Prognosis of "pre-heart failure" clinical phenotypes.
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ABSTRACT:
SUBMITTER: Velagaleti RS
PROVIDER: S-EPMC7147998 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesThis study sought to assess if clinical phenogroups differ in comprehensive biomarker profiles, cardiac and arterial structure/function, and responses to spironolactone therapy.BackgroundPrevious studies identified distinct subgroups (phenogroups) of patients with heart failure with preserved ejection fraction (HFpEF).MethodsAmong TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial) participants, we performed latent-class analysis to identify HFpEF phenogroups based on standard clinical features and assessed differences in multiple biomarkers measured from frozen plasma; cardiac and arterial structure/function measured with echocardiography and arterial tonometry; prognosis; and response to spironolactone.ResultsThree HFpEF phenogroups were identified. Phenogroup 1 (n = 1,214) exhibited younger age, higher prevalence of smoking, preserved functional class, and the least evidence of left ventricular (LV) hypertrophy and arterial stiffness. Phenogroup 2 (n = 1,329) was older, with normotrophic concentric LV remodeling, atrial fibrillation, left atrial enlargement, large-artery stiffening, and biomarkers of innate immunity and vascular calcification. Phenogroup 3 (n = 899) demonstrated more functional impairment, obesity, diabetes, chronic kidney disease, concentric LV hypertrophy, high renin, and biomarkers of tumor necrosis factor-alpha-mediated inflammation, liver fibrosis, and tissue remodeling. Compared with phenogroup 1, phenogroup 3 exhibited the highest risk of the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest (hazard ratio [HR]: 3.44; 95% confidence interval [CI]: 2.79 to 4.24); phenogroups 2 and 3 demonstrated similar all-cause mortality (phenotype 2 HR: 2.36; 95% CI: 1.89 to 2.95; phenotype 3 HR: 2.26, 95% CI: 1.77 to 2.87). Spironolactone randomized therapy was associated with a more pronounced reduction in the risk of the primary endpoint in phenogroup 3 (HR: 0.75; 95% CI: 0.59 to 0.95; p for interaction = 0.016). Results were similar after excluding participants from Eastern Europe.ConclusionsWe identified important differences in circulating biomarkers, cardiac/arterial characteristics, prognosis, and response to spironolactone across clinical HFpEF phenogroups. These findings suggest distinct underlying mechanisms across clinically identifiable phenogroups of HFpEF that may benefit from different targeted interventions.
| S-EPMC7058514 | biostudies-literature
Project description: Not available
| S-EPMC4859363 | biostudies-literature
Project description:Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.
| S-EPMC11023004 | biostudies-literature
Project description:BACKGROUND: There are limited data describing how pre-existing heart failure affects mortality following pneumonia. OBJECTIVE: To examine the association between history and severity of heart failure and mortality among patients hospitalized for pneumonia. DESIGN: Population-based cohort study in Western Denmark between 1994 and 2003. PATIENTS: 33,736 adults with a first-time hospitalization for pneumonia. Heart failure was identified and categorized based on data linked from population-based health care databases. MEASUREMENTS: We compared 30-day mortality between patients with pre-existing heart failure and other pneumonia patients, while adjusting for age, gender, comorbidity, and medication use. RESULTS: The 30-day mortality was 24.4% among heart-failure patients and 14.4% among other patients, with an adjusted 30-day mortality rate ratio (MRR) of 1.40 (95% CI: 1.29-1.51). Adjusted MRRs increased according to severity of pre-existing heart failure, as indicated by medication regimen: thiazide-based, MRR = 1.09 (95% CI: 0.79-1.50); loop-diuretics, MRR = 1.25 (95% CI: 1.10-1.43); loop-diuretics and digoxin, MRR = 1.35 (95% CI: 1.18-1.55); loop-diuretics and spironolactone, MRR = 1.72 (95% CI: 1.49-2.00). Pre-existing heart valve disease and atrial fibrillation substantially increased mortality. CONCLUSION: History and severity of heart failure are associated with a poor outcome for patients hospitalized with pneumonia.
| S-EPMC2517996 | biostudies-other
Project description:Classification of chronic heart failure (HF) is on the basis of criteria that may not adequately capture disease heterogeneity. Improved phenotyping may help inform research and therapeutic strategies.This study used cluster analysis to explore clinical phenotypes in chronic HF patients.A cluster analysis was performed on 45 baseline clinical variables from 1,619 participants in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) study, which evaluated exercise training versus usual care in chronic systolic HF. An association between identified clusters and clinical outcomes was assessed using Cox proportional hazards modeling. Differential associations between clinical outcomes and exercise testing were examined using interaction testing.Four clusters were identified (ranging from 248 to 773 patients in each), in which patients varied considerably among measures of age, sex, race, symptoms, comorbidities, HF etiology, socioeconomic status, quality of life, cardiopulmonary exercise testing parameters, and biomarker levels. Differential associations were observed for hospitalization and mortality risks between and within clusters. Compared with cluster 1, risk of all-cause mortality and/or all-cause hospitalization ranged from 0.65 (95% confidence interval [95% CI]: 0.54 to 0.78) for cluster 4 to 1.02 (95% CI: 0.87 to 1.19) for cluster 3. However, for all-cause mortality, cluster 3 had a disproportionately lower risk of 0.61 (95% CI: 0.44 to 0.86). Evidence suggested differential effects of exercise treatment on changes in peak oxygen consumption and clinical outcomes between clusters (p for interaction <0.04).Cluster analysis of clinical variables identified 4 distinct phenotypes of chronic HF. Our findings underscore the high degree of disease heterogeneity that exists within chronic HF patients and the need for improved phenotyping of the syndrome. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).
| S-EPMC4254424 | biostudies-literature
Project description:Chronic heart failure (HF) is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF) and HF with preserved left ventricular ejection fraction (HFpEF). Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF.
| S-EPMC4909708 | biostudies-literature
Project description:AimsWe documented the midterm prognosis of left ventricular thrombus (LVT) in heart failure (HF) patients with dilated cardiomyopathy (DCM) and ischaemic cardiomyopathy (ICM). We aimed to characterize patients with LVT in the context of HF with reduced (≤40%) left ventricular ejection fraction and evaluate their risk for death and/or embolic events, overall, and specifically in patients with ischaemic or non-ischaemic aetiology. We also intended to identify risk factors for LVT in patients with DCM.Methods and resultsWe included all HF patients (N = 105, age 56 ± 13) admitted from 2005 to 2018 in our institution for LVT without significant valve disease/prosthesis, heart transplant/left ventricular assist device, congenital heart disease, or acute myocardial infarction. Our primary endpoint was the 1 year risk of the composite of all-cause mortality (ACM) and symptomatic embolic events. Mean left ventricular ejection fraction was 23 ± 9%, and median BNP was 1795 pg/mL. Most (97%) patients were treated with vitamin K anticoagulants, and 64% had ICM. Symptomatic embolic events and/or ACM occurred in 20% of the population [embolic events (all within 30 days of LVT diagnosis) 15% and ACM 6%] and was similarly frequent in DCM or ICM (P > 0.05). Suspected/transient embolic events were more frequent in DCM (overall 13%; 29% in DCM vs. 5% in ICM, P < 0.01). Major bleeding occurred in 5% of patients. Left ventricular reverse remodelling occurred in 65% of patients, more frequently in DCM (86% in DCM vs. 65% in ICM, P = 0.02). In a case-control analysis matching DCM patients, BNP level was the only factor significantly associated with LVT (2447 pg/mL in LVT vs. 347 pg/mL, P < 0.001).ConclusionsPatients with LVT have markedly high natriuretic peptides and experience a 20% 1 year risk for embolic events and/or death following diagnosis despite anticoagulant treatment. Most patients have favourable remodelling/recovery. As all symptomatic embolic events occurred within 30 days of LVT diagnosis, a very careful initial management is warranted.
| S-EPMC8006720 | biostudies-literature
Project description:Patients with acute heart failure (AHF) are included into clinical trials regardless of differences in baseline clinical characteristics. The aim of this study was to assess patients with AHF according to the presence of central and/or peripheral congestion at hospital admission and evaluate treatment response and outcomes in studied phenotypes. We investigated retrospectively 352 patients (mean age: 68 ± 13 years, 77% men) hospitalized due to AHF with the signs of congestion on admission. Patients were divided according to the type of signs of congestion into three groups: A, isolated pulmonary congestion (n = 52, 15%); B, isolated peripheral congestion (n = 31, 9%); and C, signs of mixed (peripheral and central) congestion (n = 269, 76%). Patients from Group A had lower concentration of urea, bilirubin, and gamma-glutamyl transferase whereas higher level of haematocrit, albumin, and leukocytes on admission. The highest baseline N-terminal pro-B-type natriuretic peptide level (median: 4113 vs. 3634 vs. 6093 pg/mL) and percentage of patients with chronic heart failure (56 vs. 58 vs. 74%; A vs. B. vs. C, respectively, all P < 0.01) were observed in Group C. There were no differences in terms of demographics, co-morbidities, left ventricular ejection fraction, and applied treatment between studied groups. Patients from Group A had the highest systolic blood pressure on admission (145 ± 37 vs. 122 ± 20 vs. 130 ± 29 mmHg) and the biggest decrease in systolic blood pressure [-22 (-45 to -4) vs. -2 (-13 to 2) vs. -10 (-25 to 0) mmHg] and heart rate [-16 (-35 to -1.5) vs. -1 (-10 to 5) vs. -7 (-20 to 0) b.p.m.] with the lowest weight change [-1.0 (-1.0 to 0) vs. -2.9 (-3.8 to -0.9) vs. -2.0 (-3.0 to -1.0) kg; all P < 0.01] after 48 h of hospitalization. There were differences in short-term and long-term outcomes with favourable results in Group A. Group A experienced less frequent in-hospital heart failure worsening during the first 48 h (4 vs. 23 vs. 7%), had shorter length of hospital stay [6 (5-8) vs. 7 (5-11) vs. 7 (6-11) days], and had lower 1 year all-cause mortality (12 vs. 28 vs. 29%; all P < 0.05). Presence of peripheral congestion on admission was independent predictor for all-cause mortality within 1 year [hazard ratio (95% confidence interval): 2.68 (1.06-6.79); P = 0.04]. Patterns of congestion in AHF are associated with differences in clinical characteristics, treatment response, and outcomes. It needs to be considered once planning clinical trials in AHF.
| S-EPMC7754722 | biostudies-literature
Project description:At least one-half of the growing heart failure population consists of heart failure with preserved ejection fraction (HFpEF). The limited therapeutic options, the complexity of the syndrome, and many related comorbidities emphasize the need for adequate experimental animal models to study the etiology of HFpEF, as well as its comorbidities and pathophysiological changes. The strengths and weaknesses of available animal models have been reviewed extensively with the general consensus that a "1-size-fits-all" model does not exist, because no uniform HFpEF patient exists. In fact, HFpEF patients have been categorized into HFpEF phenogroups based on comorbidities and symptoms. In this review, we therefore study which animal model is best suited to study the different phenogroups-to improve model selection and refinement of animal research. Based on the published data, we extrapolated human HFpEF phenogroups into 3 animal phenogroups (containing small and large animals) based on reports and definitions of the authors: animal models with high (cardiac) age (phenogroup aging); animal models focusing on hypertension and kidney dysfunction (phenogroup hypertension/kidney failure); and models with hypertension, obesity, and type 2 diabetes mellitus (phenogroup cardiometabolic syndrome). We subsequently evaluated characteristics of HFpEF, such as left ventricular diastolic dysfunction parameters, systemic inflammation, cardiac fibrosis, and sex-specificity in the different models. Finally, we scored these parameters concluded how to best apply these models. Based on our findings, we propose an easy-to-use classification for future animal research based on clinical phenogroups of interest.
| S-EPMC9436760 | biostudies-literature
Project description:Monocytes are a heterogeneous population of effector cells with key roles in tissue integrity restoration and maintenance. Here, we explore the association of monocyte subsets and prognosis in patients with ambulatory heart failure (HF). Monocyte subsets were classified as classical (CD14++/CD16-), intermediate (CD14++/CD16+), or non-classical (CD14+/CD16++). Percentage distribution and absolute cell count were assessed in each subset, and multivariable Cox regression analyses were performed with all-cause death, HF-related hospitalization, and the composite end-point of both as dependent variables. 400 patients were consecutively included (72.8% male, age 69.4±12.2 years, 45.5% from ischemic aetiology, left ventricle ejection fraction (LVEF) 41.6% ±14.5, New York Heart Association (NYHA) class II 62.8% and III 30.8%). During a mean follow-up of 2.6±0.9 years, 107 patients died, 99 had a HF-related hospitalization and 160 suffered the composite end-point of all-cause death or HF-related hospitalization. Monocyte subsets assessed in percentages were not independently associated to any of the end-points. When considering number of cells/μL, intermediate subset was independently associated with an increase of all-cause death (HR 1.25 [95% CI 1,02-1.52], p = 0.03), and the composite end-point HR 1.20 [95% CI 1,03-1.40], p = 0.02). The presented findings show that absolute cell count of monocyte subsets was preferred over monocyte percentage for prognosis stratification for outpatients with HF. The intermediate monocyte subset provides information on increased risk of all-cause death and the composite end-point.
| S-EPMC6150659 | biostudies-literature