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Introduction and Objectives: Little is known about the usefulness of heart rate (HR) response to exercise for risk stratification in heart failure with preserved ejection fraction (HFpEF). Therefore, this study aimed to assess the association between HR response to exercise and the risk of total episodes of worsening heart failure (WHF) in symptomatic stable patients with HFpEF., Methods: This single-center study included 133 patients with HFpEF (NYHA II-III) who performed maximal cardiopulmonary exercise testing. HR response to exercise was evaluated using the chronotropic index (CI x ) formula. A negative binomial regression method was used., Results: The mean age of the sample was 73.2± 10.5 years; 56.4% were female, and 51.1% were in atrial fibrillation. The median for CI x was 0.4 [0.3-0.55]. At a median follow-up of 2.4 [1.6-5.3] years, a total of 146 WHF events in 58 patients and 41 (30.8%) deaths were registered. In the whole sample, CI x was not associated with adverse outcomes (death, P=.319, and WHF events, P=.573). However, we found a differential effect across electrocardiographic rhythms for WHF events (P for interaction=.002). CI x was inversely and linearly associated with the risk of WHF events in patients with sinus rhythm and was positively and linearly associated with those with atrial fibrillation., Conclusions: In patients with HFpEF, CI x was differentially associated with the risk of total WHF events across rhythm status. Lower CI x emerged as a risk factor for predicting higher risk in patients with sinus rhythm. In contrast, higher CI x identified a higher risk in those with atrial fibrillation., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: The heterogeneity of patients with heart failure and preserved ejection fraction (HFpEF) is high, thusthis entity tends to be grouped into phenotypes to act with precision. Within these groups, patients with type 2 diabetes mellitus (T2DM) hold this heterogeneity. Our aim is to describe subgroups of patients with HFpEF and T2DM based on other comorbidities., Material and Methods: Patients were recruited from the national registry of heart failure (RCIA). Patients with ejection fraction greater than or equal to 50% without valvular disease and with T2DM were included. A hierarchical agglomerative analysis was performed with Ward's method including the following variables: dyslipidemia, liver disease, Chronic obstructive pulmonary disease (COPD), dementia, cerebrovascular disease, arrhythmia, systolic blood pressure, body mass index (BMI), estimation of glomerular filtration and hemoglobin., Results: 1934 patients with ICFEP were included, of which 907 (46.9%) had T2DM with a predominance of women (60.9%) and with a BMI of 31.1 (5.9) Kg / m2. Four groups were obtained, two with high vascular risk (one with arrhythmia and the other without it) with 263 patients the first and 201 the second. A third group had a predominance of COPD (140 patients) and a last group with 303 patients older but with less comorbidity., Conclusions: In our patients with ICFEP and T2DM, obesity and female sex predominated. All four groups offered treatment chances to improve their prognosis not only based on the use of new antidiabetic drugs but also on other options that may be a starting point for further research., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Introduction and Objectives: Type 2 diabetes mellitus (DM2) is a common comorbidity in patients with heart failure (HF) with preserved ejection fraction (HFpEF). Previous studies have shown that diabetic women are at higher risk of developing HF than men. However, the long-term prognosis of diabetic HFpEF patients by sex has not been extensively explored. In this study, we aimed to evaluate the differential impact of DM2 on all-cause mortality in men vs women with HFpEF after admission for acute HF., Methods: We prospectively included 1019 consecutive HFpEF patients discharged after admission for acute HF in a single tertiary referral hospital. Multivariate Cox regression analysis was used to evaluate the interaction between sex and DM2 regarding the risk of long-term all-cause mortality. Risk estimates were calculated as hazard ratios (HR)., Results: The mean age of the cohort was 75.6±9.5 years and 609 (59.8%) were women. The proportion of DM2 was similar between sexes (45.1% vs 49.1, P=.211). At a median (interquartile range) follow-up of 3.6 (1-4-6.8) years, 646 (63.4%) patients died. After adjustment for risk factors, comorbidities, biomarkers, echo parameters and treatment at discharge, multivariate analysis showed a differential prognostic effect of DM2 (P value for interaction=.007). DM2 was associated with a higher risk of all-cause mortality in women (HR, 1.77; 95%CI, 1.41-2.21; P <.001) but not in men (HR, 1.23; 95%CI, 0.94-1.61; P=.127)., Conclusions: After an episode of acute HF in HFpEF patients, DM2 confers a higher risk of mortality in women. Further studies evaluating the impact of DM2 in women with HFpEF are warranted., (Copyright © 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Lysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences., Methods: We quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls. We also assessed the correlations of cpLOX with myocardial stiffness parameters, collagen turnover products and fibrogenic cytokines, as well as the predictive value of plasma proenzyme levels at 1-year of follow-up., Results: We detected raised cpLOX values and found that they correlated with calculated E/E' ratios and stiffness constants. The subgroup of patients with type I diastolic dysfunction showed a single negative correlation between cpLOX and B-type natriuretic peptide whereas patients with a restrictive diastolic pattern showed a strong correlation between cpLOX and galectin-3. Kaplan-Meier analysis revealed that cpLOX > 52.20 ng/mL slightly increased the risk of a fatal outcome (log-rank = 4.45; P = .034). When Cox regression was used, cpLOX was found to be a significant independent predictor of cardiovascular death or hospitalization due to the decompensation of HM-HFpEF (HR, 1.360; 95%CI, 1.126-1.638; P = .046)., Conclusions: Patients with symptomatic HM-HFpEF show high cpLOX serum levels associated with restrictive diastolic filling indices. These levels represent a moderate risk factor for poor clinical outcome. Throughout the natural history of HM-HFpEF, we observed that cpLOX concentrations were initially negatively correlated with B-type natriuretic peptide but positively correlated with galectin-3 as advanced diastolic dysfunction developed., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Despite the prevalence of heart failure with preserved ejection fraction (HFpEF), there is currently no evidence-based effective therapy for this disease. This study sought to evaluate whether inspiratory muscle training (IMT), functional electrical stimulation (FES), or a combination of both (IMT + FES) improves 12- and 24-week exercise capacity as well as left ventricular diastolic function, biomarker profile, and quality of life in HFpEF., Methods: A total of 61 stable symptomatic patients (New York Heart Association II-III) with HFpEF were randomized (1:1:1:1) to receive a 12-week program of IMT, FES, or IMT + FES vs usual care. The primary endpoint of the study was to evaluate change in peak exercise oxygen uptake at 12 and 24 weeks. Secondary endpoints were changes in quality of life, echocardiogram parameters, and prognostic biomarkers. We used a mixed-effects model for repeated-measures to compare endpoints changes., Results: Mean age and peak exercise oxygen uptake were 74 ± 9 years and 9.9 ± 2.5mL/min/kg, respectively. The proportion of women was 58%. At 12 weeks, the mean increase in peak exercise oxygen uptake (mL/kg/min) compared with usual care was 2.98, 2.93, and 2.47 for IMT, FES, and IMT + FES, respectively (P < .001) and this beneficial effect persisted after 6 months (1.95, 2.08, and 1.56; P < .001). Significant increases in quality of life scores were found at 12 weeks (P < .001). No other changes were found., Conclusions: In HFpEF patients with low aerobic capacity, IMT and FES were associated with a significant improvement in exercise capacity and quality of life. This trial was registered at ClinicalTrials.gov (Identifier: NCT02638961).., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Heart failure (HF) with recovered ejection fraction (EF) is emerging as a different HF subtype. There is little information about his clinical profile in hospitals that are not a reference., Methods: We analysed characteristics and prognosis in patients with recovered HF followed prospectively in the HF Unit of a non-tertiary hospital., Results: A total of 431 patients with HF with reduced EF were followed (median 50 months, 79.3% males, mean age 70.3±12.2years). Of the patients, 26.9% (N 116) recovered EF, mainly in the first year of follow-up (76.7%). Compared with patients that did not recovered EF in the follow-up, they were younger, rate of ischemic origin of cardiomyopathy was less frequent and presented less comorbidity. Mortality was lower in patients with recovered HF (survival median of 85.2±2.1 vs. 74.2±1.9 months [log-rank χ 2 11.5, P=0.001], hazard ratio 0.37, 95% confidence interval [CI]: 0.21-0.67, P=0.002). Aetiology of deaths was not mainly secondary to HF. Younger age of 68 years (odds ratio [OR] 0-98, 95% CI: 0.96-0,99; P=0.025), ischemic origin (OR 1.12, 95% CI: 1.01-1.21; P=0.003) and use of aldosterone antagonists (OR 1.89, 95% CI: 1.09-3.26; P=0.023) were the variables independently associated to normalisation of EF., Conclusion: HF with recovered EF is a frequent phenomenon. It has a more favourable clinical course, prognosis and basal characteristics than HF with persistent reduced EF. Further studies are needed to identify natural history and optimal medications for HF-recovered patients., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent syndrome with an elevated risk of morbidity and mortality. To date, there is scarce evidence on the role of peak exercise oxygen uptake (peak VO 2 ) for predicting the morbidity burden in HFpEF. We sought to evaluate the association between peak VO 2 and the risk of recurrent hospitalizations in patients with HFpEF., Methods: A total of 74 stable symptomatic patients with HFpEF underwent a cardiopulmonary exercise test between June 2012 and May 2016. A negative binomial regression method was used to determine the association between the percentage of predicted peak VO 2 (pp-peak VO 2 ) and recurrent hospitalizations. Risk estimates are reported as incidence rate ratios., Results: The mean age was 72.5 ± 9.1 years, 53% were women, and all patients were in New York Heart Association functional class II to III. Mean peak VO 2 and median pp-peak VO 2 were 10 ± 2.8mL/min/kg and 60% (range, 47-67), respectively. During a median follow-up of 276 days [interquartile range, 153-1231], 84 all-cause hospitalizations in 31 patients (41.9%) were registered. A total of 15 (20.3%) deaths were also recorded. On multivariate analysis, accounting for mortality as a terminal event, pp-peak VO 2 was independently and linearly associated with the risk of recurrent admission. Thus, and modeled as continuous, a 10% decrease of pp-peak VO 2 increased the risk of recurrent hospitalizations by 32% (IRR, 1.32; 95%CI, 1.03-1.68; P = .028)., Conclusions: In symptomatic elderly patients with HFpEF, pp-peak VO 2 predicts all-cause recurrent admission., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) presents a major challenge in modern cardiology. Although this syndrome is of increasing prevalence and is associated with unfavorable outcomes, treatment trials have failed to establish effective therapies. Currently, solutions to this dilemma are being investigated, including categorizing and characterizing patients more diversely to individualize treatment. In this regard, new imaging techniques might provide important information. Diastolic dysfunction is a diagnostic and pathophysiological cornerstone in HFpEF and is believed to be caused by systemic inflammation with the development of interstitial myocardial fibrosis and myocardial stiffening. Cardiac magnetic resonance (CMR) T 1 -mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. This review provides an overview of the potential of myocardial tissue characterization with CMR T 1 mapping in HFpEF patients, outlining its diagnostic and prognostic implications and discussing future directions. We conclude that CMR T 1 mapping is potentially an effective tool for patient characterization in large-scale epidemiological, diagnostic, and therapeutic HFpEF trials beyond traditional imaging parameters., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)