed-effect analysis. The median (interquartile range) age of the sample was 73 years (65-78), and 40 (75.5%) were men. At baseline, there were no significant differences in CMR feature tracking strain parameters across both treatment arms. At 7 days, the only global 3-dimensional left ventricular circumferential strain was significantly higher in the FCM treatment-arm (difference: -1.6%,
=0.001). At 30 days, and compared with placebo, global 3-dimensional left ventricular strain parameters significantly improved in those allocated to FCM treatment-arm longitudinal (difference: -2.3%,
<0.001), circumferential (difference: -2.5%,
<0.001), and radial (difference: 4.2%,
=0.002). Likewise, significant improvements in global right ventricular strain parameters were found in the active arm at 30 days (longitudinal difference: -3.3%,
=0.010, circumferential difference: -4.5%,
<0.001, and radial difference: 4.5%,
=0.027). Conclusions In patients with stable heart failure, left ventricular ejection fraction <50%, and iron deficiency, treatment with FCM was associated with short-term improvements in left and right ventricular function assessed by CMR feature tracking derived strain parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03398681.
IntroductionExercise intolerance and fatigue are the most common symptoms in patients with chronic COVID-19 after hospital discharge. Supervised exercise training programmes improve symptoms, but ...scarce research has been done on home-based exercise programmes on the maximal functional capacity for discharged symptomatic COVID-19 patients. This study evaluates whether a home-based inspiratory muscle training (IMT) programme improves maximal functional capacity in chronic COVID-19 after hospital admission.Methods and analysisThis single-centre, assessor-blinded randomised controlled trial, powered for superiority, seeks to evaluate maximal functional capacity as the primary endpoint. A total of 26 eligible patients with a previous admission for acute respiratory syndrome coronavirus 2 pneumonia (>3 months after hospital discharge) will be randomised (1:1) to receive a 12-week programme of IMT versus usual care alone. A blinded assessor will measure outcomes at baseline and after the intervention (12 weeks). An analysis of variance will be used to compare continuous outcomes among the two-intervention groups. As of 21 March 2022, eight patients have been enrolled.Ethics and disseminationThe research ethics committee (Comité Ético de Investigación con Medicamentos de l'Hospital Clínic Universitari de València) approved the protocol following the principles of the Declaration of Helsinki and national regulations (Approval Number: 021/226). Findings will be published in peer-reviewed journals and conference publications.Trial registration numberNCT05279430.
Galectin-3 (Gal-3) and carbohydrate antigen 125 (CA125) have emerged as robust prognostic biomarkers in heart failure. Experimental data have also suggested a potential molecular interaction between ...CA125 and Gal-3; however, the biological and clinical relevance of this interaction is still uncertain. We sought to evaluate, in patients admitted for acute heart failure, the association between plasma Gal-3 with all-cause mortality and the risk for rehospitalizations among high and low levels of CA125.
We included 264 consecutive patients admitted for acute heart failure to the Cardiology Department in a third-level center. Both biomarkers were measured on admission. Negative binomial and Cox regression models were used to evaluate the prognostic effect of the interaction between Gal-3 and CA125 (dichotomized by its median) with hospital readmission and all-cause mortality, respectively. During a median follow-up of 2 years (IQR = 1-2.8), 108 (40.9%) patients deaths and 365 rehospitalizations in 171 (69.5%) patients were registered. In a multivariable setting, the effect of Gal-3 on mortality and rehospitalization was differentially mediated by CA125 (p = 0.007 and p<0.001, respectively). Indeed, in patients with CA125 above median (>67 U/ml), values across the continuum of Gal-3 showed a positive and almost linear relationship with either the risk of death or rehospitalization. Conversely, when CA125 was below median (≤67 U/ml), Gal-3 lacked any prognostic effect on both endpoints.
In patients with acute heart failure, Gal-3 was strongly associated with higher risk of long-term mortality and repeated rehospitalizations, but only in those patients exhibiting higher values of CA125 (above 67 U/ml).
Aims
The mechanisms underlying the beneficial effect of ferric carboxymaltose (FCM) in patients with heart failure (HF) and iron deficiency (ID) have not been completely characterized. The ...Myocardial‐IRON trial was a double‐blind, randomized trial that evaluated myocardial iron repletion following FCM vs. placebo in 53 patients with HF and ID. In this post hoc analysis, we evaluated whether treatment with FCM was associated with cardiac magnetic resonance changes in left and right ventricular function (LVEF and RVEF, respectively) at different points of systolic dysfunction.
Methods and results
We included patients from the Myocardial‐IRON trial with left and right ventricular systolic dysfunction (LVSD and RVSD, respectively) at enrolment. Linear mixed regression models were used to evaluate changes at 7 and 30 days on LVEF and RVEF at cardiac magnetic resonance. At enrolment, 27 (50.9%) and 38 (71.7%) patients had LVEF < 40% (LVSD1) or <45% (LVSD2), respectively, and 10 (18.9%) and 17 (32.1%) patients had RVEF < 45% (RVSD1) or <51% in women and <52% in men (RVSD2), respectively. Treatment with FCM was associated with a significant improvement in LVEF at 30 days (LVSD1: Δ2.3%, P < 0.001; LVSD2: Δ4.1, P = 0.014). FCM was also associated with a significant and early improvement in RVEF at 7 days (RVSD1: Δ6.9%, P = 0.003; RVSD2: Δ3.2%, P = 0.003) that persisted at 30 days (RVSD1: Δ8.1%, P < 0.001; RVSD2: Δ4.7%, P < 0.001).
Conclusions
In patients with HF and systolic dysfunction with ID, FCM was associated with short‐term improvement in LVEF and, especially, in RVEF.
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