Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction.
Ontology highlight
ABSTRACT:
SUBMITTER: Samson R
PROVIDER: S-EPMC4859363 | biostudies-literature | 2016 Jan
REPOSITORIES: biostudies-literature
Publications
Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction.
Samson Rohan R Jaiswal Abhishek A Ennezat Pierre V PV Cassidy Mark M Le Jemtel Thierry H TH
Journal of the American Heart Association 20160125 1
Similar Datasets
Project description:BackgroundComorbidity-driven microvascular inflammation is posited as a unifying pathophysiologic mechanism for heart failure with preserved ejection fraction (HFpEF). Obesity is proinflammatory and common in HFpEF. We hypothesized that unique obesity-inflammation HFpEF phenotypes exist and are associated with differences in clinical features, fibrosis biomarkers, and functional performance.MethodsPatients (n=301) from 3 HFpEF clinical trials were studied. Unsupervised machine learning (hierarchical clustering) with obese status and 13 inflammatory biomarkers as input variables was performed. Associations of clusters with HFpEF severity and fibrosis biomarkers (PIIINP [procollagen III N-terminal peptide], CITP [C-telopeptide for type I collagen], IGFBP7 [insulin-like growth factor-binding protein-7], and GAL-3 [galectin-3]) were assessed.ResultsHierarchical clustering revealed 3 phenotypes: pan-inflammatory (n=129; 64% obese), noninflammatory (n=83; 55% obese), and obese high CRP (C-reactive protein; n=89; 98% obese). The pan-inflammatory phenotype had more comorbidities and heart failure hospitalizations; higher left atrial volume, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and fibrosis biomarkers; and lower glomerular filtration rate, peak oxygen consumption, 6-minute walk distance, and active hours/day (P<0.05 for all). The noninflammatory phenotype had the most favorable values for all measures. The obese high CRP phenotype resembled the noninflammatory phenotype except for isolated elevation of CRP and lower functional performance. Hierarchical cluster assignment was independent of CRP genotype combinations that alter CRP levels and more biologically plausible than other clustering approaches. Multiple traditional analytic techniques confirmed and extended the hierarchical clustering findings.ConclusionsUnique obesity-inflammation phenotypes exist in HFpEF and are associated with differences in comorbidity burden, HFpEF severity, and fibrosis. These data support comorbidity-driven microvascular inflammation as a pathophysiologic mechanism for many but not all HFpEF patients.
| S-EPMC7439286 | 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:Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous collection of conditions that are unified by the presence of a left ventricular ejection fraction ≥50%, evidence of impaired diastolic function and elevated natriuretic peptide levels, all within the context of typical heart failure signs and symptoms. However, while HFpEF is steadily becoming the predominant form of heart failure, disease-modifying treatment options for this population remain sparse. This review provides an overview of the diagnosis, management and prevention of HFpEF for general physicians.
| S-EPMC6334030 | biostudies-literature
Project description:Recent clinical trials in patients with heart failure with preserved ejection fraction (HFpEF) have provided important insights into participant selection strategies. Historically, HFpEF trials have included patients with relatively preserved left ventricular ejection fraction ranging from 40% to 55% and a clinical history of heart failure. Contemporary HFpEF trials have also incorporated inclusion criteria such as hospitalization for HFpEF, altered functional capacity, cardiac structural and functional abnormalities, and abnormalities in neurohormonal status (e.g., elevated natriuretic peptide levels). Careful analyses of the effect of these patient selection criteria on outcomes in prior trials provide valuable lessons for future trial design. We review recent and ongoing HFpEF clinical trials from a patient selection perspective and appraise trial patient selection methodologies in relation to outcomes. This review reflects discussions between clinicians, scientists, trialists, regulators, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum in Paris, France, on December 6, 2013.
| S-EPMC4713836 | biostudies-other
Project description:Despite the burden of heart failure (HF) with preserved ejection fraction (HFpEF), its pathophysiological mechanisms remain controversial and are likely to be multifactorial. Indeed, it has been suggested that HFpEF may represent "a forest of a variety of trees", because of heterogeneity in pathophysiological mechanisms involved and phenotypic expression of the disease. A better understanding of HFpEF is crucial for the development of appropriate therapeutic targets. Recent studies on HFpEF have highlighted its particular haemodynamic features, and haemodynamic derangements are critical to both early and advanced stages of the disease. By definition, haemodynamic properties are determined by the result of the dynamic interchange between the heart, vasculature, and autonomic nervous system, which regulate the circulation of blood. Importantly, it has been shown that both intrinsic and extrinsic factors are implicated in the haemodynamic impairments typical of HFpEF patients. Thus, understanding of HFpEF haemodynamics requires consideration of the interplay between both cardiac and non-cardiac factors.
| S-EPMC5490949 | biostudies-other
Project description:AimsThe aim of this study is to use six previously described heart failure with preserved ejection fraction (HFpEF) phenotypes to describe differences in (i) the biological response to spironolactone, (ii) clinical endpoints, and (iii) patient-reported health status by HFpEF phenotype and treatment arm in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT).Methods and resultsWe analysed 1767 patients in TOPCAT from the Americas. Using 11 clinical variables, patients were classified according to six HFpEF phenotypes previously identified in the I-PRESERVE and CHARM-Preserved studies. Kansas City Cardiomyopathy Questionnaire (KCCQ) measured health status. All phenotypes showed increase in potassium with spironolactone, although only three phenotypes showed significant increase in creatinine, and two phenotypes showed significant decrease in systolic blood pressure. Rate of the TOPCAT primary outcome (cardiovascular death, aborted cardiac arrest, or heart failure hospitalization) differed by HFpEF phenotype (P < 0.001) but not by treatment arm within each HFpEF phenotype. Baseline KCCQ score differed by HFpEF phenotype (P < 0.001), although some phenotypes with poor health status had lower rates of the TOPCAT primary outcome, and some phenotypes with better health status had higher rates of the TOPCAT primary outcome. However, within 3/6 phenotypes, higher baseline KCCQ score was associated with lower risk of the TOPCAT primary outcome. Change in KCCQ scores at 4 and 12 months did not differ among HFpEF phenotypes overall or by treatment arm.ConclusionsComplex, data-driven HFpEF phenotypes differ according to biological response to spironolactone, baseline health status, and clinical endpoints. These differences may inform the design of targeted clinical trials focusing on improvement in outcomes most relevant for specific HFpEF phenotypes.
| S-EPMC7261552 | biostudies-literature
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:Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence as the general population ages. Poorly managed heart failure symptoms of decompensated HFpEF is one of the most common reasons for prolonged hospital admission. The high rate of morbidity and mortality associated with HFpEF is compounded by a poor understanding of the underpinning pathophysiology. Randomized controlled trials have so far been unable to identify an evidence base for reducing morbidity and mortality in patients with HFpEF, although there is some evidence to support quality of life (QOL) improvement. In this review, we described the recent advances on the pathophysiological understanding of HFpEF, the current and emerging treatment strategies, and what this may mean for individual patients. Potential treatments for HFpEF were divided into their relative management strategies and the current evidence assessed for effect on HFpEF mortality, hospital admission frequency, and QOL improvement. Overall, the understanding of HFpEF pathophysiology is improving and has been made a priority in identifying potential therapeutic targets. There is growing evidence that patients with ejection fractions (EF) of less than 60% may obtain a mortality benefit from ACE-inhibitors, angiotensin-neprilysin inhibitors, Angiotensin Receptor Blockers, and Mineralocorticoid Receptor Antagonists. However, this covers only a small proportion of the HFpEF spectrum. Therefore, currently there are no universal treatment strategies recommended for HFpEF, and management should focus on an individualised approach and this should take into account the comorbidities of each patient.
| S-EPMC7186731 | biostudies-literature
Project description:AimsThe aims of this study were to explore phenotypes of heart failure with preserved ejection fraction (HFpEF) and evaluate differential effects of spironolactone treatment.Methods and resultsA swap-stepwise algorithm was used for variable selection. Latent class analysis based on 10 selected variables was employed in a derivative set of 1540 patients from the TOPCAT trial. Cox proportional hazard models were used to evaluate the prognoses and effects of spironolactone treatment. Three phenotypes of HFpEF were identified. Phenotype 1 was the youngest with low burden of co-morbidities. Phenotype 2 was the oldest with high prevalence of atrial fibrillation, pacemaker implantation, and hypothyroidism. Phenotype 3 was mostly obese and diabetic with high burden of other co-morbidities. Compared with phenotype 1, phenotypes 2 (hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.14-1.89; P = 0.003) and 3 (HR: 2.35; 95% CI: 1.80-3.07; P < 0.001) were associated with higher risks of the primary composite outcome. Spironolactone treatment was associated with a reduced risk of the primary outcome only in phenotype 1 (HR: 0.63; 95% CI: 0.40-0.98; P = 0.042).ConclusionsThree distinct HFpEF phenotypes were identified. Spironolactone treatment could improve clinical outcome in a phenotype of relatively young patients with low burden of co-morbidities.
| S-EPMC9288804 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) accounts for ~50% of all heart failure cases. HFpEF is a heterogeneous condition with poorly understood molecular mechanisms related to different forms including acute and chronic HFpEF. Here, we utilised plasma samples collected from patients with different forms of HFpEF to identify unique molecular mechanisms and pathways. We performed unbiased, comprehensive proteomic analyses of 31 gender- and BMI-matched plasma samples from patients with acute HFpEF (n=8), chronic HFpEF (n=9) and hypertrophic cardiomyopathy (HCM; n=14). We identified leucine-rich alpha-2-glycoprotein 1 (LRG1) as an aberrant protein across all three forms of HFpEF. We reported perturbations in signalling pathways in HFpEF mainly driven by complement/coagulation/protease and extracellular matrix (ECM) proteins, highlighting the haemostatic disturbances, notably platelet degranulation caused by systematically elevated platelet cytosolic Ca2+. We provided a publicly available online application (https://hao-chen-uts-99171821.shinyapps.io/HFpEF-Proteomics/) of our findings.
2023-03-11 | PXD024012 | Pride